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Sample records for ada regulatory locus

  1. Regulatory organization of the staphylococcal sae locus.

    PubMed

    Adhikari, Rajan P; Novick, Richard P

    2008-03-01

    This paper describes an investigation of the complex internal regulatory circuitry of the staphylococcal sae locus and the impact of modifying this circuitry on the expression of external genes in the sae regulon. The sae locus contains four genes, the saeR and S two-component signalling module (TCS), and saeP and Q, two upstream genes of hitherto unknown function. It is expressed from two promoters, P(A)sae, which transcribes only the TCS, and P(C)sae, which transcribes the entire locus. A bursa aurealis (bursa) transposon insertion in saeP in a derivative of Staphylococcus aureus NCTC 8325 has a profound effect on sae function. It modifies the activity of the TCS, changing the expression of many genes in the sae regulon, even though transcription of the TCS (from P(A)sae) is not interrupted. Moreover, these effects are not due to disruption of saeP since an in-frame deletion in saeP has essentially no phenotype. The phenotype of S. aureus strain Newman is remarkably similar to that of the saeP : : bursa and this similarity is explained by an amino acid substitution in the Newman saeS gene that is predicted to modify profoundly the signalling function of the protein. This concurrence suggests that the saeP : : bursa insertion affects the signalling function of saeS, a suggestion that is supported by the ability of an saeQR clone, but not an saeR clone, to complement the effects of the saeP : : bursa insertion.

  2. The IgH locus 3' regulatory region: pulling the strings from behind.

    PubMed

    Pinaud, Eric; Marquet, Marie; Fiancette, Rémi; Péron, Sophie; Vincent-Fabert, Christelle; Denizot, Yves; Cogné, Michel

    2011-01-01

    Antigen receptor gene loci are among the most complex in mammals. The IgH locus, encoding the immunoglobulin heavy chain (IgH) in B-lineage cells, undergoes major transcription-dependent DNA remodeling events, namely V(D)J recombination, Ig class-switch recombination (CSR), and somatic hypermutation (SHM). Various cis-regulatory elements (encompassing promoters, enhancers, and chromatin insulators) recruit multiple nuclear factors in order to ensure IgH locus regulation by tightly orchestrated physical and/or functional interactions. Among major IgH cis-acting regions, the large 3' regulatory region (3'RR) located at the 3' boundary of the locus includes several enhancers and harbors an intriguing quasi-palindromic structure. In this review, we report progress insights made over the past decade in order to describe in more details the structure and functions of IgH 3'RRs in mouse and human. Generation of multiple cellular, transgenic and knock-out models helped out to decipher the function of the IgH 3' regulatory elements in the context of normal and pathologic B cells. Beside its interest in physiology, the challenge of elucidating the locus-wide cross talk between distant cis-regulatory elements might provide useful insights into the mechanisms that mediate oncogene deregulation after chromosomal translocations onto the IgH locus.

  3. Induction of resistance to alkylating agents in E. coli: the ada+ gene product serves both as a regulatory protein and as an enzyme for repair of mutagenic damage.

    PubMed Central

    Teo, I; Sedgwick, B; Demple, B; Li, B; Lindahl, T

    1984-01-01

    The expression of several inducible enzymes for repair of alkylated DNA in Escherichia coli is controlled by the ada+ gene. This regulatory gene has been cloned into a multicopy plasmid and shown to code for a 37-kd protein. Antibodies raised against homogeneous O6-methylguanine-DNA methyltransferase (the main repair activity for mutagenic damage in alkylated DNA) were found to cross-react with this 37-kd protein. Cell extracts from several independently derived ada mutants contain variable amounts of an altered 37-kd protein after an inducing alkylation treatment. In addition, an 18-kd protein identical with the previously isolated O6-methyl-guanine-DNA methyltransferase has been identified as a product of the ada+ gene. The smaller polypeptide is derived from the 37-kd protein by proteolytic processing. Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6092060

  4. The adenovirus E1A protein targets the SAGA but not the ADA transcriptional regulatory complex through multiple independent domains.

    PubMed

    Shuen, Michael; Avvakumov, Nikita; Walfish, Paul G; Brandl, Chris J; Mymryk, Joe S

    2002-08-23

    Expression of the adenovirus E1A protein in the simple eukaryote Saccharomyces cerevisiae inhibits growth. We tested four regions of E1A that alter growth and transcription in mammalian cells for their effects in yeast when expressed as fusions to the Gal4p DNA binding domain. Expression of the N-terminal/conserved region (CR) 1 or CR3, but not of the CR2 or the C-terminal portion of E1A, inhibited yeast growth. Growth inhibition was relieved by deletion of the genes encoding the yGcn5p, Ngg1p, or Spt7p components of the SAGA transcriptional regulatory complex, but not the Ahc1p component of the related ADA complex, indicating that the N-terminal/CR1 and CR3 regions of E1A target the SAGA complex independently. Expression of the pCAF acetyltransferase, a mammalian homologue of yGcn5p, also suppressed growth inhibition by either portion of E1A. Furthermore, the N-terminal 29 residues and the CR3 portion of E1A interacted independently with yGcn5p and pCAF in vitro. Thus, two separate regions of E1A target the yGcn5p component of the SAGA transcriptional activation complex. A subregion of the N-terminal/CR1 fragment spanning residues 30-69 within CR1 also inhibited yeast growth in a SAGA-dependent fashion. However, this region did not interact with yGcn5p or pCAF, suggesting that it makes a third contact with another SAGA component. Our results provide a new model system to elucidate mechanisms by which E1A and the SAGA complex regulate transcription and growth. PMID:12070146

  5. Scrutinizing the FTO locus: compelling evidence for a complex, long-range regulatory context.

    PubMed

    Rask-Andersen, Mathias; Almén, Markus Sällman; Schiöth, Helgi B

    2015-11-01

    Single nucleotide polymorphisms (SNPs) within a genetic region including the first two introns of the gene encoding FTO have consistently been shown to be the strongest genetic factors influencing body mass index (BMI). However, this same also contains several regulatory DNA elements that affect the expression of IRX3 and IRX5, which respectively, are located approximately 500 kb and 1.2 Mbp downstream from the BMI-associated FTO locus. Through these affected regulatory elements, genetic variation at the FTO locus influences adipocyte development leading to decreased thermogenesis and increased lipid storage. These findings provide a genomic model for the functional implications of genetic variations at this locus, and also demonstrate the importance of accounting for chromatin-chromatin interactions when constructing hypotheses for the mechanisms of trait and disease-associated common genetic variants. Several consortia have generated genome-wide datasets describing different aspects of chromatin biology which can be utilized to predict functionality and propose biologically relevant descriptions of specific DNA regions. Here, we review some of the publically available data resources on genome function and organization that can be used to gain an overview of genetic regions of interest and to generate testable hypotheses for future studies. We use the BMI- and obesity-associated FTO locus as a subject as it poses an illustrative example on the value of these resources. We find that public databases strongly support long-range interactions between regulatory elements in the FTO locus with the IRXB cluster genes IRX3 and IRX5. Chromatin configuration capture data also support interactions across a large region stretching across from the RPGRIP1L gene, FTO and the IRXB gene cluster. PMID:26340902

  6. Epigenetic Regulation of Individual Modules of the immunoglobulin heavy chain locus 3′ Regulatory Region

    PubMed Central

    Birshtein, Barbara K.

    2014-01-01

    The Igh locus undergoes an amazing array of DNA rearrangements and modifications during B cell development. During early stages, the variable region gene is constructed from constituent variable (V), diversity (D), and joining (J) segments (VDJ joining). B cells that successfully express an antibody can be activated, leading to somatic hypermutation (SHM) focused on the variable region, and class switch recombination (CSR), which substitutes downstream constant region genes for the originally used Cμ constant region gene. Many investigators, ourselves included, have sought to understand how these processes specifically target the Igh locus and avoid other loci and potential deleterious consequences of malignant transformation. Our laboratory has concentrated on a complex regulatory region (RR) that is located downstream of Cα, the most 3′ of the Igh constant region genes. The ~40 kb 3′ RR, which is predicted to serve as a downstream major regulator of the Igh locus, contains two distinct segments: an ~28 kb region comprising four enhancers, and an adjacent ~12 kb region containing multiple CTCF and Pax5 binding sites. Analysis of targeted mutations in mice by a number of investigators has concluded that the entire 3′ RR enhancer region is essential for SHM and CSR (but not for VDJ joining) and for high levels of expression of multiple isotypes. The CTCF/Pax5 binding region is a candidate for influencing VDJ joining early in B cell development and serving as a potential insulator of the Igh locus. Components of the 3′ RR are subject to a variety of epigenetic changes during B cell development, i.e., DNAse I hypersensitivity, histone modifications, and DNA methylation, in association with transcription factor binding. I propose that these changes provide a foundation by which regulatory elements in modules of the 3′ RR function by interacting with each other and with target sequences of the Igh locus. PMID:24795714

  7. Epigenetic Regulation of Individual Modules of the immunoglobulin heavy chain locus 3' Regulatory Region.

    PubMed

    Birshtein, Barbara K

    2014-01-01

    The Igh locus undergoes an amazing array of DNA rearrangements and modifications during B cell development. During early stages, the variable region gene is constructed from constituent variable (V), diversity (D), and joining (J) segments (VDJ joining). B cells that successfully express an antibody can be activated, leading to somatic hypermutation (SHM) focused on the variable region, and class switch recombination (CSR), which substitutes downstream constant region genes for the originally used Cμ constant region gene. Many investigators, ourselves included, have sought to understand how these processes specifically target the Igh locus and avoid other loci and potential deleterious consequences of malignant transformation. Our laboratory has concentrated on a complex regulatory region (RR) that is located downstream of Cα, the most 3' of the Igh constant region genes. The ~40 kb 3' RR, which is predicted to serve as a downstream major regulator of the Igh locus, contains two distinct segments: an ~28 kb region comprising four enhancers, and an adjacent ~12 kb region containing multiple CTCF and Pax5 binding sites. Analysis of targeted mutations in mice by a number of investigators has concluded that the entire 3' RR enhancer region is essential for SHM and CSR (but not for VDJ joining) and for high levels of expression of multiple isotypes. The CTCF/Pax5 binding region is a candidate for influencing VDJ joining early in B cell development and serving as a potential insulator of the Igh locus. Components of the 3' RR are subject to a variety of epigenetic changes during B cell development, i.e., DNAse I hypersensitivity, histone modifications, and DNA methylation, in association with transcription factor binding. I propose that these changes provide a foundation by which regulatory elements in modules of the 3' RR function by interacting with each other and with target sequences of the Igh locus.

  8. Pleiotropic regulatory locus 2 exhibits unequal genetic redundancy with its homolog PRL1.

    PubMed

    Weihmann, Tabea; Palma, Kristoffer; Nitta, Yukino; Li, Xin

    2012-09-01

    In plants, signaling leading to resistance against biotrophic pathogens is complex. Perception of pathogenic microbes by resistance (R) proteins is relayed though successive activities of downstream components, in a network that is not well understood. PLEIOTROPIC REGULATORY LOCUS 1 (PRL1) and >20 other proteins are members of the MOS4-associated complex (MAC), a regulatory node in defense signaling. Of all characterized MAC members, mutations in PRL1 cause the most severe susceptibility towards both virulent and avirulent microbial pathogens. Genetic suppressors of prl1 represent new signaling elements and may aid in further unraveling of defense mechanisms. Our identification and characterization of a dominant suppressor of prl1 revealed a regulatory, gain-of-function mutation in PLEIOTROPIC REGULATORY LOCUS 2 (PRL2), a close homolog of PRL1. Loss-of-function mutants of PRL2 do not exhibit altered phenotypes; however, prl1 prl2 double mutants exhibit enhanced morphological defects consistent with unequal genetic redundancy between the homologs. Up-regulated gene expression mediated by the dominant prl2-1D allele completely suppresses disease susceptibility in the prl1 mutant background and also restores wild-type appearance, further supporting functional equivalence between the two PRL proteins. PMID:22813545

  9. Epigenetic allelic states of a maize transcriptional regulatory locus exhibit overdominant gene action.

    PubMed Central

    Hollick, J B; Chandler, V L

    1998-01-01

    Using alleles of the maize purple plant locus (pl), which encodes a transcriptional regulator of anthocyanin pigment synthesis, we describe a case of single-locus heterosis, or overdominance, where the heterozygote displays a phenotype that is greater than either homozygote. The Pl-Rhoades (Pl-Rh) allele is subject to epigenetic changes in gene expression, resulting in quantitatively distinct expression states. Allelic states with low-expression levels, designated Pl'-mahogany (Pl'-mah), are dominant to the high-expression state of Pl-Rh. Pl'-mah states retain low-expression levels in subsequent generations when homozygous or heterozygous with Pl-Rh. However, Pl'-mah alleles frequently exhibit higher expression levels when heterozygous with other pl alleles; illustrating an overdominant allelic relationship. Higher expression levels are also observed when Pl'-mah is hemizygous. These results suggest that persistent allelic interactions between Pl'-mah and Pl-Rh are required to maintain the low-expression state and that other pl alleles are missing sequences required for this interaction. The Pl-Rh state can be sexually transmitted from Pl'-mah/pl heterozygotes, but not from Pl'-mah hemizygotes, suggesting that fixation of the high-expression state may involve synapsis. The existence of such allele-dependent regulatory mechanisms implicates a novel importance of allele polymorphisms in the genesis and maintenance of genetic variation. PMID:9755217

  10. Ada issues in implementing ART-Ada

    NASA Technical Reports Server (NTRS)

    Lee, S. Daniel

    1990-01-01

    Due to the Ada mandate of a number of government agencies, interest in deploying expert systems such as Ada has increased. Recently, several Ada-based expert system tools have been developed. According to a recent benchmark report, these tools do not perform as well as similar tools written in C. While poorly implemented Ada compilers contribute to the poor benchmark result, some fundamental problems of the Ada language itself have been uncovered. Here, the authors describe Ada language issues encountered during the deployment of ART-Ada, an expert system tool for Ada deployment. ART-Ada is being used to implement several prototype expert systems for the Space Station Freedom and the U.S. Air Force.

  11. The 3’-Jα Region of the TCRα Locus Bears Gene Regulatory Activity in Thymic and Peripheral T Cells

    PubMed Central

    Kučerová-Levisohn, Martina; Knirr, Stefan; Mejia, Rosa I.; Ortiz, Benjamin D.

    2015-01-01

    Much progress has been made in understanding the important cis-mediated controls on mouse TCRα gene function, including identification of the Eα enhancer and TCRα locus control region (LCR). Nevertheless, previous data have suggested that other cis-regulatory elements may reside in the locus outside of the Eα/LCR. Based on prior findings, we hypothesized the existence of gene regulatory elements in a 3.9-kb region 5’ of the Cα exons. Using DNase hypersensitivity assays and TCRα BAC reporter transgenes in mice, we detected gene regulatory activity within this 3.9-kb region. This region is active in both thymic and peripheral T cells, and selectively affects upstream, but not downstream, gene expression. Together, these data indicate the existence of a novel cis-acting regulatory complex that contributes to TCRα transgene expression in vivo. The active chromatin sites we discovered within this region would remain in the locus after TCRα gene rearrangement, and thus may contribute to endogenous TCRα gene activity, particularly in peripheral T cells, where the Eα element has been found to be inactive. PMID:26177549

  12. Locus-wide identification of EGR2/Krox20 regulatory targets in myelin genes

    PubMed Central

    Jang, Sung-Wook; Srinivasan, Rajini; Jones, Erin A.; Sun, Guannan; Keles, Sunduz; Krueger, Courtney; Chang, Li-Wei; Nagarajan, Rakesh; Svaren, John

    2011-01-01

    Myelination of peripheral nerves by Schwann cells depends upon a gene regulatory network controlled by Egr2/Krox20, which is specifically required for Schwann cells to initiate and maintain myelination. To elucidate the mechanism by which Egr2 regulates gene expression during myelination, we have performed chromatin immunoprecipitation analysis on myelinating rat sciatic nerve in vivo. The resulting samples were applied to a tiled microarray consisting of a broad spectrum of genes that are activated or repressed in Egr2-deficient mice. The results show extensive binding within myelin-associated genes, as well as some genes that become repressed in myelinating Schwann cells. Many of the Egr2 peaks coincide with regions of open chromatin, which is a marker of enhancer regions. In addition, further analysis showed that there is substantial colocalization of Egr2 binding with Sox10, a transcription factor required for Schwann cell specification and other stages of Schwann cell development. Finally, we have found that Egr2 binds to promoters of several lipid biosynthetic genes, which is consistent with their dramatic upregulation during the formation of lipid-rich myelin. Overall, this analysis provides a locus-wide profile of Egr2 binding patterns in major myelin-associated genes using myelinating peripheral nerve. PMID:21044070

  13. Transforming AdaPT to Ada

    NASA Technical Reports Server (NTRS)

    Goldsack, Stephen J.; Holzbach-Valero, A. A.; Waldrop, Raymond S.; Volz, Richard A.

    1991-01-01

    This paper describes how the main features of the proposed Ada language extensions intended to support distribution, and offered as possible solutions for Ada9X can be implemented by transformation into standard Ada83. We start by summarizing the features proposed in a paper (Gargaro et al, 1990) which constitutes the definition of the extensions. For convenience we have called the language in its modified form AdaPT which might be interpreted as Ada with partitions. These features were carefully chosen to provide support for the construction of executable modules for execution in nodes of a network of loosely coupled computers, but flexibly configurable for different network architectures and for recovery following failure, or adapting to mode changes. The intention in their design was to provide extensions which would not impact adversely on the normal use of Ada, and would fit well in style and feel with the existing standard. We begin by summarizing the features introduced in AdaPT.

  14. Identification and Potential Regulatory Properties of Evolutionary Conserved Regions (ECRs) at the Schizophrenia-Associated MIR137 Locus.

    PubMed

    Gianfrancesco, Olympia; Griffiths, Daniel; Myers, Paul; Collier, David A; Bubb, Vivien J; Quinn, John P

    2016-10-01

    Genome-wide association studies (GWAS) have identified a region at chromosome 1p21.3, containing the microRNA MIR137, to be among the most significant associations for schizophrenia. However, the mechanism by which genetic variation at this locus increases risk of schizophrenia is unknown. Identifying key regulatory regions around MIR137 is crucial to understanding the potential role of this gene in the aetiology of psychiatric disorders. Through alignment of vertebrate genomes, we identified seven non-coding regions at the MIR137 locus with conservation comparable to exons (>70 %). Bioinformatic analysis using the Psychiatric Genomics Consortium GWAS dataset for schizophrenia showed five of the ECRs to have genome-wide significant SNPs in or adjacent to their sequence. Analysis of available datasets on chromatin marks and histone modification data showed that three of the ECRs were predicted to be functional in the human brain, and three in development. In vitro analysis of ECR activity using reporter gene assays showed that all seven of the selected ECRs displayed transcriptional regulatory activity in the SH-SY5Y neuroblastoma cell line. This data suggests a regulatory role in the developing and adult brain for these highly conserved regions at the MIR137 schizophrenia-associated locus and further that these domains could act individually or synergistically to regulate levels of MIR137 expression. PMID:27525637

  15. Classic-Ada(TM)

    NASA Technical Reports Server (NTRS)

    Valley, Lois

    1989-01-01

    The SPS product, Classic-Ada, is a software tool that supports object-oriented Ada programming with powerful inheritance and dynamic binding. Object Oriented Design (OOD) is an easy, natural development paradigm, but it is not supported by Ada. Following the DOD Ada mandate, SPS developed Classic-Ada to provide a tool which supports OOD and implements code in Ada. It consists of a design language, a code generator and a toolset. As a design language, Classic-Ada supports the object-oriented principles of information hiding, data abstraction, dynamic binding, and inheritance. It also supports natural reuse and incremental development through inheritance, code factoring, and Ada, Classic-Ada, dynamic binding and static binding in the same program. Only nine new constructs were added to Ada to provide object-oriented design capabilities. The Classic-Ada code generator translates user application code into fully compliant, ready-to-run, standard Ada. The Classic-Ada toolset is fully supported by SPS and consists of an object generator, a builder, a dictionary manager, and a reporter. Demonstrations of Classic-Ada and the Classic-Ada Browser were given at the workshop.

  16. Molecular characterization of aflR, a regulatory locus for aflatoxin biosynthesis.

    PubMed Central

    Woloshuk, C P; Foutz, K R; Brewer, J F; Bhatnagar, D; Cleveland, T E; Payne, G A

    1994-01-01

    Aflatoxins belong to a family of decaketides that are produced as secondary metabolites by Aspergillus flavus and A. parasiticus. The aflatoxin biosynthetic pathway involves several enzymatic steps that appear to be regulated by the afl2 gene in A. flavus and the apa2 gene in A. parasiticus. Several lines of evidence indicate that these two genes are homologous. The DNA sequences of the two genes are highly similar, they both are involved in the regulation of aflatoxin biosynthesis, and apa2 can complement the afl2 mutation in A. flavus. Because of these similarities, we propose that these two genes are homologs, and because of the ability of these genes to regulate aflatoxin biosynthesis, we suggest that they be designated aflR. We report here the further characterization of aflR from A. flavus and show that aflR codes for a 2,078-bp transcript with an open reading frame of 1,311 nucleotides that codes for 437 amino acids and a putative protein of 46,679 daltons. Analysis of the predicted amino acid sequence indicated that the polypeptide contains a zinc cluster motif between amino acid positions 29 and 56. This region contains the consensus sequence Cys-Xaa2-Cys-Xaa6-Cys-Xaa6-Cys-Xaa2-Cys-Xaa6+ ++-Cys. This motif has been found in several fungal transcriptional regulatory proteins. DNA hybridization of the aflR gene with genomic digests of seven polyketide-producing fungi revealed similar sequences in three other species related to A. flavus: A. parasiticus, A. oryzae, and A. sojae. Finally, we present evidence for an antisense transcript (aflRas) derived from the opposite strand of aflR, suggesting that the aflR locus involves some form of antisense regulation. Images PMID:8074521

  17. Genomic position effects lead to an inefficient reorganization of nucleosomes in the 5'-regulatory region of the chicken lysozyme locus in transgenic mice.

    PubMed Central

    Huber, M C; Krüger, G; Bonifer, C

    1996-01-01

    The chicken lysozyme locus is gradually activated during macrophage development exhibiting a specific chromatin structure with each differentiation state. Its small size and the extensive characterization of its cis-regulatory elements allows us to study even subtle changes in chromatin structure of the entire gene locus during transcriptional activation. Tissue-specific and position independent expression of the lysozyme locus in transgenic mice requires the cooperation of all cis-regulatory elements. In order to elucidate further the molecular basis of locus activation, we have determined nucleosome positions within the complete 5'-regulatory region of the chicken lysozyme locus in chicken myeloid cell lines and transgenic mice. Each cis-regulatory element develops its unique nucleosomal structure and each one remodels chromatin differently. The nucleosomal organization of the endogenous gene in chicken cell lines and the transgene in the mouse turned out to be identical, enabling us to study the influence of cis-regulatory deletions on the development of an active chromatin structure in transgenic mice. Transgenes with a deletion of an important cis-regulatory element show an impediment in nucleosome reorganization as compared with the complete lysozyme locus. We demonstrate that multicopy transgene-clusters in position dependently expressing mouse lines exhibit a heterogeneous chromatin organization. PMID:8628676

  18. ADA Restroom Design.

    ERIC Educational Resources Information Center

    Rittner-Heir, Robbin M.

    2000-01-01

    Discusses the challenges that the Americans with Disabilities Act (ADA) creates for designing school restrooms. The issues of mobility and circulation of users are addressed. Some of the dimension requirements required by the ADA are listed. (GR)

  19. Multiple Hepatic Regulatory Variants at the GALNT2 GWAS Locus Associated with High-Density Lipoprotein Cholesterol

    PubMed Central

    Roman, Tamara S.; Marvelle, Amanda F.; Fogarty, Marie P.; Vadlamudi, Swarooparani; Gonzalez, Arlene J.; Buchkovich, Martin L.; Huyghe, Jeroen R.; Fuchsberger, Christian; Jackson, Anne U.; Wu, Ying; Civelek, Mete; Lusis, Aldons J.; Gaulton, Kyle J.; Sethupathy, Praveen; Kangas, Antti J.; Soininen, Pasi; Ala-Korpela, Mika; Kuusisto, Johanna; Collins, Francis S.; Laakso, Markku; Boehnke, Michael; Mohlke, Karen L.

    2015-01-01

    Genome-wide association studies (GWASs) have identified more than 150 loci associated with blood lipid and cholesterol levels; however, the functional and molecular mechanisms for many associations are unknown. We examined the functional regulatory effects of candidate variants at the GALNT2 locus associated with high-density lipoprotein cholesterol (HDL-C). Fine-mapping and conditional analyses in the METSIM study identified a single locus harboring 25 noncoding variants (r2 > 0.7 with the lead GWAS variants) strongly associated with total cholesterol in medium-sized HDL (e.g., rs17315646, p = 3.5 × 10−12). We used luciferase reporter assays in HepG2 cells to test all 25 variants for allelic differences in regulatory enhancer activity. rs2281721 showed allelic differences in transcriptional activity (75-fold [T] versus 27-fold [C] more than the empty-vector control), as did a separate 780-bp segment containing rs4846913, rs2144300, and rs6143660 (49-fold [AT– haplotype] versus 16-fold [CC+ haplotype] more). Using electrophoretic mobility shift assays, we observed differential CEBPB binding to rs4846913, and we confirmed this binding in a native chromatin context by performing chromatin-immunoprecipitation (ChIP) assays in HepG2 and Huh-7 cell lines of differing genotypes. Additionally, sequence reads in HepG2 DNase-I-hypersensitivity and CEBPB ChIP-seq signals spanning rs4846913 showed significant allelic imbalance. Allelic-expression-imbalance assays performed with RNA from primary human hepatocyte samples and expression-quantitative-trait-locus (eQTL) data in human subcutaneous adipose tissue samples confirmed that alleles associated with increased HDL-C are associated with a modest increase in GALNT2 expression. Together, these data suggest that at least rs4846913 and rs2281721 play key roles in influencing GALNT2 expression at this HDL-C locus. PMID:26637976

  20. Multiple Hepatic Regulatory Variants at the GALNT2 GWAS Locus Associated with High-Density Lipoprotein Cholesterol.

    PubMed

    Roman, Tamara S; Marvelle, Amanda F; Fogarty, Marie P; Vadlamudi, Swarooparani; Gonzalez, Arlene J; Buchkovich, Martin L; Huyghe, Jeroen R; Fuchsberger, Christian; Jackson, Anne U; Wu, Ying; Civelek, Mete; Lusis, Aldons J; Gaulton, Kyle J; Sethupathy, Praveen; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Kuusisto, Johanna; Collins, Francis S; Laakso, Markku; Boehnke, Michael; Mohlke, Karen L

    2015-12-01

    Genome-wide association studies (GWASs) have identified more than 150 loci associated with blood lipid and cholesterol levels; however, the functional and molecular mechanisms for many associations are unknown. We examined the functional regulatory effects of candidate variants at the GALNT2 locus associated with high-density lipoprotein cholesterol (HDL-C). Fine-mapping and conditional analyses in the METSIM study identified a single locus harboring 25 noncoding variants (r(2) > 0.7 with the lead GWAS variants) strongly associated with total cholesterol in medium-sized HDL (e.g., rs17315646, p = 3.5 × 10(-12)). We used luciferase reporter assays in HepG2 cells to test all 25 variants for allelic differences in regulatory enhancer activity. rs2281721 showed allelic differences in transcriptional activity (75-fold [T] versus 27-fold [C] more than the empty-vector control), as did a separate 780-bp segment containing rs4846913, rs2144300, and rs6143660 (49-fold [AT(-) haplotype] versus 16-fold [CC(+) haplotype] more). Using electrophoretic mobility shift assays, we observed differential CEBPB binding to rs4846913, and we confirmed this binding in a native chromatin context by performing chromatin-immunoprecipitation (ChIP) assays in HepG2 and Huh-7 cell lines of differing genotypes. Additionally, sequence reads in HepG2 DNase-I-hypersensitivity and CEBPB ChIP-seq signals spanning rs4846913 showed significant allelic imbalance. Allelic-expression-imbalance assays performed with RNA from primary human hepatocyte samples and expression-quantitative-trait-locus (eQTL) data in human subcutaneous adipose tissue samples confirmed that alleles associated with increased HDL-C are associated with a modest increase in GALNT2 expression. Together, these data suggest that at least rs4846913 and rs2281721 play key roles in influencing GALNT2 expression at this HDL-C locus. PMID:26637976

  1. ART/Ada and CLIPS/Ada

    NASA Technical Reports Server (NTRS)

    Culbert, Chris

    1990-01-01

    Although they have reached a point of commercial viability, expert systems were originally developed in artificial intelligence (AI) research environments. Many of the available tools still work best in such environments. These environments typically utilize special hardware such as LISP machines and relatively unfamiliar languages such as LISP or Prolog. Space Station applications will require deep integration of expert system technology with applications developed in conventional languages, specifically Ada. The ability to apply automation to Space Station functions could be greatly enhanced by widespread availability of state-of-the-art expert system tools based on Ada. Although there have been some efforts to examine the use of Ada for AI applications, there are few, if any, existing products which provide state-of-the-art AI capabilities in an Ada tool. The goal of the ART/Ada Design Project is to conduct research into the implementation in Ada of state-of-the-art hybrid expert systems building tools (ESBT's). This project takes the following approach: using the existing design of the ART-IM ESBT as a starting point, analyze the impact of the Ada language and Ada development methodologies on that design; redesign the system in Ada; and analyze its performance. The research project will attempt to achieve a comprehensive understanding of the potential for embedding expert systems in Ada systems for eventual application in future Space Station Freedom projects. During Phase 1 of the project, initial requirements analysis, design, and implementation of the kernel subset of ART-IM functionality was completed. During Phase 2, the effort has been focused on the implementation and performance analysis of several versions with increasing functionality. Since production quality ART/Ada tools will not be available for a considerable time, and additional subtask of this project will be the completion of an Ada version of the CLIPS expert system shell developed by NASA

  2. New cis-regulatory elements in the Rht-D1b locus region of wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fifteen gene-containing BACs with accumulated length of 1.82-Mb from the Rht-D1b locus region weresequenced and compared in detail with the orthologous regions of rice, sorghum, and maize. Our results show that Rht-D1b represents a conserved genomic region as implied by high gene sequence identity...

  3. Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus

    PubMed Central

    Yang, Rui; Kerschner, Jenny L.; Gosalia, Nehal; Neems, Daniel; Gorsic, Lidija K.; Safi, Alexias; Crawford, Gregory E.; Kosak, Steven T.; Leir, Shih-Hsing; Harris, Ann

    2016-01-01

    Higher order chromatin structure establishes domains that organize the genome and coordinate gene expression. However, the molecular mechanisms controlling transcription of individual loci within a topological domain (TAD) are not fully understood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene provides a paradigm for investigating these mechanisms. CFTR occupies a TAD bordered by CTCF/cohesin binding sites within which are cell-type-selective cis-regulatory elements for the locus. We showed previously that intronic and extragenic enhancers, when occupied by specific transcription factors, are recruited to the CFTR promoter by a looping mechanism to drive gene expression. Here we use a combination of CRISPR/Cas9 editing of cis-regulatory elements and siRNA-mediated depletion of architectural proteins to determine the relative contribution of structural elements and enhancers to the higher order structure and expression of the CFTR locus. We found the boundaries of the CFTR TAD are conserved among diverse cell types and are dependent on CTCF and cohesin complex. Removal of an upstream CTCF-binding insulator alters the interaction profile, but has little effect on CFTR expression. Within the TAD, intronic enhancers recruit cell-type selective transcription factors and deletion of a pivotal enhancer element dramatically decreases CFTR expression, but has minor effect on its 3D structure. PMID:26673704

  4. Managing Ada development

    NASA Technical Reports Server (NTRS)

    Green, James R.

    1986-01-01

    The Ada programming language was developed under the sponsorship of the Department of Defense to address the soaring costs associated with software development and maintenance. Ada is powerful, and yet to take full advantage of its power, it is sufficiently complex and different from current programming approaches that there is considerable risk associated with committing a program to be done in Ada. There are also few programs of any substantial size that have been implemented using Ada that may be studied to determine those management methods that resulted in a successful Ada project. The items presented are the author's opinions which have been formed as a result of going through an experience software development. The difficulties faced, risks assumed, management methods applied, and lessons learned, and most importantly, the techniques that were successful are all valuable sources of management information for those managers ready to assume major Ada developments projects.

  5. Experiments with Ada

    NASA Technical Reports Server (NTRS)

    Roy, D.; Mcclimens, M.; Agresti, W.

    1985-01-01

    A 1200-line Ada source code project simulating the most basic functions of an operations control center was developed. We selected George Cherry's Process Abstraction Methodology for Embedded Large Applications (PAMELA) and DEC's Ada Compilation System (ACS) under VAX/VMS to build the software from requirements to acceptance test. The system runs faster than its FORTRAN implementation and was produced on schedule and under budget with an overall productivity in excess of 30 lines of Ada source code per day.

  6. Righting the ADA

    ERIC Educational Resources Information Center

    National Council on Disability, 2004

    2004-01-01

    Many Americans with disabilities feel that a series of negative court decisions is reducing their status to that of "second-class citizens," a status that the Americans with Disabilities Act (ADA) was supposed to remedy forever. In this report, the National Council on Disability (NCD), which first proposed the enactment of an ADA and developed the…

  7. Nucleotide sequence of the regulatory locus controlling expression of bacterial genes for bioluminescence.

    PubMed Central

    Engebrecht, J; Silverman, M

    1987-01-01

    Production of light by the marine bacterium Vibrio fischeri and by recombinant hosts containing cloned lux genes is controlled by the density of the culture. Density-dependent regulation of lux gene expression has been shown to require a locus consisting of the luxR and luxI genes and two closely linked divergent promoters. As part of a genetic analysis to understand the regulation of bioluminescence, we have sequenced the region of DNA containing this control circuit. Open reading frames corresponding to luxR and luxI were identified; transcription start sites were defined by S1 nuclease mapping and sequences resembling promoter elements were located. Images PMID:3697093

  8. The HAP3 regulatory locus of Saccharomyces cerevisiae encodes divergent overlapping transcripts.

    PubMed Central

    Hahn, S; Pinkham, J; Wei, R; Miller, R; Guarente, L

    1988-01-01

    Activation of the CYC1 upstream activation site, UAS2, and transcription of several other genes encoding respiratory functions requires the product of the regulatory gene HAP2. We report here the isolation and characterization of a second UAS2 regulatory gene, HAP3. Like mutations in HAP2, a mutation in HAP3 abolishes the activity of UAS2 and prevents growth on nonfermentable carbon sources. The HAP3 gene was cloned and, surprisingly, was found to encode two divergently transcribed, overlapping transcripts: a 570-base RNA and a 3-kilobase (kb) RNA. Chromosomal disruption experiments defined the critical region for HAP3 function to a 1.3-kb segment in which the two transcripts overlap. Analysis of the HAP3 DNA sequence showed that the 570-base transcript could encode a protein of 144 amino acids. Synthesis of the 144-amino-acid protein under regulatory control in vivo demonstrated that this protein is essential for activity of UAS2 as well as for growth on nonfermentable carbon sources. The largest open reading frame in the critical region of the 3-kb transcript is only 86 amino acids. Using site-directed mutagenesis, we demonstrated that the 86-amino-acid open reading frame was not involved in UAS2 activity. The possible role of this 3-kb antisense RNA in HAP3 expression or function is discussed. Images PMID:2832732

  9. Transposon tagging and molecular analysis of the maize regulatory locus opaque-2

    SciTech Connect

    Schmidt, R.J.; Burr, F.A.; Burr, B.

    1987-11-13

    Genetic analyses suggested that the opaque-2 (o2) locus in maize acts as a positive, transacting, transcriptional activator of the zein seed storage-protein genes. Because isolation of the gene is requisite to understanding the molecular details of this regulation, transposon mutagensis with the transposable element suppressor-mutator (Spm) was carried out, and three mutable o2 alleles were obtained. One of these alleles contained an 8.3-kilobase autonomous Spm, another a 6.8-kilobase nonautonomous Spm, and the third an unidentified transposon that is unrelated to Spm. A DNA sequence flanking the autonomous Spm insertion was verified to be o2-specific and provided a probe to clone a wild-type allele. Northern blots indicated that the gene is expressed in wild-type endosperm but not in leaf tissues or in endosperms homozygous for a mutant allele of the O2 gene. A transcript was detected in endosperms homozygous for mutations at opaque-7 and floury-2, an indication that O2 expression is independent of these two other putative regulators of zein synthesis.

  10. Deploying expert systems in Ada

    NASA Technical Reports Server (NTRS)

    Lee, S. Daniel; Allen, Bradley P.

    1989-01-01

    As the Department of Defense Ada mandate begins to be enforced actively, interest in deploying expert systems in Ada has increased. A prototype Ada based expert system tool is introduced called ART/Ada. This prototype was built to support research into the language and operational issues of expert systems in Ada. ART/Ada allows applications of a conventional expert system tool called ART-IM (Automated Reasoning Tool for Information Management) to be deployed in various Ada environments with efficient use of time and space. ART-IM, a C-based expert system tool, is used to generate Ada source code which is compiled and linked with an Ada base inference engine to produce an Ada executable image. ART/Ada will be used to implement several prototype expert systems for the Space Station Freedom Program testbeds.

  11. Software engineering capability for Ada (GRASP/Ada Tool)

    NASA Technical Reports Server (NTRS)

    Cross, James H., II

    1995-01-01

    The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada Source code. A new Motif compliant graphical user interface has been developed for the GRASP/Ada prototype.

  12. Regulatory elements necessary for termination of transcription within the immunoglobulin heavy chain gene locus

    SciTech Connect

    Moore, B.B.

    1992-01-01

    Previous experimentation demonstrated that regulation of the IgM only phenotype in both pre-B and immature B cells was primarily at the transcriptional level. Expression of IgD mRNA involves transcription of the entire 29 kilobase rearranged [mu]-[delta] locus. Mature B cells transcribe the [beta] exons at approximately half the level that they transcribe the [delta] gene. Early B cells however, transcribe the [mu] gene with approximately 90% more efficiency than they do the [delta] gene. Specifically, early B cells show a transcription termination event occurring within a 1 kilobase region of the [mu]-[delta] intron. This dissertation analyzes the sequence elements necessary to encode the transcription termination event within the [mu]-[delta] intron. This work shows that the termination motif consists of specific sequences within the [mu]m poly(A) site as well as a region of the [mu]-[delta] intron contained within a 1200 base pair fragment. The 1200 base pair fragment extends from the Pst I site within the intron and ends just prior to the C[delta]1 exon. This fragment contains a 162 base pair unique sequence inverted repeat (USIR). Furthermore, the [mu]m site is specifically required because the [mu]s site was unable to substitute, despite extensive usage. In addition, the USIR-containing intron functions in an orientation-dependent manner. Analysis of this termination motif in a variety of lymphoid and non-lymphoid cells suggests that this motif is an intrinsic polymerase II termination motif. This implies that transcription termination in early B cells is by a default model and that active regulation of this motif involves an anti-termination event in mature B cells.

  13. ART-Ada: An Ada-based expert system tool

    NASA Technical Reports Server (NTRS)

    Lee, S. Daniel; Allen, Bradley P.

    1990-01-01

    The Department of Defense mandate to standardize on Ada as the language for software systems development has resulted in an increased interest in making expert systems technology readily available in Ada environments. NASA's Space Station Freedom is an example of the large Ada software development projects that will require expert systems in the 1990's. Another large scale application that can benefit from Ada based expert system tool technology is the Pilot's Associate (PA) expert system project for military combat aircraft. The Automated Reasoning Tool-Ada (ART-Ada), an Ada expert system tool, is explained. ART-Ada allows applications of a C-based expert system tool called ART-IM to be deployed in various Ada environments. ART-Ada is being used to implement several prototype expert systems for NASA's Space Station Freedom program and the U.S. Air Force.

  14. A survey of ancient conserved non-coding elements in the PAX6 locus reveals a landscape of interdigitated cis-regulatory archipelagos.

    PubMed

    Bhatia, Shipra; Monahan, Jack; Ravi, Vydianathan; Gautier, Philippe; Murdoch, Emma; Brenner, Sydney; van Heyningen, Veronica; Venkatesh, Byrappa; Kleinjan, Dirk A

    2014-03-15

    Biological differences between cell types and developmental processes are characterised by differences in gene expression profiles. Gene-distal enhancers are key components of the regulatory networks that specify the tissue-specific expression patterns driving embryonic development and cell fate decisions, and variations in their sequences are a major contributor to genetic disease and disease susceptibility. Despite advances in the methods for discovery of putative cis-regulatory sequences, characterisation of their spatio-temporal enhancer activities in a mammalian model system remains a major bottle-neck. We employed a strategy that combines gnathostome sequence conservation with transgenic mouse and zebrafish reporter assays to survey the genomic locus of the developmental control gene PAX6 for the presence of novel cis-regulatory elements. Sequence comparison between human and the cartilaginous elephant shark (Callorhinchus milii) revealed several ancient gnathostome conserved non-coding elements (agCNEs) dispersed widely throughout the PAX6 locus, extending the range of the known PAX6 cis-regulatory landscape to contain the full upstream PAX6-RCN1 intergenic region. Our data indicates that ancient conserved regulatory sequences can be tested effectively in transgenic zebrafish even when not conserved in zebrafish themselves. The strategy also allows efficient dissection of compound regulatory regions previously assessed in transgenic mice. Remarkable overlap in expression patterns driven by sets of agCNEs indicates that PAX6 resides in a landscape of multiple tissue-specific regulatory archipelagos. PMID:24440152

  15. Cis-regulatory Changes at FLOWERING LOCUS T Mediate Natural Variation in Flowering Responses of Arabidopsis thaliana

    PubMed Central

    Schwartz, Christopher; Balasubramanian, Sureshkumar; Warthmann, Norman; Michael, Todd P.; Lempe, Janne; Sureshkumar, Sridevi; Kobayashi, Yasushi; Maloof, Julin N.; Borevitz, Justin O.; Chory, Joanne; Weigel, Detlef

    2009-01-01

    Flowering time, a critical adaptive trait, is modulated by several environmental cues. These external signals converge on a small set of genes that in turn mediate the flowering response. Mutant analysis and subsequent molecular studies have revealed that one of these integrator genes, FLOWERING LOCUS T (FT), responds to photoperiod and temperature cues, two environmental parameters that greatly influence flowering time. As the central player in the transition to flowering, the protein coding sequence of FT and its function are highly conserved across species. Using QTL mapping with a new advanced intercross-recombinant inbred line (AI-RIL) population, we show that a QTL tightly linked to FT contributes to natural variation in the flowering response to the combined effects of photoperiod and ambient temperature. Using heterogeneous inbred families (HIF) and introgression lines, we fine map the QTL to a 6.7 kb fragment in the FT promoter. We confirm by quantitative complementation that FT has differential activity in the two parental strains. Further support for FT underlying the QTL comes from a new approach, quantitative knockdown with artificial microRNAs (amiRNAs). Consistent with the causal sequence polymorphism being in the promoter, we find that the QTL affects FT expression. Taken together, these results indicate that allelic variation at pathway integrator genes such as FT can underlie phenotypic variability and that this may be achieved through cis-regulatory changes. PMID:19652183

  16. ART-Ada: An Ada-based expert system tool

    NASA Technical Reports Server (NTRS)

    Lee, S. Daniel; Allen, Bradley P.

    1991-01-01

    The Department of Defense mandate to standardize on Ada as the language for software systems development has resulted in increased interest in making expert systems technology readily available in Ada environments. NASA's Space Station Freedom is an example of the large Ada software development projects that will require expert systems in the 1990's. Another large scale application that can benefit from Ada based expert system tool technology is the Pilot's Associate (PA) expert system project for military combat aircraft. Automated Reasoning Tool (ART) Ada, an Ada Expert system tool is described. ART-Ada allow applications of a C-based expert system tool called ART-IM to be deployed in various Ada environments. ART-Ada is being used to implement several prototype expert systems for NASA's Space Station Freedom Program and the U.S. Air Force.

  17. Identification of the Staphylococcus aureus vfrAB Operon, a Novel Virulence Factor Regulatory Locus

    PubMed Central

    Daly, Seth M.; Hall, Pamela R.; Bayles, Kenneth W.

    2014-01-01

    During a screen of the Nebraska Transposon Mutant Library, we identified 71 mutations in the Staphylococcus aureus genome that altered hemolysis on blood agar medium. Although many of these mutations disrupted genes known to affect the production of alpha-hemolysin, two of them were associated with an apparent operon, designated vfrAB, that had not been characterized previously. Interestingly, a ΔvfrB mutant exhibited only minor effects on the transcription of the hla gene, encoding alpha-hemolysin, when grown in broth, as well as on RNAIII, a posttranscriptional regulatory RNA important for alpha-hemolysin translation, suggesting that VfrB may function at the posttranscriptional level. Indeed, a ΔvfrB mutant had increased aur and sspAB protease expression under these conditions. However, disruption of the known secreted proteases in the ΔvfrB mutant did not restore hemolytic activity in the ΔvfrB mutant on blood agar. Further analysis revealed that, in contrast to the minor effects of VfrB on hla transcription when strains were cultured in liquid media, the level of hla transcription was decreased 50-fold in the absence of VfrB on solid media. These results demonstrate that while VfrB represses protease expression when strains are grown in broth, hla regulation is highly responsive to factors associated with growth on solid media. Intriguingly, the ΔvfrB mutant displayed increased pathogenesis in a model of S. aureus dermonecrosis, further highlighting the complexity of VfrB-dependent virulence regulation. The results of this study describe a phenotype associated with a class of highly conserved yet uncharacterized proteins found in Gram-positive bacteria, and they shed new light on the regulation of virulence factors necessary for S. aureus pathogenesis. PMID:24549328

  18. Identification of the Staphylococcus aureus vfrAB operon, a novel virulence factor regulatory locus.

    PubMed

    Bose, Jeffrey L; Daly, Seth M; Hall, Pamela R; Bayles, Kenneth W

    2014-05-01

    During a screen of the Nebraska Transposon Mutant Library, we identified 71 mutations in the Staphylococcus aureus genome that altered hemolysis on blood agar medium. Although many of these mutations disrupted genes known to affect the production of alpha-hemolysin, two of them were associated with an apparent operon, designated vfrAB, that had not been characterized previously. Interestingly, a ΔvfrB mutant exhibited only minor effects on the transcription of the hla gene, encoding alpha-hemolysin, when grown in broth, as well as on RNAIII, a posttranscriptional regulatory RNA important for alpha-hemolysin translation, suggesting that VfrB may function at the posttranscriptional level. Indeed, a ΔvfrB mutant had increased aur and sspAB protease expression under these conditions. However, disruption of the known secreted proteases in the ΔvfrB mutant did not restore hemolytic activity in the ΔvfrB mutant on blood agar. Further analysis revealed that, in contrast to the minor effects of VfrB on hla transcription when strains were cultured in liquid media, the level of hla transcription was decreased 50-fold in the absence of VfrB on solid media. These results demonstrate that while VfrB represses protease expression when strains are grown in broth, hla regulation is highly responsive to factors associated with growth on solid media. Intriguingly, the ΔvfrB mutant displayed increased pathogenesis in a model of S. aureus dermonecrosis, further highlighting the complexity of VfrB-dependent virulence regulation. The results of this study describe a phenotype associated with a class of highly conserved yet uncharacterized proteins found in Gram-positive bacteria, and they shed new light on the regulation of virulence factors necessary for S. aureus pathogenesis. PMID:24549328

  19. DNA sequence and translational product of a new nodulation-regulatory locus: syrM has sequence similarity to NodD proteins.

    PubMed Central

    Barnett, M J; Long, S R

    1990-01-01

    Rhizobium meliloti nodulation (nod) genes are expressed when activated by trans-acting proteins in the NodD family. The nodD1 and nodD2 gene products activate nod promoters when cells are exposed to plant-synthesized signal molecules. Alternatively, the same nod promoters are activated by the nodD3 gene when nodD3 is carried in trans along with a closely linked global regulatory locus, syrM (symbiotic regulator) (J. T. Mulligan and S. R. Long, Genetics 122:7-18, 1989). In this article we report the nucleotide sequence of a 2.6-kilobase SphI fragment from R. meliloti SU47 containing syrM. Expression from this locus was confirmed by using in vitro transcription-translation assays. The open reading frame encoded a protein of either 33 or 36 kilodaltons whose sequence shows similarity to NodD regulatory proteins. Images PMID:2361944

  20. Parallel programming with Ada

    SciTech Connect

    Kok, J.

    1988-01-01

    To the human programmer the ease of coding distributed computing is highly dependent on the suitability of the employed programming language. But with a particular language it is also important whether the possibilities of one or more parallel architectures can efficiently be addressed by available language constructs. In this paper the possibilities are discussed of the high-level language Ada and in particular of its tasking concept as a descriptional tool for the design and implementation of numerical and other algorithms that allow execution of parts in parallel. Language tools are explained and their use for common applications is shown. Conclusions are drawn about the usefulness of several Ada concepts.

  1. A LISP-Ada connection

    NASA Technical Reports Server (NTRS)

    Jaworski, Allan; Lavallee, David; Zoch, David

    1987-01-01

    The prototype demonstrates the feasibility of using Ada for expert systems and the implementation of an expert-friendly interface which supports knowledge entry. In the Ford LISP-Ada Connection (FLAC) system LISP and Ada are used in ways which complement their respective capabilities. Future investigation will concentrate on the enhancement of the expert knowledge entry/debugging interface and on the issues associated with multitasking and real-time expert systems implementation in Ada.

  2. Benchmark Lisp And Ada Programs

    NASA Technical Reports Server (NTRS)

    Davis, Gloria; Galant, David; Lim, Raymond; Stutz, John; Gibson, J.; Raghavan, B.; Cheesema, P.; Taylor, W.

    1992-01-01

    Suite of nonparallel benchmark programs, ELAPSE, designed for three tests: comparing efficiency of computer processing via Lisp vs. Ada; comparing efficiencies of several computers processing via Lisp; or comparing several computers processing via Ada. Tests efficiency which computer executes routines in each language. Available for computer equipped with validated Ada compiler and/or Common Lisp system.

  3. AN ADA NAMELIST PACKAGE

    NASA Technical Reports Server (NTRS)

    Klumpp, A. R.

    1994-01-01

    The Ada Namelist Package, developed for the Ada programming language, enables a calling program to read and write FORTRAN-style namelist files. A namelist file consists of any number of assignment statements in any order. Features of the Ada Namelist Package are: the handling of any combination of user-defined types; the ability to read vectors, matrices, and slices of vectors and matrices; the handling of mismatches between variables in the namelist file and those in the programmed list of namelist variables; and the ability to avoid searching the entire input file for each variable. The principle user benefits of this software are the following: the ability to write namelist-readable files, the ability to detect most file errors in the initialization phase, a package organization that reduces the number of instantiated units to a few packages rather than to many subprograms, a reduced number of restrictions, and an increased execution speed. The Ada Namelist reads data from an input file into variables declared within a user program. It then writes data from the user program to an output file, printer, or display. The input file contains a sequence of assignment statements in arbitrary order. The output is in namelist-readable form. There is a one-to-one correspondence between namelist I/O statements executed in the user program and variables read or written. Nevertheless, in the input file, mismatches are allowed between assignment statements in the file and the namelist read procedure statements in the user program. The Ada Namelist Package itself is non-generic. However, it has a group of nested generic packages following the nongeneric opening portion. The opening portion declares a variety of useraccessible constants, variables and subprograms. The subprograms are procedures for initializing namelists for reading, reading and writing strings. The subprograms are also functions for analyzing the content of the current dataset and diagnosing errors. Two nested

  4. Flanking regulatory sequences of the locus encoding the murine GDNF receptor, c-ret, directs lac Z (beta-galactosidase) expression in developing somatosensory system.

    PubMed

    Sukumaran, M; Waxman, S G; Wood, J N; Pachnis, V

    2001-11-01

    RET forms the catalytic component within the receptor complex that transmits signals from the GDNF family of neurotrophic factors. To study the mechanisms regulating the cell-type specific expression of this gene, we have cloned and characterised the murine c-ret locus. A cosmid contig comprising approximately 60 kb of the mouse genome encompassing the entire structural gene and flanking sequences have been isolated and the transcription initiation site identified and promoter characterised. The murine c-ret promoter lacks a TATA initiation motif and has GC enriched DNA sequences reminiscent of CpG islands. Analysis of transgenic mice lines bearing the Lac Z (beta-galactosidase) reporter gene under the control of 5' flanking sequences show modularity in the organisation of cis-regulatory domains within the locus. Cloned 5' flanking sequences comprise a distal regulatory domain directing Lac Z expression at the primitive streak, lateral mesoderm and facial ganglia and a proximal sensory neurones specific regulatory domain inducing Lac Z expression primarily within the developing somatosensory system. The spatial and temporal progression of transgene expression precisely recapitulates endogenous gene expression in developing sensory ganglia including its induction in postnatal Isolectin B4 binding nociceptive neurones. PMID:11747074

  5. Distribution, evolution, and diversity of retrotransposons at the flamenco locus reflect the regulatory properties of piRNA clusters.

    PubMed

    Zanni, Vanessa; Eymery, Angéline; Coiffet, Michael; Zytnicki, Matthias; Luyten, Isabelle; Quesneville, Hadi; Vaury, Chantal; Jensen, Silke

    2013-12-01

    Most of our understanding of Drosophila heterochromatin structure and evolution has come from the annotation of heterochromatin from the isogenic y; cn bw sp strain. However, almost nothing is known about the heterochromatin's structural dynamics and evolution. Here, we focus on a 180-kb heterochromatic locus producing Piwi-interacting RNAs (piRNA cluster), the flamenco (flam) locus, known to be responsible for the control of at least three transposable elements (TEs). We report its detailed structure in three different Drosophila lines chosen according to their capacity to repress or not to repress the expression of two retrotransposons named ZAM and Idefix, and we show that they display high structural diversity. Numerous rearrangements due to homologous and nonhomologous recombination, deletions and segmental duplications, and loss and gain of TEs are diverse sources of active genomic variation at this locus. Notably, we evidence a correlation between the presence of ZAM and Idefix in this piRNA cluster and their silencing. They are absent from flam in the strain where they are derepressed. We show that, unexpectedly, more than half of the flam locus results from recent TE insertions and that most of the elements concerned are prone to horizontal transfer between species of the melanogaster subgroup. We build a model showing how such high and constant dynamics of a piRNA master locus open the way to continual emergence of new patterns of piRNA biogenesis leading to changes in the level of transposition control. PMID:24248389

  6. ADAS Update and Maintainability

    NASA Technical Reports Server (NTRS)

    Watson, Leela R.

    2010-01-01

    Since 2000, both the National Weather Service Melbourne (NWS MLB) and the Spaceflight Meteorology Group (SMG) have used a local data integration system (LOIS) as part of their forecast and warning operations. The original LOIS was developed by the Applied Meteorology Unit (AMU) in 1998 (Manobianco and Case 1998) and has undergone subsequent improvements. Each has benefited from three-dimensional (3-D) analyses that are delivered to forecasters every 15 minutes across the peninsula of Florida. The intent is to generate products that enhance short-range weather forecasts issued in support of NWS MLB and SMG operational requirements within East Central Florida. The current LDIS uses the Advanced Regional Prediction System (ARPS) Data Analysis System (AD AS) package as its core, which integrates a wide variety of national, regional, and local observational data sets. It assimilates all available real-time data within its domain and is run at a finer spatial and temporal resolution than current national or regional-scale analysis packages. As such, it provides local forecasters with a more comprehensive understanding of evolving fine-scale weather features. Over the years, the LDIS has become problematic to maintain since it depends on AMU-developed shell scripts that were written for an earlier version of the ADAS software. The goals of this task were to update the NWS MLB/SMG LDIS with the latest version of ADAS, incorporate new sources of observational data, and upgrade and modify the AMU-developed shell scripts written to govern the system. In addition, the previously developed ADAS graphical user interface (GUI) was updated. Operationally, these upgrades will result in more accurate depictions of the current local environment to help with short-range weather forecasting applications, while also offering an improved initialization for local versions of the Weather Research and Forecasting (WRF) model used by both groups.

  7. AdaNET executive summary

    NASA Technical Reports Server (NTRS)

    Digman, R. Michael

    1988-01-01

    The goal of AdaNET is to transfer existing and emerging software engineering technology from the Federal government to the private sector. The views and perspectives of the current project participants on long and short term goals for AdaNET; organizational structure; resources and returns; summary of identified AdaNET services; and the summary of the organizational model currently under discussion are presented.

  8. Ada training evaluation and recommendation

    NASA Technical Reports Server (NTRS)

    Murphy, Robert; Stark, Michael

    1987-01-01

    This paper documents the Ada training experiences and recommendations of the Gamma Ray Observatory dynamics simulator Ada development team. A two month Ada training program for software developers is recommended which stresses the importance of teaching design methodologies early, as well as the use of certain training aids such as videotaped lectures and computer-aided instruction. Furthermore, a separate training program for managers is recommended, so that they may gain a better understanding of modified review products and resource allocation associated with Ada projects.

  9. AdaNET research project

    NASA Technical Reports Server (NTRS)

    Digman, R. Michael

    1988-01-01

    The components necessary for the success of the commercialization of an Ada Technology Transition Network are reported in detail. The organizational plan presents the planned structure for services development and technical transition of AdaNET services to potential user communities. The Business Plan is the operational plan for the AdaNET service as a commercial venture. The Technical Plan is the plan from which the AdaNET can be designed including detailed requirements analysis. Also contained is an analysis of user fees and charges, and a proposed user fee schedule.

  10. Introduction to Image Algebra Ada

    NASA Astrophysics Data System (ADS)

    Wilson, Joseph N.

    1991-07-01

    Image Algebra Ada (IAA) is a superset of the Ada programming language designed to support use of the Air Force Armament Laboratory's image algebra in the development of computer vision application programs. The IAA language differs from other computer vision languages is several respects. It is machine independent, and an IAA translator has been implemented in the military standard Ada language. Its image operands and operations can be used to program a range of both low- and high-level vision algorithms. This paper provides an overview of the image algebra constructs supported in IAA and describes the embodiment of these constructs in the IAA extension of Ada. Examples showing the use of IAA for a range of computer vision tasks are given. The design of IAA as a superset of Ada and the implementation of the initial translator in Ada represent critical choices. The authors discuss the reasoning behind these choices as well as the benefits and drawbacks associated with them. Implementation strategies associated with the use of Ada as an implementation language for IAA are also discussed. While one can look on IAA as a program design language (PDL) for specifying Ada programs, it is useful to consider IAA as a separate language superset of Ada. This admits the possibility of directly translating IAA for implementation on special purpose architectures. This paper explores strategies for porting IAA to various architectures and notes the critical language and implementation features for porting to different architectures.

  11. Transforming AdaPT to Ada9x

    NASA Technical Reports Server (NTRS)

    Goldsack, Stephen J.; Holzbach-Valero, A. A.; Volz, Richard A.; Waldrop, Raymond S.

    1993-01-01

    How the concepts of AdaPT can be transformed into programs using the object oriented features proposed in the preliminary mapping for Ada9x are described. Emphasizing, as they do, the importance of data types as units of program, these features match well with the development of partitions as translations into Abstract Data Types which was exploited in the Ada83 translation covered in report R3. By providing a form of polymorphic type, the Ada83 version also gives support for the conformant partition idea which could be achieved in Ada83 only by using UNCHECKED CONVERSIONS. It is assumed that the reader understands AdaPT itself, but the translation into Ada83 is briefly reviewed, by applying it to a small example. This is then used to show how the same translation would be achieved in the 9x version. It is important to appreciate that the distribution features which are proposed in current mapping are not used or discussed in any detail, as those are not well matched to the AdaPT approach. Critical evaluation and comparison of these approaches is given in a separate report.

  12. Update of GRASP/Ada reverse engineering tools for Ada

    NASA Technical Reports Server (NTRS)

    Cross, James H., II

    1992-01-01

    The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped a new algorithmic level graphical representation of Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under VMS on a VAS 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented using the HP widget toolkit and the X Windows System. In Phase 3, the user interface was extensively reworked using the Athena widget toolkit and X Windows. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. Following Phase 3, the prototype was evaluated by software engineering students at Auburn University and then updated with significant enhancements to the user interface including editing capabilities. Version 3.2 of the prototype was prepared for limited distribution to facilitate further evaluation. The current prototype provides the capability for the user to generate CSD's from Ada PDL or source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical application.

  13. Using Ada: The deeper challenges

    NASA Technical Reports Server (NTRS)

    Feinberg, David A.

    1986-01-01

    The Ada programming language and the associated Ada Programming Support Environment (APSE) and Ada Run Time Environment (ARTE) provide the potential for significant life-cycle cost reductions in computer software development and maintenance activities. The Ada programming language itself is standardized, trademarked, and controlled via formal validation procedures. Though compilers are not yet production-ready as most would desire, the technology for constructing them is sufficiently well known and understood that time and money should suffice to correct current deficiencies. The APSE and ARTE are, on the other hand, significantly newer issues within most software development and maintenance efforts. Currently, APSE and ARTE are highly dependent on differing implementer concepts, strategies, and market objectives. Complex and sophisticated mission-critical computing systems require the use of a complete Ada-based capability, not just the programming language itself; yet the range of APSE and ARTE features which must actually be utilized can vary significantly from one system to another. As a consequence, the need to understand, objectively evaluate, and select differing APSE and ARTE capabilities and features is critical to the effective use of Ada and the life-cycle efficiencies it is intended to promote. It is the selection, collection, and understanding of APSE and ARTE which provide the deeper challenges of using Ada for real-life mission-critical computing systems. Some of the current issues which must be clarified, often on a case-by-case basis, in order to successfully realize the full capabilities of Ada are discussed.

  14. Functional and molecular characterization of the transcriptional regulatory region of Tcp-10bt, a testes-expressed gene from the t complex responder locus.

    PubMed

    Ewulonu, U K; Buratynski, T J; Schimenti, J C

    1993-01-01

    Mouse t haplotypes contain several mutant alleles that disrupt spermatogenesis. Their phenotypes include sterility, reduced fertility and transmission ratio distortion (TRD). The substantial genetic analyses of these mutant alleles, coupled with intensive physical characterization of the t complex, provides a fertile ground for identifying and understanding genes essential to male gametogenesis. The t complex responder (Tcr) locus plays a central role in this process, interacting with other t haplotype-encoded genes to mediate TRD. A candidate responder gene, Tcp-10bt, has been cloned and subjected to molecular characterization. Here, we define the transcriptional regulatory regions of this gene in transgenic mice. A 1.6 kb (but not 0.6 kb) DNA fragment upstream of the transcription start site contains all the regulatory signals for appropriate temporal and germ cell-specific expression of this gene. Two smaller fragments within this region bound specifically to nuclear factor(s) from germ cell protein extracts in gel shift assays. This work is a step towards understanding the mechanism of Tcp-10bt regulated expression and may ultimately help reveal a common regulatory pathway shared by other similarly expressed spermatogenic genes. PMID:8223262

  15. Ada Structure Design Language (ASDL)

    NASA Technical Reports Server (NTRS)

    Chedrawi, Lutfi

    1986-01-01

    An artist acquires all the necessary tools before painting a scene. In the same analogy, a software engineer needs the necessary tools to provide their design with the proper means for implementation. Ada provide these tools. Yet, as an artist's painting needs a brochure to accompany it for further explanation of the scene, an Ada design also needs a document along with it to show the design in its detailed structure and hierarchical order. Ada could be self-explanatory in small programs not exceeding fifty lines of code in length. But, in a large environment, ranging from thousands of lines and above, Ada programs need to be well documented to be preserved and maintained. The language used to specify an Ada document is called Ada Structure Design Language (ASDL). This language sets some rules to help derive a well formatted Ada detailed design document. The rules are defined to meet the needs of a project manager, a maintenance team, a programmer and a systems designer. The design document templates, the document extractor, and the rules set forth by the ASDL are explained in detail.

  16. Phylogenetic divergence of CD47 interactions with human signal regulatory protein alpha reveals locus of species specificity. Implications for the binding site.

    PubMed

    Subramanian, Shyamsundar; Boder, Eric T; Discher, Dennis E

    2007-01-19

    Cell-cell interactions between ubiquitously expressed integrin-associated protein (CD47) and its counterreceptor signal regulatory protein (SIRPalpha) on phagocytes regulate a wide range of adhesive signaling processes, including the inhibition of phagocytosis as documented in mice. We show that CD47-SIRPalpha binding interactions are different between mice and humans, and we exploit phylogenetic divergence to identify the species-specific binding locus on the immunoglobulin domain of human CD47. All of the studies are conducted in the physiological context of membrane protein display on Chinese hamster ovary (CHO) cells. Novel quantitative flow cytometry analyses with CD47-green fluorescent protein and soluble human SIRPalpha as a probe show that neither human CD47 nor SIRPalpha requires glycosylation for interaction. Human CD47-expressing CHO cells spread rapidly on SIRPalpha-coated glass surfaces, correlating well with the spreading of primary human T cells. In contrast, CHO cells expressing mouse CD47 spread minimally and show equally weak binding to soluble human SIRPalpha. Further phylogenetic analyses and multisite substitutions of the CD47 Ig domain show that human to cow mutation of a cluster of seven residues on adjacent strands near the middle of the domain decreases the association constant for human SIRPalpha to about one-third that of human CD47. Direct tests of cell-cell adhesion between human monocytes and CD47-displaying CHO cells affirm the species specificity as well as the importance of the newly identified binding locus in cell-cell interactions.

  17. Update of GRASP/Ada reverse engineering tools for Ada

    NASA Technical Reports Server (NTRS)

    Cross, James H., II

    1993-01-01

    The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional pretty printed Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype CSD generator (Version 1) was designed and implemented using FLEX and BISON running under VMS on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented using the HP widget toolkit and the X Windows System. In Phase 3, the user interface was extensively reworked using the Athena widget toolkit and X Windows. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. Following Phase 3,e two update phases were completed. Update'92 focused on the initial analysis of evaluation data collected from software engineering students at Auburn University and the addition of significant enhancements to the user interface. Update'93 (the current update) focused on the statistical analysis of the data collected in the previous update and preparation of Version 3.4 of the prototype for limited distribution to facilitate further evaluation. The current prototype provides the capability for the user to generate CSD's from Ada PDL or source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical

  18. Crosstalk between bone marrow-derived mesenchymal stem cells and regulatory T cells through a glucocorticoid-induced leucine zipper/developmental endothelial locus-1-dependent mechanism

    PubMed Central

    Yang, Nianlan; Baban, Babak; Isales, Carlos M.; Shi, Xing-Ming

    2015-01-01

    Bone marrow is a reservoir for regulatory T (Treg) cells, but how Treg cells are regulated in that environment remains poorly understood. We show that expression of glucocorticoid (GC)-induced leucine zipper (GILZ) in bone marrow mesenchymal lineage cells or bone marrow-derived mesenchymal stem cells (BMSCs) increases the production of Treg cells via a mechanism involving the up-regulation of developmental endothelial locus-1 (Del-1), an endogenous leukocyte-endothelial adhesion inhibitor. We found that the expression of Del-1 is increased ∼4-fold in the bone tissues of GILZ transgenic (Tg) mice, and this increase is coupled with a significant increase in the production of IL-10 (2.80 vs. 0.83) and decrease in the production of IL-6 (0.80 vs. 2.33) and IL-12 (0.25 vs. 1.67). We also show that GILZ-expressing BMSCs present antigen in a way that favors Treg cells. These results indicate that GILZ plays a critical role mediating the crosstalk between BMSCs and Treg in the bone marrow microenvironment. These data, together with our previous findings that overexpression of GILZ in BMSCs antagonizes TNF-α-elicited inflammatory responses, suggest that GILZ plays important roles in bone-immune cell communication and BMSC immune suppressive functions.—Yang, N., Baban, B., Isales, C. M., Shi, X.-M. Crosstalk between bone marrow-derived mesenchymal stem cells and regulatory T cells through a glucocorticoid-induced leucine zipper/developmental endothelial locus-1-dependent mechanism. PMID:26038125

  19. Ada Linear-Algebra Program

    NASA Technical Reports Server (NTRS)

    Klumpp, A. R.; Lawson, C. L.

    1988-01-01

    Routines provided for common scalar, vector, matrix, and quaternion operations. Computer program extends Ada programming language to include linear-algebra capabilities similar to HAS/S programming language. Designed for such avionics applications as software for Space Station.

  20. GRASP/Ada 95: Reverse Engineering Tools for Ada

    NASA Technical Reports Server (NTRS)

    Cross, James H., II

    1996-01-01

    The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped an algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD), and a new visualization for a fine-grained complexity metric called the Complexity Profile Graph (CPG). By synchronizing the CSD and the CPG, the CSD view of control structure, nesting, and source code is directly linked to the corresponding visualization of statement level complexity in the CPG. GRASP has been integrated with GNAT, the GNU Ada 95 Translator to provide a comprehensive graphical user interface and development environment for Ada 95. The user may view, edit, print, and compile source code as a CSD with no discernible addition to storage or computational overhead. The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada 95 source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. The current update has focused on the design and implementation of a new Motif compliant user interface, and a new CSD generator consisting of a tagger and renderer. The Complexity Profile Graph (CPG) is based on a set of functions that describes the context, content, and the scaling for complexity on a statement by statement basis. When combined graphicafly, the result is a composite profile of complexity for the program unit. Ongoing research includes the development and refinement of the associated functions, and the development of the CPG generator prototype. The current Version 5.0 prototype provides the capability for the user to generate CSDs and CPGs from Ada 95 source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for

  1. An Ada programming support environment

    NASA Technical Reports Server (NTRS)

    Tyrrill, AL; Chan, A. David

    1986-01-01

    The toolset of an Ada Programming Support Environment (APSE) being developed at North American Aircraft Operations (NAAO) of Rockwell International, is described. The APSE is resident on three different hosts and must support developments for the hosts and for embedded targets. Tools and developed software must be freely portable between the hosts. The toolset includes the usual editors, compilers, linkers, debuggers, configuration magnagers, and documentation tools. Generally, these are being supplied by the host computer vendors. Other tools, for example, pretty printer, cross referencer, compilation order tool, and management tools were obtained from public-domain sources, are implemented in Ada and are being ported to the hosts. Several tools being implemented in-house are of interest, these include an Ada Design Language processor based on compilable Ada. A Standalone Test Environment Generator facilitates test tool construction and partially automates unit level testing. A Code Auditor/Static Analyzer permits the Ada programs to be evaluated against measures of quality. An Ada Comment Box Generator partially automates generation of header comment boxes.

  2. Germline deletion of Igh 3′ regulatory region elements hs5-7 affects B cell specific regulation, rearrangement and insulation of the Igh locus1

    PubMed Central

    Volpi, Sabrina A.; Verma-Gaur, Jiyoti; Hassan, Rabih; Ju, Zhongliang; Roa, Sergio; Chatterjee, Sanjukta; Werling, Uwe; Hou, Harry; Will, Britta; Steidl, Ulrich; Scharff, Matthew; Edelman, Winfried; Feeney, Ann J.; Birshtein, Barbara K.

    2012-01-01

    Regulatory elements located within a ~28 kb region 3′ of the Igh gene cluster (3′ regulatory region, 3′ RR) are required for class switch recombination and for high levels of IgH expression in plasma cells. We previously defined novel DNase I hypersensitive (hs) sites, i.e. hs5-7, immediately downstream of this region. Hs5-7 contains a high density of binding sites for CTCF, a zinc finger protein associated with mammalian insulator activity and is an anchor for interactions with CTCF sites flanking the DH region. To test the function of hs5-7, we have generated mice with an 8 kb deletion encompassing all three hs elements. B cells from hs5-7 KO mice showed a modest increase in expression of the nearest downstream gene. In addition, Igh alleles in hs5-7 KO mice were in a less contracted configuration compared to WT Igh alleles and showed a two-fold increase in the usage of proximal VH7183 gene families. Hs5-7 KO mice were essentially indistinguishable from wild type mice in B cell development, allelic regulation, class switch recombination, and chromosomal looping. We conclude that hs5-7--a high-density CTCF binding region at the 3′ end of the Igh locus--impacts usage of VH regions as far as 500 kb away. PMID:22345664

  3. Paranoia.Ada: Sample output reports

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Paranoia.Ada is a program to diagnose floating point arithmetic in the context of the Ada programming language. The program evaluates the quality of a floating point arithmetic implementation with respect to the proposed IEEE Standards P754 and P854. Paranoia.Ada is derived from the original BASIC programming language version of Paranoia. The Paranoia.Ada replicates in Ada the test algorithms originally implemented in BASIC and adheres to the evaluation criteria established by W. M. Kahan. Paranoia.Ada incorporates a major structural redesign and employs applicable Ada architectural and stylistic features.

  4. ART-Ada design project, phase 2

    NASA Technical Reports Server (NTRS)

    Lee, S. Daniel; Allen, Bradley P.

    1990-01-01

    Interest in deploying expert systems in Ada has increased. An Ada based expert system tool is described called ART-Ada, which was built to support research into the language and methodological issues of expert systems in Ada. ART-Ada allows applications of an existing expert system tool called ART-IM (Automated Reasoning Tool for Information Management) to be deployed in various Ada environments. ART-IM, a C-based expert system tool, is used to generate Ada source code which is compiled and linked with an Ada based inference engine to produce an Ada executable image. ART-Ada is being used to implement several expert systems for NASA's Space Station Freedom Program and the U.S. Air Force.

  5. Ada/POSIX binding: A focused Ada investigation

    NASA Technical Reports Server (NTRS)

    Legrand, Sue

    1988-01-01

    NASA is seeking an operating system interface definition (OSID) for the Space Station Program (SSP) in order to take advantage of the commercial off-the-shelf (COTS) products available today and the many that are expected in the future. NASA would also like to avoid the reliance on any one source for operating systems, information system, communication system, or instruction set architecture. The use of the Portable Operating System Interface for Computer Environments (POSIX) is examined as a possible solution to this problem. Since Ada is already the language of choice for SSP, the question of an Ada/POSIX binding is addressed. The intent of the binding is to provide access to the POSIX standard operation system (OS) interface and environment, by which application portability of Ada applications will be supported at the source code level. A guiding principle of Ada/POSIX binding development is a clear conformance of the Ada interface with the functional definition of POSIX. The interface is intended to be used by both application developers and system implementors. The objective is to provide a standard that allows a strictly conforming application source program that can be compiled to execute on any conforming implementation. Special emphasis is placed on first providing those functions and facilities that are needed in a wide variety of commercial applications

  6. NF-κB and BRG1 bind a distal regulatory element in the IL-3/GM-CSF locus.

    PubMed

    Wurster, Andrea L; Precht, Patricia; Pazin, Michael J

    2011-09-01

    We investigated gene regulation at the IL-3/GM-CSF gene cluster. We found BRG1, a SWI/SNF remodeling ATPase, bound a distal element, CNSa. BRG1 binding was strongest in differentiated, stimulated T helper cells, paralleling IL-3 and GM-CSF expression. Depletion of BRG1 reduced IL-3 and GM-CSF transcription. BAF-specific SWI/SNF subunits bound to this locus and regulated IL-3 expression. CNSa was in closed chromatin in fibroblasts, open chromatin in differentiated T helper cells, and moderately open chromatin in naïve (undifferentiated) T helper cells; BRG1 was required for the most open state. CNSa increased transcription of a reporter in an episomal expression system, in a BRG1-dependent manner. The NF-κB subunit RelA/p65 bound CNSa in activated T helper cells. Inhibition of NF-κB blocked BRG1 binding to CNSa, chromatin opening at CNSa, and activation of IL-3 and GM-CSF. Together, these findings suggest CNSa is a distal enhancer that binds BRG1 and NF-κB.

  7. NF-κB and BRG1 bind a distal regulatory element in the IL-3/GM-CSF locus

    PubMed Central

    Wurster, Andrea L.; Precht, Patricia; Pazin, Michael J.

    2011-01-01

    We investigated gene regulation at the IL-3/GM-CSF gene cluster. We found BRG1, a SWI/SNF remodeling ATPase, bound a distal element, CNSa. BRG1 binding was strongest in differentiated, stimulated T helper cells, paralleling IL-3 and GM-CSF expression. Depletion of BRG1 reduced IL-3 and GM-CSF transcription. BAF-specific SWI/SNF subunits bound to this locus and regulated IL-3 expression. CNSa was in closed chromatin in fibroblasts, open chromatin in differentiated T helper cells, and moderately open chromatin in naïve (undifferentiated) T helper cells; BRG1 was required for the most open state. CNSa increased transcription of a reporter in an episomal expression system, in a BRG1-dependent manner. The NF-κB subunit RelA/p65 bound CNSa in activated T helper cells. Inhibition of NF-κB blocked BRG1 binding to CNSa, chromatin opening at CNSa, and activation of IL-3 and GM-CSF. Together, these findings suggest CNSa is a distal enhancer that binds BRG1 and NF-κB. PMID:21831442

  8. Population genetic and phylogenetic evidence for positive selection on regulatory mutations at the factor VII locus in humans.

    PubMed Central

    Hahn, Matthew W; Rockman, Matthew V; Soranzo, Nicole; Goldstein, David B; Wray, Gregory A

    2004-01-01

    The abundance of cis-regulatory polymorphisms in humans suggests that many may have been important in human evolution, but evidence for their role is relatively rare. Four common polymorphisms in the 5' promoter region of factor VII (F7), a coagulation factor, have been shown to affect its transcription and protein abundance both in vitro and in vivo. Three of these polymorphisms have low-frequency alleles that decrease expression of F7 and may provide protection against myocardial infarction (heart attacks). The fourth polymorphism has a minor allele that increases the level of transcription. To look for evidence of natural selection on the cis-regulatory variants flanking F7, we genotyped three of the polymorphisms in six Old World populations for which we also have data from a group of putatively neutral SNPs. Our population genetic analysis shows evidence for selection within humans; surprisingly, the strongest evidence is due to a large increase in frequency of the high-expression variant in Singaporean Chinese. Further characterization of a Japanese population shows that at least part of the increase in frequency of the high-expression allele is found in other East Asian populations. In addition, to examine interspecific patterns of selection we sequenced the homologous 5' noncoding region in chimpanzees, bonobos, a gorilla, an orangutan, and a baboon. Analysis of these data reveals an excess of fixed differences within transcription factor binding sites along the human lineage. Our results thus further support the hypothesis that regulatory mutations have been important in human evolution. PMID:15238535

  9. Quantitative Trait Locus Based Virulence Determinant Mapping of the HSV-1 Genome in Murine Ocular Infection: Genes Involved in Viral Regulatory and Innate Immune Networks Contribute to Virulence

    PubMed Central

    Larsen, Inna; Craven, Mark; Brandt, Curtis R.

    2016-01-01

    Herpes simplex virus type 1 causes mucocutaneous lesions, and is the leading cause of infectious blindness in the United States. Animal studies have shown that the severity of HSV-1 ocular disease is influenced by three main factors; innate immunity, host immune response and viral strain. We previously showed that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) resulted in recombinants that exhibit a range of disease phenotypes from severe to avirulent, suggesting epistatic interactions were involved. The goal of this study was to develop a quantitative trait locus (QTL) analysis of HSV-1 ocular virulence determinants and to identify virulence associated SNPs. Blepharitis and stromal keratitis quantitative scores were characterized for 40 OD4:CJ994 recombinants. Viral titers in the eye were also measured. Virulence quantitative trait locus mapping (vQTLmap) was performed using the Lasso, Random Forest, and Ridge regression methods to identify significant phenotypically meaningful regions for each ocular disease parameter. The most predictive Ridge regression model identified several phenotypically meaningful SNPs for blepharitis and stromal keratitis. Notably, phenotypically meaningful nonsynonymous variations were detected in the UL24, UL29 (ICP8), UL41 (VHS), UL53 (gK), UL54 (ICP27), UL56, ICP4, US1 (ICP22), US3 and gG genes. Network analysis revealed that many of these variations were in HSV-1 regulatory networks and viral genes that affect innate immunity. Several genes previously implicated in virulence were identified, validating this approach, while other genes were novel. Several novel polymorphisms were also identified in these genes. This approach provides a framework that will be useful for identifying virulence genes in other pathogenic viruses, as well as epistatic effects that affect HSV-1 ocular virulence. PMID:26962864

  10. Quantitative Trait Locus Based Virulence Determinant Mapping of the HSV-1 Genome in Murine Ocular Infection: Genes Involved in Viral Regulatory and Innate Immune Networks Contribute to Virulence.

    PubMed

    Kolb, Aaron W; Lee, Kyubin; Larsen, Inna; Craven, Mark; Brandt, Curtis R

    2016-03-01

    Herpes simplex virus type 1 causes mucocutaneous lesions, and is the leading cause of infectious blindness in the United States. Animal studies have shown that the severity of HSV-1 ocular disease is influenced by three main factors; innate immunity, host immune response and viral strain. We previously showed that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) resulted in recombinants that exhibit a range of disease phenotypes from severe to avirulent, suggesting epistatic interactions were involved. The goal of this study was to develop a quantitative trait locus (QTL) analysis of HSV-1 ocular virulence determinants and to identify virulence associated SNPs. Blepharitis and stromal keratitis quantitative scores were characterized for 40 OD4:CJ994 recombinants. Viral titers in the eye were also measured. Virulence quantitative trait locus mapping (vQTLmap) was performed using the Lasso, Random Forest, and Ridge regression methods to identify significant phenotypically meaningful regions for each ocular disease parameter. The most predictive Ridge regression model identified several phenotypically meaningful SNPs for blepharitis and stromal keratitis. Notably, phenotypically meaningful nonsynonymous variations were detected in the UL24, UL29 (ICP8), UL41 (VHS), UL53 (gK), UL54 (ICP27), UL56, ICP4, US1 (ICP22), US3 and gG genes. Network analysis revealed that many of these variations were in HSV-1 regulatory networks and viral genes that affect innate immunity. Several genes previously implicated in virulence were identified, validating this approach, while other genes were novel. Several novel polymorphisms were also identified in these genes. This approach provides a framework that will be useful for identifying virulence genes in other pathogenic viruses, as well as epistatic effects that affect HSV-1 ocular virulence. PMID:26962864

  11. A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus

    PubMed Central

    Beccari, Leonardo; Yakushiji-Kaminatsui, Nayuta; Woltering, Joost M.; Necsulea, Anamaria; Lonfat, Nicolas; Rodríguez-Carballo, Eddie; Mascrez, Benedicte; Yamamoto, Shiori; Kuroiwa, Atsushi

    2016-01-01

    During vertebrate limb development, Hoxd genes are regulated following a bimodal strategy involving two topologically associating domains (TADs) located on either side of the gene cluster. These regulatory landscapes alternatively control different subsets of Hoxd targets, first into the arm and subsequently into the digits. We studied the transition between these two global regulations, a switch that correlates with the positioning of the wrist, which articulates these two main limb segments. We show that the HOX13 proteins themselves help switch off the telomeric TAD, likely through a global repressive mechanism. At the same time, they directly interact with distal enhancers to sustain the activity of the centromeric TAD, thus explaining both the sequential and exclusive operating processes of these two regulatory domains. We propose a model in which the activation of Hox13 gene expression in distal limb cells both interrupts the proximal Hox gene regulation and re-enforces the distal regulation. In the absence of HOX13 proteins, a proximal limb structure grows without any sign of wrist articulation, likely related to an ancestral fish-like condition. PMID:27198226

  12. A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus.

    PubMed

    Beccari, Leonardo; Yakushiji-Kaminatsui, Nayuta; Woltering, Joost M; Necsulea, Anamaria; Lonfat, Nicolas; Rodríguez-Carballo, Eddie; Mascrez, Benedicte; Yamamoto, Shiori; Kuroiwa, Atsushi; Duboule, Denis

    2016-05-15

    During vertebrate limb development, Hoxd genes are regulated following a bimodal strategy involving two topologically associating domains (TADs) located on either side of the gene cluster. These regulatory landscapes alternatively control different subsets of Hoxd targets, first into the arm and subsequently into the digits. We studied the transition between these two global regulations, a switch that correlates with the positioning of the wrist, which articulates these two main limb segments. We show that the HOX13 proteins themselves help switch off the telomeric TAD, likely through a global repressive mechanism. At the same time, they directly interact with distal enhancers to sustain the activity of the centromeric TAD, thus explaining both the sequential and exclusive operating processes of these two regulatory domains. We propose a model in which the activation of Hox13 gene expression in distal limb cells both interrupts the proximal Hox gene regulation and re-enforces the distal regulation. In the absence of HOX13 proteins, a proximal limb structure grows without any sign of wrist articulation, likely related to an ancestral fish-like condition. PMID:27198226

  13. The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus.

    PubMed

    Sauter, Kristin A; Bouhlel, M Amine; O'Neal, Julie; Sester, David P; Tagoh, Hiromi; Ingram, Richard M; Pridans, Clare; Bonifer, Constanze; Hume, David A

    2013-01-01

    The gene encoding the receptor for macrophage colony-stimulating factor (CSF-1R) is expressed exclusively in cells of the myeloid lineages as well as trophoblasts. A conserved element in the second intron, Fms-Intronic Regulatory Element (FIRE), is essential for macrophage-specific transcription of the gene. However, the molecular details of how FIRE activity is regulated and how it impacts the Csf1r promoter have not been characterised. Here we show that agents that down-modulate Csf1r mRNA transcription regulated promoter activity altered the occupancy of key FIRE cis-acting elements including RUNX1, AP1, and Sp1 binding sites. We demonstrate that FIRE acts as an anti-sense promoter in macrophages and reversal of FIRE orientation within its native context greatly reduced enhancer activity in macrophages. Mutation of transcription initiation sites within FIRE also reduced transcription. These results demonstrate that FIRE is an orientation-specific transcribed enhancer element.

  14. AdaNET research plan

    NASA Technical Reports Server (NTRS)

    Mcbride, John G.

    1990-01-01

    The mission of the AdaNET research effort is to determine how to increase the availability of reusable Ada components and associated software engineering technology to both private and Federal sectors. The effort is structured to define the requirements for transfer of Federally developed software technology, study feasible approaches to meeting the requirements, and to gain experience in applying various technologies and practices. The overall approach to the development of the AdaNET System Specification is presented. A work breakdown structure is presented with each research activity described in detail. The deliverables for each work area are summarized. The overall organization and responsibilities for each research area are described. The schedule and necessary resources are presented for each research activity. The estimated cost is summarized for each activity. The project plan is fully described in the Super Project Expert data file contained on the floppy disk attached to the back cover of this plan.

  15. Multiprocessor performance modeling with ADAS

    NASA Technical Reports Server (NTRS)

    Hayes, Paul J.; Andrews, Asa M.

    1989-01-01

    A graph managing strategy referred to as the Algorithm to Architecture Mapping Model (ATAMM) appears useful for the time-optimized execution of application algorithm graphs in embedded multiprocessors and for the performance prediction of graph designs. This paper reports the modeling of ATAMM in the Architecture Design and Assessment System (ADAS) to make an independent verification of ATAMM's performance prediction capability and to provide a user framework for the evaluation of arbitrary algorithm graphs. Following an overview of ATAMM and its major functional rules are descriptions of the ADAS model of ATAMM, methods to enter an arbitrary graph into the model, and techniques to analyze the simulation results. The performance of a 7-node graph example is evaluated using the ADAS model and verifies the ATAMM concept by substantiating previously published performance results.

  16. Ada style guide (version 1.1)

    NASA Technical Reports Server (NTRS)

    Seidewitz, Edwin V.; Agresti, William; Ferry, Daniel; Lavallee, David; Maresca, Paul; Nelson, Robert; Quimby, Kelvin; Rosenberg, Jacob; Roy, Daniel; Shell, Allyn

    1987-01-01

    Ada is a programming language of considerable expressive power. The Ada Language Reference Manual provides a thorough definition of the language. However, it does not offer sufficient guidance on the appropriate use of Ada's powerful features. For this reason, the Goddard Space Flight Center Ada User's Group has produced this style guide which addresses such program style issues. The guide covers three areas of Ada program style: the structural decomposition of a program; the coding and the use of specific Ada features; and the textural formatting of a program.

  17. Molecular architecture of the regulatory Locus sae of Staphylococcus aureus and its impact on expression of virulence factors.

    PubMed

    Steinhuber, Andrea; Goerke, Christiane; Bayer, Manfred G; Döring, Gerd; Wolz, Christiane

    2003-11-01

    We characterized the sae operon, a global regulator for virulence gene expression in Staphylococcus aureus. A Tn917 sae mutant was obtained by screening a Tn917 library of the agr mutant ISP479Mu for clones with altered hemolytic activity. Sequence analysis of the sae operon revealed two additional open reading frames (ORFs) (ORF3 and ORF4) upstream of the two-component regulatory genes saeR and saeS. Four overlapping sae-specific transcripts (T1 to T4) were detected by Northern blot analysis, and the transcriptional initiation points were mapped by primer extension analysis. The T1, T2, and T3 mRNAs are probably terminated at the same stem-loop sequence downstream of saeS. The T1 message (3.1 kb) initiates upstream of ORF4, T2 (2.4 kb) initiates upstream of ORF3, and T3 (2.0 kb) initiates in front of saeR. T4 (0.7 kb) represents a monocistronic mRNA encompassing ORF4 only. sae-specific transcripts were detectable in all of the 40 different clinical S. aureus isolates investigated. Transcript levels were at maximum during the post-exponential growth phase. The sae mutant showed a significantly reduced rate of invasion of human endothelial cells, consistent with diminished transcription and expression of fnbA. The expression of type 5 capsular polysaccharide is activated in the sae mutant of strain Newman, as shown by immunofluorescence and promoter-reporter fusion experiments. In summary, the sae operon constitutes a four-component regulator system which acts on virulence gene expression in S. aureus.

  18. Software reuse issues affecting AdaNET

    NASA Technical Reports Server (NTRS)

    Mcbride, John G.

    1989-01-01

    The AdaNet program is reviewing its long-term goals and strategies. A significant concern is whether current AdaNet plans adequately address the major strategic issues of software reuse technology. The major reuse issues of providing AdaNet services that should be addressed as part of future AdaNet development are identified and reviewed. Before significant development proceeds, a plan should be developed to resolve the aforementioned issues. This plan should also specify a detailed approach to develop AdaNet. A three phased strategy is recommended. The first phase would consist of requirements analysis and produce an AdaNet system requirements specification. It would consider the requirements of AdaNet in terms of mission needs, commercial realities, and administrative policies affecting development, and the experience of AdaNet and other projects promoting the transfer software engineering technology. Specifically, requirements analysis would be performed to better understand the requirements for AdaNet functions. The second phase would provide a detailed design of the system. The AdaNet should be designed with emphasis on the use of existing technology readily available to the AdaNet program. A number of reuse products are available upon which AdaNet could be based. This would significantly reduce the risk and cost of providing an AdaNet system. Once a design was developed, implementation would proceed in the third phase.

  19. Americans with Disabilities Act (ADA). Feature Issue.

    ERIC Educational Resources Information Center

    Lakin, Charlie, Ed.; And Others

    1993-01-01

    This feature issue focuses on the Americans with Disabilities Act (ADA), with articles discussing provisions of the ADA and its impact on people with developmental disabilities. Articles have the following titles and authors: "The ADA: What Does It Mean for People with Developmental Disabilities?" (Deborah L. McFadden and Edward P. Burke); "The…

  20. Software unit testing in Ada environment

    NASA Technical Reports Server (NTRS)

    Warnock, Glenn

    1986-01-01

    A validation procedure for the Ada binding of the Graphical Kernel System (GKS) is being developed. PRIOR Data Sciences is also producing a version of the GKS written in Ada. These major software engineering projects will provide an opportunity to demonstrate a sound approach for software testing in an Ada environment. The GKS/Ada validation capability will be a collection of test programs and data, and test management guidelines. These products will be used to assess the correctness, completeness, and efficiency of any GKS/Ada implementation. The GKS/Ada developers will be able to obtain the validation software for their own use. It is anticipated that this validation software will eventually be taken over by an independent standards body to provide objective assessments of GKS/Ada implementations, using an approach similar to the validation testing currently applied to Ada compilers. In the meantime, if requested, this validation software will be used to assess GKS/Ada products. The second project, implementation of GKS using the Ada language, is a conventional software engineering tasks. It represents a large body of Ada code and has some interesting testing problems associated with automatic testing of graphics routines. Here the normal test practices which include automated regression testing, independent quality assistance, test configuration management, and the application of software quality metrics will be employed. The software testing methods emphasize quality enhancement and automated procedures. Ada makes some aspects of testing easier, and introduces some concerns. These issues are addressed.

  1. Ada--Programming Language of the Future.

    ERIC Educational Resources Information Center

    Rudd, David

    1983-01-01

    Ada is a programing language developed for the Department of Defense, with a registered trademark. It was named for Ada Augusta, coworker of Charles Babbage and the world's first programer. The Department of Defense hopes to prevent variations and to establish Ada as a consistent, standardized language. (MNS)

  2. Structuring the formal definition of Ada

    NASA Technical Reports Server (NTRS)

    Hansen, Kurt W.

    1986-01-01

    The structure of the formal definition of Ada are described. At present, a difficult subset of Ada has been defined and the experience gained so far by this work is reported. Currently, the work continues towards the formal definition of the Ada language.

  3. Acetylation of Mammalian ADA3 Is Required for Its Functional Roles in Histone Acetylation and Cell Proliferation.

    PubMed

    Mohibi, Shakur; Srivastava, Shashank; Bele, Aditya; Mirza, Sameer; Band, Hamid; Band, Vimla

    2016-10-01

    Alteration/deficiency in activation 3 (ADA3) is an essential component of specific histone acetyltransferase (HAT) complexes. We have previously shown that ADA3 is required for establishing global histone acetylation patterns and for normal cell cycle progression (S. Mohibi et al., J Biol Chem 287:29442-29456, 2012, http://dx.doi.org/10.1074/jbc.M112.378901). Here, we report that these functional roles of ADA3 require its acetylation. We show that ADA3 acetylation, which is dynamically regulated in a cell cycle-dependent manner, reflects a balance of coordinated actions of its associated HATs, GCN5, PCAF, and p300, and a new partner that we define, the deacetylase SIRT1. We use mass spectrometry and site-directed mutagenesis to identify major sites of ADA3 acetylated by GCN5 and p300. Acetylation-defective mutants are capable of interacting with HATs and other components of HAT complexes but are deficient in their ability to restore ADA3-dependent global or locus-specific histone acetylation marks and cell proliferation in Ada3-deleted murine embryonic fibroblasts (MEFs). Given the key importance of ADA3-containing HAT complexes in the regulation of various biological processes, including the cell cycle, our study presents a novel mechanism to regulate the function of these complexes through dynamic ADA3 acetylation. PMID:27402865

  4. Ada technology support for NASA-GSFC

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Utilization of the Ada programming language and environments to perform directorate functions was reviewed. The Mission and Data Operations Directorate Network (MNET) conversion effort was chosen as the first task for evaluation and assistance. The MNET project required the rewriting of the existing Network Control Program (NCP) in the Ada programming language. The DEC Ada compiler running on the VAX under WMS was used for the initial development efforts. Stress tests on the newly delivered version of the DEC Ada compiler were performed. The new Alsys Ada compiler was purchased for the IBM PC AT. A prevalidated version of the compiler was obtained. The compiler was then validated.

  5. Transmitter data collection using Ada

    NASA Technical Reports Server (NTRS)

    Conroy, B. L.

    1988-01-01

    A data collection system installed on the 400 kilowatt X-band transmitter of the Goldstone Solar System Radar is described. The data collection system is built around the off-the-shelf IEEE 488 instrumentation, linked with fiber optics, controlled by an inexpensive computer, and uses software written in the Ada language. The speed and accuracy of the system is discussed, along with programming techniques used for both data collection and reduction.

  6. Ada and cyclic runtime scheduling

    NASA Technical Reports Server (NTRS)

    Hood, Philip E.

    1986-01-01

    An important issue that must be faced while introducing Ada into the real time world is efficient and prodictable runtime behavior. One of the most effective methods employed during the traditional design of a real time system is the cyclic executive. The role cyclic scheduling might play in an Ada application in terms of currently available implementations and in terms of implementations that might be developed especially to support real time system development is examined. The cyclic executive solves many of the problems faced by real time designers, resulting in a system for which it is relatively easy to achieve approporiate timing behavior. Unfortunately a cyclic executive carries with it a very high maintenance penalty over the lifetime of the software that is schedules. Additionally, these cyclic systems tend to be quite fragil when any aspect of the system changes. The findings are presented of an ongoing SofTech investigation into Ada methods for real time system development. The topics covered include a description of the costs involved in using cyclic schedulers, the sources of these costs, and measures for future systems to avoid these costs without giving up the runtime performance of a cyclic system.

  7. QUEST/Ada (Query Utility Environment for Software Testing) of Ada: The development of a program analysis environment for Ada

    NASA Technical Reports Server (NTRS)

    Brown, David B.

    1988-01-01

    A history of the Query Utility Environment for Software Testing (QUEST)/Ada is presented. A fairly comprehensive literature review which is targeted toward issues of Ada testing is given. The definition of the system structure and the high level interfaces are then presented. The design of the three major components is described. The QUEST/Ada IORL System Specifications to this point in time are included in the Appendix. A paper is also included in the appendix which gives statistical evidence of the validity of the test case generation approach which is being integrated into QUEST/Ada.

  8. COMPASS: An Ada based scheduler

    NASA Technical Reports Server (NTRS)

    Mcmahon, Mary Beth; Culbert, Chris

    1992-01-01

    COMPASS is a generic scheduling system developed by McDonnell Douglas and funded by the Software Technology Branch of NASA Johnson Space Center. The motivation behind COMPASS is to illustrate scheduling technology and provide a basis from which custom scheduling systems can be built. COMPASS was written in Ada to promote readability and to conform to DOD standards. COMPASS has some unique characteristics that distinguishes it from commercial products. This paper discusses these characteristics and uses them to illustrate some differences between scheduling tools.

  9. Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression.

    PubMed

    Jones, Bart G; Penkert, Rhiannon R; Xu, Beisi; Fan, Yiping; Neale, Geoff; Gearhart, Patricia J; Hurwitz, Julia L

    2016-09-01

    Females and males differ in antibody isotype expression patterns and in immune responses to foreign- and self-antigens. For example, systemic lupus erythematosus is a condition that associates with the production of isotype-skewed anti-self antibodies, and exhibits a 9:1 female:male disease ratio. To explain differences between B cell responses in males and females, we sought to identify direct interactions of the estrogen receptor (ER) with the immunoglobulin heavy chain locus. This effort was encouraged by our previous identification of estrogen response elements (ERE) in heavy chain switch (S) regions. We conducted a full-genome chromatin immunoprecipitation analysis (ChIP-seq) using DNA from LPS-activated B cells and an ERα-specific antibody. Results revealed ER binding to a wide region of DNA, spanning sequences from the JH cluster to Cδ, with peaks in Eμ and Sμ sites. Additional peaks of ERα binding were coincident with hs1,2 and hs4 sites in the 3' regulatory region (3'RR) of the heavy chain locus. This first demonstration of direct binding of ER to key regulatory elements in the immunoglobulin locus supports our hypothesis that estrogen and other nuclear hormone receptors and ligands may directly influence antibody expression and class switch recombination (CSR). Our hypothesis encourages the conduct of new experiments to evaluate the consequences of ER binding. A better understanding of ER:DNA interactions in the immunoglobulin heavy chain locus, and respective mechanisms, may ultimately translate to better control of antibody expression, better protection against pathogens, and prevention of pathologies caused by auto-immune disease. PMID:27494228

  10. Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression.

    PubMed

    Jones, Bart G; Penkert, Rhiannon R; Xu, Beisi; Fan, Yiping; Neale, Geoff; Gearhart, Patricia J; Hurwitz, Julia L

    2016-09-01

    Females and males differ in antibody isotype expression patterns and in immune responses to foreign- and self-antigens. For example, systemic lupus erythematosus is a condition that associates with the production of isotype-skewed anti-self antibodies, and exhibits a 9:1 female:male disease ratio. To explain differences between B cell responses in males and females, we sought to identify direct interactions of the estrogen receptor (ER) with the immunoglobulin heavy chain locus. This effort was encouraged by our previous identification of estrogen response elements (ERE) in heavy chain switch (S) regions. We conducted a full-genome chromatin immunoprecipitation analysis (ChIP-seq) using DNA from LPS-activated B cells and an ERα-specific antibody. Results revealed ER binding to a wide region of DNA, spanning sequences from the JH cluster to Cδ, with peaks in Eμ and Sμ sites. Additional peaks of ERα binding were coincident with hs1,2 and hs4 sites in the 3' regulatory region (3'RR) of the heavy chain locus. This first demonstration of direct binding of ER to key regulatory elements in the immunoglobulin locus supports our hypothesis that estrogen and other nuclear hormone receptors and ligands may directly influence antibody expression and class switch recombination (CSR). Our hypothesis encourages the conduct of new experiments to evaluate the consequences of ER binding. A better understanding of ER:DNA interactions in the immunoglobulin heavy chain locus, and respective mechanisms, may ultimately translate to better control of antibody expression, better protection against pathogens, and prevention of pathologies caused by auto-immune disease.

  11. C Language Integrated Production System, Ada Version

    NASA Technical Reports Server (NTRS)

    Culbert, Chris; Riley, Gary; Savely, Robert T.; Melebeck, Clovis J.; White, Wesley A.; Mcgregor, Terry L.; Ferguson, Melisa; Razavipour, Reza

    1992-01-01

    CLIPS/Ada provides capabilities of CLIPS v4.3 but uses Ada as source language for CLIPS executable code. Implements forward-chaining rule-based language. Program contains inference engine and language syntax providing framework for construction of expert-system program. Also includes features for debugging application program. Based on Rete algorithm which provides efficient method for performing repeated matching of patterns. Written in Ada.

  12. ART/Ada design project, phase 1

    NASA Technical Reports Server (NTRS)

    1989-01-01

    An Ada-Based Expert System Building Tool Design Research Project was conducted. The goal was to investigate various issues in the context of the design of an Ada-based expert system building tool. An attempt was made to achieve a comprehensive understanding of the potential for embedding expert systems in Ada systems for eventual application in future projects. The current status of the project is described by introducing an operational prototype, ART/Ada. How the project was conducted is explained. The performance of the prototype is analyzed and compared with other related works. Future research directions are suggested.

  13. Subunits of ADA-two-A-containing (ATAC) or Spt-Ada-Gcn5-acetyltrasferase (SAGA) Coactivator Complexes Enhance the Acetyltransferase Activity of GCN5.

    PubMed

    Riss, Anne; Scheer, Elisabeth; Joint, Mathilde; Trowitzsch, Simon; Berger, Imre; Tora, László

    2015-11-27

    Histone acetyl transferases (HATs) play a crucial role in eukaryotes by regulating chromatin architecture and locus specific transcription. GCN5 (KAT2A) is a member of the GNAT (Gcn5-related N-acetyltransferase) family of HATs. In metazoans this enzyme is found in two functionally distinct coactivator complexes, SAGA (Spt Ada Gcn5 acetyltransferase) and ATAC (Ada Two A-containing). These two multiprotein complexes comprise complex-specific and shared subunits, which are organized in functional modules. The HAT module of ATAC is composed of GCN5, ADA2a, ADA3, and SGF29, whereas in the SAGA HAT module ADA2b is present instead of ADA2a. To better understand how the activity of human (h) hGCN5 is regulated in the two related, but different, HAT complexes we carried out in vitro HAT assays. We compared the activity of hGCN5 alone with its activity when it was part of purified recombinant hATAC or hSAGA HAT modules or endogenous hATAC or hSAGA complexes using histone tail peptides and full-length histones as substrates. We demonstrated that the subunit environment of the HAT complexes into which GCN5 incorporates determines the enhancement of GCN5 activity. On histone peptides we show that all the tested GCN5-containing complexes acetylate mainly histone H3K14. Our results suggest a stronger influence of ADA2b as compared with ADA2a on the activity of GCN5. However, the lysine acetylation specificity of GCN5 on histone tails or full-length histones was not changed when incorporated in the HAT modules of ATAC or SAGA complexes. Our results thus demonstrate that the catalytic activity of GCN5 is stimulated by subunits of the ADA2a- or ADA2b-containing HAT modules and is further increased by incorporation of the distinct HAT modules in the ATAC or SAGA holo-complexes.

  14. Ada training evaluation and recommendations from the Gamma Ray Observatory Ada Development Team

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The Ada training experiences of the Gamma Ray Observatory Ada development team are related, and recommendations are made concerning future Ada training for software developers. Training methods are evaluated, deficiencies in the training program are noted, and a recommended approach, including course outline, time allocation, and reference materials, is offered.

  15. Proceedings of the 2nd NASA Ada User's Symposium

    NASA Technical Reports Server (NTRS)

    1989-01-01

    Several presentations, mostly in viewgraph form, on various topics relating to Ada applications are given. Topics covered include the use of Ada in NASA, Ada and the Space Station, the software support environment, Ada in the Software Engineering Laboratory, Ada at the Jet Propulsion Laboratory, the Flight Telerobotic Servicer, and lessons learned in prototyping the Space Station Remote Manipulator System control.

  16. Paranoia.Ada: A diagnostic program to evaluate Ada floating-point arithmetic

    NASA Technical Reports Server (NTRS)

    Hjermstad, Chris

    1986-01-01

    Many essential software functions in the mission critical computer resource application domain depend on floating point arithmetic. Numerically intensive functions associated with the Space Station project, such as emphemeris generation or the implementation of Kalman filters, are likely to employ the floating point facilities of Ada. Paranoia.Ada appears to be a valuabe program to insure that Ada environments and their underlying hardware exhibit the precision and correctness required to satisfy mission computational requirements. As a diagnostic tool, Paranoia.Ada reveals many essential characteristics of an Ada floating point implementation. Equipped with such knowledge, programmers need not tremble before the complex task of floating point computation.

  17. A small evaluation suite for Ada compilers

    NASA Technical Reports Server (NTRS)

    Wilke, Randy; Roy, Daniel M.

    1986-01-01

    After completing a small Ada pilot project (OCC simulator) for the Multi Satellite Operations Control Center (MSOCC) at Goddard last year, the use of Ada to develop OCCs was recommended. To help MSOCC transition toward Ada, a suite of about 100 evaluation programs was developed which can be used to assess Ada compilers. These programs compare the overall quality of the compilation system, compare the relative efficiencies of the compilers and the environments in which they work, and compare the size and execution speed of generated machine code. Another goal of the benchmark software was to provide MSOCC system developers with rough timing estimates for the purpose of predicting performance of future systems written in Ada.

  18. The development of a program analysis environment for Ada: Reverse engineering tools for Ada

    NASA Technical Reports Server (NTRS)

    Cross, James H., II

    1991-01-01

    The Graphical Representations of Algorithms, Structures, and Processes for Ada (GRASP/Ada) has successfully created and prototyped a new algorithm level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and thus improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under the Virtual Memory System (VMS) on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. In Phase 3 of the project, the prototype was prepared for limited distribution (GRASP/Ada Version 3.0) to facilitate evaluation. The user interface was extensively reworked. The current prototype provides the capability for the user to generate CSD from Ada source code in a reverse engineering mode with a level of flexibility suitable for practical application.

  19. Homologous Elements hs3a and hs3b in the 3′ Regulatory Region of the Murine Immunoglobulin Heavy Chain (Igh) Locus Are Both Dispensable for Class-switch Recombination*

    PubMed Central

    Yan, Yi; Pieretti, Joyce; Ju, Zhongliang; Wei, Shiniu; Christin, John R.; Bah, Fatmata; Birshtein, Barbara K.; Eckhardt, Laurel A.

    2011-01-01

    Immunoglobulin heavy chain (IgH) genes are formed, tested, and modified to yield diverse, specific, and high affinity antibody responses to antigen. The processes involved must be regulated, however, to avoid unintended damage to chromosomes. The 3′ regulatory region of the Igh locus plays a major role in regulating class-switch recombination (CSR), the process by which antibody effector functions are modified during an immune response. Loss of all known enhancer-like elements in this region dramatically impairs CSR, but individual element deletions have no effect on this process. In the present study, we explored the hypothesis that an underlying functional redundancy in the homologous elements hs3a and hs3b was masking the importance of either element to CSR. Several transgenic mouse lines were generated, each carrying a bacterial artificial chromosome transgene that mimicked Igh locus structure but in which hs3a was missing and hs3b was flanked by loxP sites. Matings to Cyclization Recombination Enzyme-expressing mice established “pairs” of lines that differed only in the presence or absence of hs3b. Remarkably, CSR remained robust in the absence of both hs3a and hs3b, suggesting that the remaining two elements of the 3′ regulatory region, hs1.2 and hs4, although individually dispensable for CSR, are, together, sufficient to support CSR. PMID:21673112

  20. Homologous elements hs3a and hs3b in the 3' regulatory region of the murine immunoglobulin heavy chain (Igh) locus are both dispensable for class-switch recombination.

    PubMed

    Yan, Yi; Pieretti, Joyce; Ju, Zhongliang; Wei, Shiniu; Christin, John R; Bah, Fatmata; Birshtein, Barbara K; Eckhardt, Laurel A

    2011-08-01

    Immunoglobulin heavy chain (IgH) genes are formed, tested, and modified to yield diverse, specific, and high affinity antibody responses to antigen. The processes involved must be regulated, however, to avoid unintended damage to chromosomes. The 3' regulatory region of the Igh locus plays a major role in regulating class-switch recombination (CSR), the process by which antibody effector functions are modified during an immune response. Loss of all known enhancer-like elements in this region dramatically impairs CSR, but individual element deletions have no effect on this process. In the present study, we explored the hypothesis that an underlying functional redundancy in the homologous elements hs3a and hs3b was masking the importance of either element to CSR. Several transgenic mouse lines were generated, each carrying a bacterial artificial chromosome transgene that mimicked Igh locus structure but in which hs3a was missing and hs3b was flanked by loxP sites. Matings to Cyclization Recombination Enzyme-expressing mice established "pairs" of lines that differed only in the presence or absence of hs3b. Remarkably, CSR remained robust in the absence of both hs3a and hs3b, suggesting that the remaining two elements of the 3' regulatory region, hs1.2 and hs4, although individually dispensable for CSR, are, together, sufficient to support CSR. PMID:21673112

  1. Homologous elements hs3a and hs3b in the 3' regulatory region of the murine immunoglobulin heavy chain (Igh) locus are both dispensable for class-switch recombination.

    PubMed

    Yan, Yi; Pieretti, Joyce; Ju, Zhongliang; Wei, Shiniu; Christin, John R; Bah, Fatmata; Birshtein, Barbara K; Eckhardt, Laurel A

    2011-08-01

    Immunoglobulin heavy chain (IgH) genes are formed, tested, and modified to yield diverse, specific, and high affinity antibody responses to antigen. The processes involved must be regulated, however, to avoid unintended damage to chromosomes. The 3' regulatory region of the Igh locus plays a major role in regulating class-switch recombination (CSR), the process by which antibody effector functions are modified during an immune response. Loss of all known enhancer-like elements in this region dramatically impairs CSR, but individual element deletions have no effect on this process. In the present study, we explored the hypothesis that an underlying functional redundancy in the homologous elements hs3a and hs3b was masking the importance of either element to CSR. Several transgenic mouse lines were generated, each carrying a bacterial artificial chromosome transgene that mimicked Igh locus structure but in which hs3a was missing and hs3b was flanked by loxP sites. Matings to Cyclization Recombination Enzyme-expressing mice established "pairs" of lines that differed only in the presence or absence of hs3b. Remarkably, CSR remained robust in the absence of both hs3a and hs3b, suggesting that the remaining two elements of the 3' regulatory region, hs1.2 and hs4, although individually dispensable for CSR, are, together, sufficient to support CSR.

  2. Development of an Ada programming support environment database SEAD (Software Engineering and Ada Database) administration manual

    NASA Technical Reports Server (NTRS)

    Liaw, Morris; Evesson, Donna

    1988-01-01

    Software Engineering and Ada Database (SEAD) was developed to provide an information resource to NASA and NASA contractors with respect to Ada-based resources and activities which are available or underway either in NASA or elsewhere in the worldwide Ada community. The sharing of such information will reduce duplication of effort while improving quality in the development of future software systems. SEAD data is organized into five major areas: information regarding education and training resources which are relevant to the life cycle of Ada-based software engineering projects such as those in the Space Station program; research publications relevant to NASA projects such as the Space Station Program and conferences relating to Ada technology; the latest progress reports on Ada projects completed or in progress both within NASA and throughout the free world; Ada compilers and other commercial products that support Ada software development; and reusable Ada components generated both within NASA and from elsewhere in the free world. This classified listing of reusable components shall include descriptions of tools, libraries, and other components of interest to NASA. Sources for the data include technical newletters and periodicals, conference proceedings, the Ada Information Clearinghouse, product vendors, and project sponsors and contractors.

  3. Experiences with Ada in an embedded system

    NASA Technical Reports Server (NTRS)

    Labaugh, Robert J.

    1988-01-01

    Recent experiences with using Ada in a real time environment are described. The application was the control system for an experimental robotic arm. The objectives of the effort were to experiment with developing embedded applications in Ada, evaluating the suitability of the language for the application, and determining the performance of the system. Additional objectives were to develop a control system based on the NASA/NBS Standard Reference Model for Telerobot Control System Architecture (NASREM) in Ada, and to experiment with the control laws and how to incorporate them into the NASREM architecture.

  4. Development of an Ada package library

    NASA Technical Reports Server (NTRS)

    Burton, Bruce; Broido, Michael

    1986-01-01

    A usable prototype Ada package library was developed and is currently being evaluated for use in large software development efforts. The library system is comprised of an Ada-oriented design language used to facilitate the collection of reuse information, a relational data base to store reuse information, a set of reusable Ada components and tools, and a set of guidelines governing the system's use. The prototyping exercise is discussed and the lessons learned from it have led to the definition of a comprehensive tool set to facilitate software reuse.

  5. A distributed programming environment for Ada

    NASA Technical Reports Server (NTRS)

    Brennan, Peter; Mcdonnell, Tom; Mcfarland, Gregory; Timmins, Lawrence J.; Litke, John D.

    1986-01-01

    Despite considerable commercial exploitation of fault tolerance systems, significant and difficult research problems remain in such areas as fault detection and correction. A research project is described which constructs a distributed computing test bed for loosely coupled computers. The project is constructing a tool kit to support research into distributed control algorithms, including a distributed Ada compiler, distributed debugger, test harnesses, and environment monitors. The Ada compiler is being written in Ada and will implement distributed computing at the subsystem level. The design goal is to provide a variety of control mechanics for distributed programming while retaining total transparency at the code level.

  6. Software engineering and Ada in design

    NASA Technical Reports Server (NTRS)

    Oneill, Don

    1986-01-01

    Modern software engineering promises significant reductions in software costs and improvements in software quality. The Ada language is the focus for these software methodology and tool improvements. The IBM FSD approach, including the software engineering practices that guide the systematic design and development of software products and the management of the software process are examined. The revised Ada design language adaptation is revealed. This four level design methodology is detailed including the purpose of each level, the management strategy that integrates the software design activity with the program milestones, and the technical strategy that maps the Ada constructs to each level of design. A complete description of each design level is provided along with specific design language recording guidelines for each level. Finally, some testimony is offered on education, tools, architecture, and metrics resulting from project use of the four level Ada design language adaptation.

  7. Extensions of ADA for SIMD parallel processing

    SciTech Connect

    Cline, C.; Siegel, H.J.

    1983-01-01

    In order to program SIMD (single instruction stream-multiple data stream) parallel machines used for tasks such as speech and image processing, a language with explicit parallel constructs is often desirable. The language ADA, developed by the Department of Defense, is used as a basis for such a language. Extensions of ADA which allow the user to specify such things as interprocessor communications and activation of processors are proposed. 25 references.

  8. Ada programming guidelines for deterministic storage management

    NASA Technical Reports Server (NTRS)

    Auty, David

    1988-01-01

    Previous reports have established that a program can be written in the Ada language such that the program's storage management requirements are determinable prior to its execution. Specific guidelines for ensuring such deterministic usage of Ada dynamic storage requirements are described. Because requirements may vary from one application to another, guidelines are presented in a most-restrictive to least-restrictive fashion to allow the reader to match appropriate restrictions to the particular application area under investigation.

  9. Parallel Ada benchmarks for the SVMS

    NASA Technical Reports Server (NTRS)

    Collard, Philippe E.

    1990-01-01

    The use of parallel processing paradigm to design and develop faster and more reliable computers appear to clearly mark the future of information processing. NASA started the development of such an architecture: the Spaceborne VHSIC Multi-processor System (SVMS). Ada will be one of the languages used to program the SVMS. One of the unique characteristics of Ada is that it supports parallel processing at the language level through the tasking constructs. It is important for the SVMS project team to assess how efficiently the SVMS architecture will be implemented, as well as how efficiently Ada environment will be ported to the SVMS. AUTOCLASS II, a Bayesian classifier written in Common Lisp, was selected as one of the benchmarks for SVMS configurations. The purpose of the R and D effort was to provide the SVMS project team with the version of AUTOCLASS II, written in Ada, that would make use of Ada tasking constructs as much as possible so as to constitute a suitable benchmark. Additionally, a set of programs was developed that would measure Ada tasking efficiency on parallel architectures as well as determine the critical parameters influencing tasking efficiency. All this was designed to provide the SVMS project team with a set of suitable tools in the development of the SVMS architecture.

  10. Toward the efficient implementation of expert systems in Ada

    NASA Technical Reports Server (NTRS)

    Lee, S. Daniel

    1990-01-01

    Here, the authors describe Ada language issues encountered during the development of ART-Ada, an expert system tool for Ada deployment. ART-Ada is being used to implement several expert system applications for the Space Station Freedom and the U.S. Air Force. Additional information is given on dynamic memory allocation.

  11. An Embedded Rule-Based Diagnostic Expert System in Ada

    NASA Technical Reports Server (NTRS)

    Jones, Robert E.; Liberman, Eugene M.

    1992-01-01

    Ada is becoming an increasingly popular programming language for large Government-funded software projects. Ada with it portability, transportability, and maintainability lends itself well to today's complex programming environment. In addition, expert systems have also assumed a growing role in providing human-like reasoning capability expertise for computer systems. The integration is discussed of expert system technology with Ada programming language, especially a rule-based expert system using an ART-Ada (Automated Reasoning Tool for Ada) system shell. NASA Lewis was chosen as a beta test site for ART-Ada. The test was conducted by implementing the existing Autonomous Power EXpert System (APEX), a Lisp-based power expert system, in ART-Ada. Three components, the rule-based expert systems, a graphics user interface, and communications software make up SMART-Ada (Systems fault Management with ART-Ada). The rules were written in the ART-Ada development environment and converted to Ada source code. The graphics interface was developed with the Transportable Application Environment (TAE) Plus, which generates Ada source code to control graphics images. SMART-Ada communicates with a remote host to obtain either simulated or real data. The Ada source code generated with ART-Ada, TAE Plus, and communications code was incorporated into an Ada expert system that reads the data from a power distribution test bed, applies the rule to determine a fault, if one exists, and graphically displays it on the screen. The main objective, to conduct a beta test on the ART-Ada rule-based expert system shell, was achieved. The system is operational. New Ada tools will assist in future successful projects. ART-Ada is one such tool and is a viable alternative to the straight Ada code when an application requires a rule-based or knowledge-based approach.

  12. Ada Run Time Support Environments and a common APSE Interface Set. [Ada Programming Support Environment

    NASA Technical Reports Server (NTRS)

    Mckay, C. W.; Bown, R. L.

    1985-01-01

    The paper discusses the importance of linking Ada Run Time Support Environments to the Common Ada Programming Support Environment (APSE) Interface Set (CAIS). A non-stop network operating systems scenario is presented to serve as a forum for identifying the important issues. The network operating system exemplifies the issues involved in the NASA Space Station data management system.

  13. An Ada inference engine for expert systems

    NASA Technical Reports Server (NTRS)

    Lavallee, David B.

    1986-01-01

    The purpose is to investigate the feasibility of using Ada for rule-based expert systems with real-time performance requirements. This includes exploring the Ada features which give improved performance to expert systems as well as optimizing the tradeoffs or workarounds that the use of Ada may require. A prototype inference engine was built using Ada, and rule firing rates in excess of 500 per second were demonstrated on a single MC68000 processor. The knowledge base uses a directed acyclic graph to represent production lines. The graph allows the use of AND, OR, and NOT logical operators. The inference engine uses a combination of both forward and backward chaining in order to reach goals as quickly as possible. Future efforts will include additional investigation of multiprocessing to improve performance and creating a user interface allowing rule input in an Ada-like syntax. Investigation of multitasking and alternate knowledge base representations will help to analyze some of the performance issues as they relate to larger problems.

  14. Transformation of ADA programs into silicon

    NASA Astrophysics Data System (ADS)

    Organick, E. I.; Lindstrom, G.; Smith, D. K.; Subrahmany; Carter, T.

    1982-03-01

    This report outlines the beginning steps taken in an integrated research effort toward the development of a methodology, and supporting systems, for transforming Ada programs, or program units, (directly) into corresponding VLSI systems. The time seems right to expect good results. The need is evident; special purpose systems should be realistic alternatives where simplicity, speed, reliability, and security ae dominant factors. Success in this research can lead to attractive options for embedded system applications. Ada programs can be regarded as ensembles of machines, one per program unit (module), which in turn may be mapped directly into corresponding VLSI structures on one or more chips with interconnecting (packet switched or other) communication nets. The research reported here is part of a five-year plan, the first year of which focuses on 'proving' the concepts through a realistic demonstration of methodology for a specific example Ada program (a silicon representation of part or all of the DoD Standard Internet Protocol, IP, initially expressed in Ada). Implicit in these objectives is the development of a set of hardware structuring paradigms (rewrite rules) whose application can ensure that transformation steps between levels of abstraction in the design process are well structured in order to preserve the integrity and, where possible, the clarity of the original Ada specification. Some paradigms, but of course not all, lead to highly efficient implementations.

  15. Proceedings of the First NASA Ada Users' Symposium

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Ada has the potential to be a part of the most significant change in software engineering technology within NASA in the last twenty years. Thus, it is particularly important that all NASA centers be aware of Ada experience and plans at other centers. Ada activity across NASA are covered, with presenters representing five of the nine major NASA centers and the Space Station Freedom Program Office. Projects discussed included - Space Station Freedom Program Office: the implications of Ada on training, reuse, management and the software support environment; Johnson Space Center (JSC): early experience with the use of Ada, software engineering and Ada training and the evaluation of Ada compilers; Marshall Space Flight Center (MSFC): university research with Ada and the application of Ada to Space Station Freedom, the Orbital Maneuvering Vehicle, the Aero-Assist Flight Experiment and the Secure Shuttle Data System; Lewis Research Center (LeRC): the evolution of Ada software to support the Space Station Power Management and Distribution System; Jet Propulsion Laboratory (JPL): the creation of a centralized Ada development laboratory and current applications of Ada including the Real-time Weather Processor for the FAA; and Goddard Space Flight Center (GSFC): experiences with Ada in the Flight Dynamics Division and the Extreme Ultraviolet Explorer (EUVE) project and the implications of GSFC experience for Ada use in NASA. Despite the diversity of the presentations, several common themes emerged from the program: Methodology - NASA experience in general indicates that the effective use of Ada requires modern software engineering methodologies; Training - It is the software engineering principles and methods that surround Ada, rather than Ada itself, which requires the major training effort; Reuse - Due to training and transition costs, the use of Ada may initially actually decrease productivity, as was clearly found at GSFC; and real-time work at LeRC, JPL and GSFC shows

  16. Applying Ada to Beech Starship avionics

    NASA Technical Reports Server (NTRS)

    Funk, David W.

    1986-01-01

    As Ada solidified in its development, it became evident that it offered advantages for avionics systems because of it support for modern software engineering principles and real time applications. An Ada programming support environment was developed for two major avionics subsystems in the Beech Starship. The two subsystems include electronic flight instrument displays and the flight management computer system. Both of these systems use multiple Intel 80186 microprocessors. The flight management computer provides flight planning, navigation displays, primary flight display of checklists and other pilot advisory information. Together these systems represent nearly 80,000 lines of Ada source code and to date approximately 30 man years of effort. The Beech Starship avionics systems are in flight testing.

  17. A database management capability for Ada

    NASA Technical Reports Server (NTRS)

    Chan, Arvola; Danberg, SY; Fox, Stephen; Landers, Terry; Nori, Anil; Smith, John M.

    1986-01-01

    The data requirements of mission critical defense systems have been increasing dramatically. Command and control, intelligence, logistics, and even weapons systems are being required to integrate, process, and share ever increasing volumes of information. To meet this need, systems are now being specified that incorporate data base management subsystems for handling storage and retrieval of information. It is expected that a large number of the next generation of mission critical systems will contain embedded data base management systems. Since the use of Ada has been mandated for most of these systems, it is important to address the issues of providing data base management capabilities that can be closely coupled with Ada. A comprehensive distributed data base management project has been investigated. The key deliverables of this project are three closely related prototype systems implemented in Ada. These three systems are discussed.

  18. Atomic Data and Modelling for Fusion: the ADAS Project

    NASA Astrophysics Data System (ADS)

    Summers, H. P.; O'Mullane, M. G.

    2011-05-01

    The paper is an update on the Atomic Data and Analysis Structure, ADAS, since ICAM-DATA06 and a forward look to its evolution in the next five years. ADAS is an international project supporting principally magnetic confinement fusion research. It has participant laboratories throughout the world, including ITER and all its partner countries. In parallel with ADAS, the ADAS-EU Project provides enhanced support for fusion research at Associated Laboratories and Universities in Europe and ITER. OPEN-ADAS, sponsored jointly by the ADAS Project and IAEA, is the mechanism for open access to principal ADAS atomic data classes and facilitating software for their use. EXTENDED-ADAS comprises a variety of special, integrated application software, beyond the purely atomic bounds of ADAS, tuned closely to specific diagnostic analyses and plasma models. The current scientific content and scope of these various ADAS and ADAS related activities are briefly reviewed. These span a number of themes including heavy element spectroscopy and models, charge exchange spectroscopy, beam emission spectroscopy and special features which provide a broad baseline of atomic modelling and support. Emphasis will be placed on `lifting the fundamental data baseline'—a principal ADAS task for the next few years. This will include discussion of ADAS and ADAS-EU coordinated and shared activities and some of the methods being exploited.

  19. Ada software productivity prototypes: A case study

    NASA Technical Reports Server (NTRS)

    Hihn, Jairus M.; Habib-Agahi, Hamid; Malhotra, Shan

    1988-01-01

    A case study of the impact of Ada on a Command and Control project completed at the Jet Propulsion Laboratory (JPL) is given. The data for this study was collected as part of a general survey of software costs and productivity at JPL and other NASA sites. The task analyzed is a successful example of the use of rapid prototyping as applied to command and control for the U.S. Air Force and provides the U.S. Air Force Military Airlift Command with the ability to track aircraft, air crews and payloads worldwide. The task consists of a replicated database at several globally distributed sites. The local databases at each site can be updated within seconds after changes are entered at any one site. The system must be able to handle up to 400,000 activities per day. There are currently seven sites, each with a local area network of computers and a variety of user displays; the local area networks are tied together into a single wide area network. Using data obtained for eight modules, totaling approximately 500,000 source lines of code, researchers analyze the differences in productivities between subtasks. Factors considered are percentage of Ada used in coding, years of programmer experience, and the use of Ada tools and modern programming practices. The principle findings are the following. Productivity is very sensitive to programmer experience. The use of Ada software tools and the use of modern programming practices are important; without such use Ada is just a large complex language which can cause productivity to decrease. The impact of Ada on development effort phases is consistent with earlier reports at the project level but not at the module level.

  20. Knowledge representation into Ada parallel processing

    NASA Technical Reports Server (NTRS)

    Masotto, Tom; Babikyan, Carol; Harper, Richard

    1990-01-01

    The Knowledge Representation into Ada Parallel Processing project is a joint NASA and Air Force funded project to demonstrate the execution of intelligent systems in Ada on the Charles Stark Draper Laboratory fault-tolerant parallel processor (FTPP). Two applications were demonstrated - a portion of the adaptive tactical navigator and a real time controller. Both systems are implemented as Activation Framework Objects on the Activation Framework intelligent scheduling mechanism developed by Worcester Polytechnic Institute. The implementations, results of performance analyses showing speedup due to parallelism and initial efficiency improvements are detailed and further areas for performance improvements are suggested.

  1. Ada in AI or AI in Ada. On developing a rationale for integration

    NASA Technical Reports Server (NTRS)

    Collard, Philippe E.; Goforth, Andre

    1988-01-01

    The use of Ada as an Artificial Intelligence (AI) language is gaining interest in the NASA Community, i.e., by parties who have a need to deploy Knowledge Based-Systems (KBS) compatible with the use of Ada as the software standard for the Space Station. A fair number of KBS and pseudo-KBS implementations in Ada exist today. Currently, no widely used guidelines exist to compare and evaluate these with one another. The lack of guidelines illustrates a fundamental problem inherent in trying to compare and evaluate implementations of any sort in languages that are procedural or imperative in style, such as Ada, with those in languages that are functional in style, such as Lisp. Discussed are the strengths and weakness of using Ada as an AI language and a preliminary analysis provided of factors needed for the development of criteria for the integration of these two families of languages and the environments in which they are implemented. The intent for developing such criteria is to have a logical rationale that may be used to guide the development of Ada tools and methodology to support KBS requirements, and to identify those AI technology components that may most readily and effectively be deployed in Ada.

  2. Gamma ray observatory dynamics simulator in Ada (GRODY)

    NASA Technical Reports Server (NTRS)

    1990-01-01

    This experiment involved the parallel development of dynamics simulators for the Gamma Ray Observatory in both FORTRAN and Ada for the purpose of evaluating the applicability of Ada to the NASA/Goddard Space Flight Center's flight dynamics environment. The experiment successfully demonstrated that Ada is a viable, valuable technology for use in this environment. In addition to building a simulator, the Ada team evaluated training approaches, developed an Ada methodology appropriate to the flight dynamics environment, and established a baseline for evaluating future Ada projects.

  3. AdaNET prototype library administration manual

    NASA Technical Reports Server (NTRS)

    Hanley, Lionel

    1989-01-01

    The functions of the AdaNET Prototype Library of Reusable Software Parts is described. Adopted from the Navy Research Laboratory's Reusability Guidebook (V.5.0), this is a working document, customized for use the the AdaNET Project. Within this document, the term part is used to denote the smallest unit controlled by a library and retrievable from it. A part may have several constituents, which may not be individually tracked. Presented are the types of parts which may be stored in the library and the relationships among those parts; a concept of trust indicators which provide measures of confidence that a user of a previously developed part may reasonably apply to a part for a new application; search and retrieval, configuration management, and communications among those who interact with the AdaNET Prototype Library; and the AdaNET Prototype, described from the perspective of its three major users: the part reuser and retriever, the part submitter, and the librarian and/or administrator.

  4. Alma Flor Ada: Writer, Translator, Storyteller.

    ERIC Educational Resources Information Center

    Brodie, Carolyn S.

    2003-01-01

    Discusses the work of children's author Alma Flor Ada, a Cuban native who has won awards honoring Latino writers and illustrators. Includes part of an interview that explores her background, describes activity ideas, and presents a bibliography of works written by her (several title published in both English and Spanish) as well as sources of…

  5. Using ADA Tasks to Simulate Operating Equipment

    NASA Technical Reports Server (NTRS)

    DeAcetis, Louis A.; Schmidt, Oron; Krishen, Kumar

    1990-01-01

    A method of simulating equipment using ADA tasks is discussed. Individual units of equipment are coded as concurrently running tasks that monitor and respond to input signals. This technique has been used in a simulation of the space-to-ground Communications and Tracking subsystem of Space Station Freedom.

  6. The Courts, the ADA, and the Academy

    ERIC Educational Resources Information Center

    Cope, David D.

    2005-01-01

    Litigation influences what goes on in the classroom. The Americans with Disabilities Act (ADA), other statutes, and legal precedent have defined reasonable restrictions on what qualifies as a handicap. Still, universities tend to go overboard--out of ignorance, and influenced by a culture that seems to champion every conceivable victim--in…

  7. Molecular Genetic Characterization of Six Recessive Viable Alleles of the Mouse Agouti Locus

    PubMed Central

    Hustad, C. M.; Perry, W. L.; Siracusa, L. D.; Rasberry, C.; Cobb, L.; Cattanach, B. M.; Kovatch, R.; Copeland, N. G.; Jenkins, N. A.

    1995-01-01

    The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein of 131 amino acids that acts as a molecular switch to instruct the melanocyte to make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations that up-regulate agouti expression are dominant to those causing decreased expression and result in yellow coat color. Other associated effects are obesity, diabetes, and increased susceptibility to tumors. To try to define important functional domains of the agouti protein, we have analyzed the molecular defects present in a series of recessive viable agouti mutations. In total, six alleles (a(mJ), a(u), a(da), a(16H), a(18H), a(e)) were examined at both the RNA and DNA level. Two of the alleles, a(16H) and a(e), result from mutations in the agouti coding region. Four alleles (a(mJ), a(u), a(18H), and a(da)) appear to represent regulatory mutations that down-regulate agouti expression. Interestingly, one of these mutations, a(18H), also appears to cause an immunological defect in the homozygous condition. This immunological defect is somewhat analogous to that observed in motheaten (me) mutant mice. Short and long-range restriction enzyme analyses of homozygous a(18H) DNA are consistent with the hypothesis that a(18H) results from a paracentric inversion where one end of the inversion maps in the 5' regulatory region of agouti and the other end in or near a gene that is required for normal immunological function. Cloning the breakpoints of this putative inversion should allow us to identify the gene that confers this interesting immunological disorder. PMID:7635290

  8. The computerization of programming: Ada (R) lessons learned

    NASA Technical Reports Server (NTRS)

    Struble, Dennis D.

    1986-01-01

    One of the largest systems yet written in Ada has been constructed. This system is the Intermetrics Ada compiler. Many lessons have been learned during the implementation of this Ada compiler. Some of these lessons, concentrating on those lessons relevant to large system implementations are described. The characteristics of the Ada compiler implementation project at Intermetrics are also described. Some specific experiences during the implementation are pointed out.

  9. Knowledge, programming, and programming cultures: LISP, C, and Ada

    NASA Technical Reports Server (NTRS)

    Rochowiak, Daniel

    1990-01-01

    The results of research 'Ada as an implementation language for knowledge based systems' are presented. The purpose of the research was to compare Ada to other programming languages. The report focuses on the programming languages Ada, C, and Lisp, the programming cultures that surround them, and the programming paradigms they support.

  10. 49 CFR 37.125 - ADA paratransit eligibility: Process.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false ADA paratransit eligibility: Process. 37.125... INDIVIDUALS WITH DISABILITIES (ADA) Paratransit as a Complement to Fixed Route Service § 37.125 ADA paratransit eligibility: Process. Each public entity required to provide complementary paratransit service...

  11. 49 CFR 37.123 - ADA paratransit eligibility: Standards.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false ADA paratransit eligibility: Standards. 37.123... INDIVIDUALS WITH DISABILITIES (ADA) Paratransit as a Complement to Fixed Route Service § 37.123 ADA paratransit eligibility: Standards. (a) Public entities required by § 37.121 of this subpart to...

  12. Comparing host and target environments for distributed Ada programs

    NASA Technical Reports Server (NTRS)

    Paulk, Mark C.

    1986-01-01

    The Ada programming language provides a means of specifying logical concurrency by using multitasking. Extending the Ada multitasking concurrency mechanism into a physically concurrent distributed environment which imposes its own requirements can lead to incompatibilities. These problems are discussed. Using distributed Ada for a target system may be appropriate, but when using the Ada language in a host environment, a multiprocessing model may be more suitable than retargeting an Ada compiler for the distributed environment. The tradeoffs between multitasking on distributed targets and multiprocessing on distributed hosts are discussed. Comparisons of the multitasking and multiprocessing models indicate different areas of application.

  13. Ada and software management in NASA: Assessment and recommendations

    NASA Technical Reports Server (NTRS)

    1989-01-01

    Recent NASA missions have required software systems that are larger, more complex, and more critical than NASA software systems of the past. The Ada programming language and the software methods and support environments associated with it are seen as potential breakthroughs in meeting NASA's software requirements. The findings of a study by the Ada and Software Management Assessment Working Group (ASMAWG) are presented. The study was chartered to perform three tasks: (1) assess the agency's ongoing and planned Ada activities; (2) assess the infrastructure (standards, policies, and internal organizations) supporting software management and the Ada activities; and (3) present an Ada implementation and use strategy appropriate for NASA over the next 5 years.

  14. SDI satellite autonomy using AI and Ada

    NASA Technical Reports Server (NTRS)

    Fiala, Harvey E.

    1990-01-01

    The use of Artificial Intelligence (AI) and the programming language Ada to help a satellite recover from selected failures that could lead to mission failure are described. An unmanned satellite will have a separate AI subsystem running in parallel with the normal satellite subsystems. A satellite monitoring subsystem (SMS), under the control of a blackboard system, will continuously monitor selected satellite subsystems to become alert to any actual or potential problems. In the case of loss of communications with the earth or the home base, the satellite will go into a survival mode to reestablish communications with the earth. The use of an AI subsystem in this manner would have avoided the tragic loss of the two recent Soviet probes that were sent to investigate the planet Mars and its moons. The blackboard system works in conjunction with an SMS and a reconfiguration control subsystem (RCS). It can be shown to be an effective way for one central control subsystem to monitor and coordinate the activities and loads of many interacting subsystems that may or may not contain redundant and/or fault-tolerant elements. The blackboard system will be coded in Ada using tools such as the ABLE development system and the Ada Production system.

  15. SEL Ada reuse analysis and representations

    NASA Technical Reports Server (NTRS)

    Kester, Rush

    1990-01-01

    Overall, it was revealed that the pattern of Ada reuse has evolved from initial reuse of utility components into reuse of generalized application architectures. Utility components were both domain-independent utilities, such as queues and stacks, and domain-specific utilities, such as those that implement spacecraft orbit and attitude mathematical functions and physics or astronomical models. The level of reuse was significantly increased with the development of a generalized telemetry simulator architecture. The use of Ada generics significantly increased the level of verbatum reuse, which is due to the ability, using Ada generics, to parameterize the aspects of design that are configurable during reuse. A key factor in implementing generalized architectures was the ability to use generic subprogram parameters to tailor parts of the algorithm embedded within the architecture. The use of object oriented design (in which objects model real world entities) significantly improved the modularity for reuse. Encapsulating into packages the data and operations associated with common real world entities creates natural building blocks for reuse.

  16. Ada education in a software life-cycle context

    NASA Technical Reports Server (NTRS)

    Clough, Anne J.

    1986-01-01

    Some of the experience gained from a comprehensive educational program undertaken at The Charles Stark Draper Lab. to introduce the Ada language and to transition modern software engineering technology into the development of Ada and non-Ada applications is described. Initially, a core group, which included manager, engineers and programmers, received training in Ada. An Ada Office was established to assume the major responsibility for training, evaluation, acquisition and benchmarking of tools, and consultation on Ada projects. As a first step in this process, and in-house educational program was undertaken to introduce Ada to the Laboratory. Later, a software engineering course was added to the educational program as the need to address issues spanning the entire software life cycle became evident. Educational efforts to date are summarized, with an emphasis on the educational approach adopted. Finally, lessons learned in administering this program are addressed.

  17. Ada (trademark) projects at NASA. Runtime environment issues and recommendations

    NASA Technical Reports Server (NTRS)

    Roy, Daniel M.; Wilke, Randall W.

    1988-01-01

    Ada practitioners should use this document to discuss and establish common short term requirements for Ada runtime environments. The major current Ada runtime environment issues are identified through the analysis of some of the Ada efforts at NASA and other research centers. The runtime environment characteristics of major compilers are compared while alternate runtime implementations are reviewed. Modifications and extensions to the Ada Language Reference Manual to address some of these runtime issues are proposed. Three classes of projects focusing on the most critical runtime features of Ada are recommended, including a range of immediately feasible full scale Ada development projects. Also, a list of runtime features and procurement issues is proposed for consideration by the vendors, contractors and the government.

  18. Object-oriented programming with mixins in Ada

    NASA Technical Reports Server (NTRS)

    Seidewitz, ED

    1992-01-01

    Recently, I wrote a paper discussing the lack of 'true' object-oriented programming language features in Ada 83, why one might desire them in Ada, and how they might be added in Ada 9X. The approach I took in this paper was to build the new object-oriented features of Ada 9X as much as possible on the basic constructs and philosophy of Ada 83. The object-oriented features proposed for Ada 9X, while different in detail, are based on the same kind of approach. Further consideration of this approach led me on a long reflection on the nature of object-oriented programming and its application to Ada. The results of this reflection, presented in this paper, show how a fairly natural object-oriented style can indeed be developed even in Ada 83. The exercise of developing this style is useful for at least three reasons: (1) it provides a useful style for programming object-oriented applications in Ada 83 until new features become available with Ada 9X; (2) it demystifies many of the mechanisms that seem to be 'magic' in most object-oriented programming languages by making them explicit; and (3) it points out areas that are and are not in need of change in Ada 83 to make object-oriented programming more natural in Ada 9X. In the next four sections I will address in turn the issues of object-oriented classes, mixins, self-reference and supertyping. The presentation is through a sequence of examples. This results in some overlap with that paper, but all the examples in the present paper are written entirely in Ada 83. I will return to considerations for Ada 9X in the last section of the paper.

  19. QUEST/Ada: Query utility environment for software testing of Ada

    NASA Technical Reports Server (NTRS)

    Brown, David B.

    1989-01-01

    Results of research and development efforts are presented for Task 1, Phase 2 of a general project entitled, The Development of a Program Analysis Environment for Ada. A prototype of the QUEST/Ada system was developed to collect data to determine the effectiveness of the rule-based testing paradigm. The prototype consists of five parts: the test data generator, the parser/scanner, the test coverage analyzer, a symbolic evaluator, and a data management facility, known as the Librarian. These components are discussed at length. Also presented is an experimental design for the evaluations, an overview of the project, and a schedule for its completion.

  20. Association of G22A and A4223C ADA1 gene polymorphisms and ADA activity with PCOS.

    PubMed

    Salehabadi, Mahshid; Farimani, Marzieh; Tavilani, Heidar; Ghorbani, Marzieh; Poormonsefi, Faranak; Poorolajal, Jalal; Shafiei, Gholamreza; Ghasemkhani, Neda; Khodadadi, Iraj

    2016-06-01

    Adenosine deaminase-1 (ADA1) regulates the concentration of adenosine as the main modulator of oocyte maturation. There is compelling evidence for the association of ADA1 gene polymorphisms with many diseases but the importance of ADA1 polymorphisms in polycystic ovary syndrome (PCOS) has not been studied before. This study investigates serum total ADA activity (tADA), ADA1 and ADA2 isoenzyme activities, and genotype and allele frequencies of G22A and A4223C polymorphisms in healthy and PCOS women. In this case-control study 200 PCOS patients and 200 healthy women were enrolled. Genomic DNA was extracted from whole blood and the PCR-RFLP technique was used to determine the G22A and A4223C variants. The genotype frequencies were calculated and the association between polymorphic genotypes and enzyme activities were determined. tADA activity was significantly lower in the PCOS group compared with the control group (27.76±6.0 vs. 39.63±7.48, respectively). PCOS patients also showed reduced activity of ADA1 and ADA2. PCOS was not associated with G22A polymorphism whereas AA, AC, and CC genotypes of A4223C polymorphism were found distributed differently between the control and the PCOS women where the C allele showed a strong protective role for PCOS (odds ratio=1.876, p=0.033). The present study for the first time showed that lower ADA activity may be involved in pathogenesis of PCOS by maintaining a higher concentration of adenosine affecting follicular growth. As a novel finding, we also showed great differences in genotype distribution and allele frequencies of A4223C polymorphism between groups indicating a protective role for C allele against PCOS. AbbreviationsADA: adenosine deaminase PCOS: polycystic ovary syndrome PCR-RFLP: polymerase chain reaction-restriction fragment length polymorphism tADA: total adenosine deaminase.

  1. Ada(R) Test and Verification System (ATVS)

    NASA Technical Reports Server (NTRS)

    Strelich, Tom

    1986-01-01

    The Ada Test and Verification System (ATVS) functional description and high level design are completed and summarized. The ATVS will provide a comprehensive set of test and verification capabilities specifically addressing the features of the Ada language, support for embedded system development, distributed environments, and advanced user interface capabilities. Its design emphasis was on effective software development environment integration and flexibility to ensure its long-term use in the Ada software development community.

  2. Software engineering and the role of Ada: Executive seminar

    NASA Technical Reports Server (NTRS)

    Freedman, Glenn B.

    1987-01-01

    The objective was to introduce the basic terminology and concepts of software engineering and Ada. The life cycle model is reviewed. The application of the goals and principles of software engineering is applied. An introductory understanding of the features of the Ada language is gained. Topics addressed include: the software crises; the mandate of the Space Station Program; software life cycle model; software engineering; and Ada under the software engineering umbrella.

  3. Towards a formal semantics for Ada 9X

    NASA Technical Reports Server (NTRS)

    Guaspari, David; Mchugh, John; Wolfgang, Polak; Saaltink, Mark

    1995-01-01

    The Ada 9X language precision team was formed during the revisions of Ada 83, with the goal of analyzing the proposed design, identifying problems, and suggesting improvements, through the use of mathematical models. This report defines a framework for formally describing Ada 9X, based on Kahn's 'natural semantics', and applies the framework to portions of the language. The proposals for exceptions and optimization freedoms are also analyzed, using a different technique.

  4. ART/Ada design project, phase 1: Project plan

    NASA Technical Reports Server (NTRS)

    Allen, Bradley P.

    1988-01-01

    The plan and schedule for Phase 1 of the Ada based ESBT Design Research Project is described. The main platform for the project is a DEC Ada compiler on VAX mini-computers and VAXstations running the Virtual Memory System (VMS) operating system. The Ada effort and lines of code are given in tabular form. A chart is given of the entire project life cycle.

  5. Ada and the rapid development lifecycle

    NASA Technical Reports Server (NTRS)

    Deforrest, Lloyd; Gref, Lynn

    1991-01-01

    JPL is under contract, through NASA, with the US Army to develop a state-of-the-art Command Center System for the US European Command (USEUCOM). The Command Center System will receive, process, and integrate force status information from various sources and provide this integrated information to staff officers and decision makers in a format designed to enhance user comprehension and utility. The system is based on distributed workstation class microcomputers, VAX- and SUN-based data servers, and interfaces to existing military mainframe systems and communication networks. JPL is developing the Command Center System utilizing an incremental delivery methodology called the Rapid Development Methodology with adherence to government and industry standards including the UNIX operating system, X Windows, OSF/Motif, and the Ada programming language. Through a combination of software engineering techniques specific to the Ada programming language and the Rapid Development Approach, JPL was able to deliver capability to the military user incrementally, with comparable quality and improved economies of projects developed under more traditional software intensive system implementation methodologies.

  6. ADA (adenosine deaminase) gene therapy enters the competition

    SciTech Connect

    Culliton, B.J.

    1990-08-31

    Around the world, some 70 children are members of a select and deadly club. Born with an immune deficiency so severe that they will die of infection unless their immune systems can be repaired, they have captured the attention of would-be gene therapists who believe that a handful of these kids--the 15 or 20 who lack functioning levels of the enzyme adenosine deaminase (ADA)--could be saved by a healthy ADA gene. A team of gene therapists is ready to put the theory to the test. In April 1987, a team of NIH researchers headed by R. Michael Blaese and W. French Anderson came up with the first formal protocol to introduce a healthy ADA gene into an unhealthy human. After 3 years of line-by-line scrutiny by five review committees, they have permission to go ahead. Two or three children will be treated in the next year, and will be infused with T lymphocytes carrying the gene for ADA. If the experiment works, the ADA gene will begin producing normal amounts of ADA. An interesting feature of ADA deficiency, that makes it ideal for initial gene studies, is that the amount of ADA one needs for a healthy immune system is quite variable. Hence, once inside a patient's T cells, the new ADA gene needs only to express the enzyme in moderate amounts. No precise gene regulation is necessary.

  7. Implementation of a production Ada project: The GRODY study

    NASA Technical Reports Server (NTRS)

    Godfrey, Sara; Brophy, Carolyn Elizabeth

    1989-01-01

    The use of the Ada language and design methodologies that encourage full use of its capabilities have a strong impact on all phases of the software development project life cycle. At the National Aeronautics and Space Administration/Goddard Space Flight Center (NASA/GSFC), the Software Engineering Laboratory (SEL) conducted an experiment in parallel development of two flight dynamics systems in FORTRAN and Ada. The differences observed during the implementation, unit testing, and integration phases of the two projects are described and the lessons learned during the implementation phase of the Ada development are outlined. Included are recommendations for future Ada development projects.

  8. Sharing the Dream: Is the ADA Accommodating All? A Report on the Americans with Disabilities Act.

    ERIC Educational Resources Information Center

    Foreman, Michael L.; Jefferson, Tricia; de La Viez, Barbara; Park, Jenny Kim; Reilly, Peter; Quarterman, Bernard

    This report, generated by a Congressional hearing, analyzes the goals intended for the Americans with Disabilities Act (ADA) and the impact on those it was intended to protect. It also discusses the practical effects of the ADA, recent Supreme Court decisions and judicial trends in ADA enforcement, substance abuse and the ADA, and the ADA's…

  9. Service dogs, psychiatric hospitalization, and the ADA.

    PubMed

    Muramatsu, Russ S; Thomas, Kelly Jones; Leong, Stephanie L; Ragukonis, Frank

    2015-01-01

    A service dog is defined as "any dog that is individually trained to do work or perform tasks for the benefit of an individual with a disability, including a physical, sensory, psychiatric, intellectual, or other mental disability." Some psychiatric patients may depend on a service dog for day-to-day functioning. The Americans with Disabilities Act (ADA) established certain rights and responsibilities for individuals with disabilities and health care providers. Psychiatric hospitalization of a patient with a service dog may pose a problem and involves balancing the requirement to provide safe and appropriate psychiatric care with the rights of individuals with disabilities. This Open Forum examines issues that arise in such circumstances, reviews the literature, and provides a foundation for the development of policies and procedures.

  10. A design for a reusable Ada library

    NASA Technical Reports Server (NTRS)

    Litke, John D.

    1986-01-01

    A goal of the Ada language standardization effort is to promote reuse of software, implying the existence of substantial software libraries and the storage/retrieval mechanisms to support them. A searching/cataloging mechanism is proposed that permits full or partial distribution of the database, adapts to a variety of searching mechanisms, permits a changine taxonomy with minimal disruption, and minimizes the requirement of specialized cataloger/indexer skills. The important observation is that key words serve not only as indexing mechanism, but also as an identification mechanism, especially via concatenation and as support for a searching mechanism. By deliberately separating these multiple uses, the modifiability and ease of growth that current libraries require, is achieved.

  11. Service dogs, psychiatric hospitalization, and the ADA.

    PubMed

    Muramatsu, Russ S; Thomas, Kelly Jones; Leong, Stephanie L; Ragukonis, Frank

    2015-01-01

    A service dog is defined as "any dog that is individually trained to do work or perform tasks for the benefit of an individual with a disability, including a physical, sensory, psychiatric, intellectual, or other mental disability." Some psychiatric patients may depend on a service dog for day-to-day functioning. The Americans with Disabilities Act (ADA) established certain rights and responsibilities for individuals with disabilities and health care providers. Psychiatric hospitalization of a patient with a service dog may pose a problem and involves balancing the requirement to provide safe and appropriate psychiatric care with the rights of individuals with disabilities. This Open Forum examines issues that arise in such circumstances, reviews the literature, and provides a foundation for the development of policies and procedures. PMID:25321094

  12. 49 CFR 37.123 - ADA paratransit eligibility: Standards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false ADA paratransit eligibility: Standards. 37.123 Section 37.123 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Paratransit as a Complement to Fixed Route Service § 37.123...

  13. The ADA and IDEA Basics: Inclusion of Children with Disabilities

    ERIC Educational Resources Information Center

    Motwani, Mona

    2007-01-01

    This article discusses the American with Disabilities Act (ADA) and the Individuals with Disabilities Education Act (IDEA). The ADA is a federal civil rights law that was passed in 1990 with the aim of securing equal rights for persons with disabilities in the employment, housing, government, transportation, and public accommodation contexts. It…

  14. Alma Flor Ada and the Quest for Change

    ERIC Educational Resources Information Center

    Manna, Anthony, L.; Hill, Janet; Kellogg, Kathy

    2004-01-01

    Alma Flor Ada, a folklorist, novelist, scholar, teacher, and children's book author has passionate dedication to education for social justice, equality, and peace. As a faculty member at the University of San Francisco, Ada has developed programs that help students and others transform their lives and has written several bilingual legends and…

  15. Communication and the ADA (Effective Communication and Accessibility).

    ERIC Educational Resources Information Center

    American Speech-Language-Hearing Association, Rockville, MD.

    This brief fact sheet addresses the following concerns about effective communication and accessibility under the Americans with Disabilities Act (ADA): requirements under the ADA for achieving effective communication (e.g., provision of necessary auxiliary communication aids and services); identification of necessary communication aids and…

  16. Artificial Intelligence in ADA: Pattern-Directed Processing. Final Report.

    ERIC Educational Resources Information Center

    Reeker, Larry H.; And Others

    To demonstrate to computer programmers that the programming language Ada provides superior facilities for use in artificial intelligence applications, the three papers included in this report investigate the capabilities that exist within Ada for "pattern-directed" programming. The first paper (Larry H. Reeker, Tulane University) is designed to…

  17. Translation and execution of distributed Ada programs - Is it still Ada?

    NASA Technical Reports Server (NTRS)

    Volz, Richard A.; Mudge, Trevor N.; Buzzard, Gregory D.; Krishnan, Padmanabhan

    1987-01-01

    Some of the fundamental issues and tradeoffs for distributed execution systems for the Ada language are examined. Steps that need to be taken to deal with heterogeneity of addressing program objects, of processing resources, and of the individual processor environment are considered. The ways in which program elements can be assigned are examined in the context of four issues: implied remote object access, object visibility and recursive execution, task termination problems, and distributed types.

  18. Simulation of the space station information system in Ada

    NASA Technical Reports Server (NTRS)

    Spiegel, James R.

    1986-01-01

    The Flexible Ada Simulation Tool (FAST) is a discrete event simulation language which is written in Ada. FAST has been used to simulate a number of options for ground data distribution of Space Station payload data. The fact that Ada language is used for implementation has allowed a number of useful interactive features to be built into FAST and has facilitated quick enhancement of its capabilities to support new modeling requirements. General simulation concepts are discussed, and how these concepts are implemented in FAST. The FAST design is discussed, and it is pointed out how the used of the Ada language enabled the development of some significant advantages over classical FORTRAN based simulation languages. The advantages discussed are in the areas of efficiency, ease of debugging, and ease of integrating user code. The specific Ada language features which enable these advances are discussed.

  19. The ADA at three years: a statute in flux.

    PubMed

    Coil, J H; Shapiro, L J

    1996-01-01

    In the three years since the Americans with Disabilities Act (ADA) was enacted, significant developments have occurred in the form of new administrative and judicial interpretations of the Act. The new guidelines and decisions will assist employers in complying with the ambiguous, and sometimes confusing, provisions of the ADA. Recent developments in areas such as the definition of a disability and the permissibility of medical inquiries, along with continuing developments in the areas of mental disabilities and defining reasonable accommodations, give employers insight into the obligations created by the ADA. These developments are a good starting point to understanding the ADA, but there is still a long way to go. This article surveys the recent developments in the law and examines the considerations that have become important to the Equal Employment Opportunity Commission and the courts in interpreting the ADA's provisions.

  20. First International Conference on Ada (R) Programming Language Applications for the NASA Space Station, volume 1

    NASA Technical Reports Server (NTRS)

    Bown, Rodney L. (Editor)

    1986-01-01

    Topics discussed include: test and verification; environment issues; distributed Ada issues; life cycle issues; Ada in Europe; management/training issues; common Ada interface set; and run time issues.

  1. ART/Ada design project, phase 1. Task 1 report: Overall design

    NASA Technical Reports Server (NTRS)

    Allen, Bradley P.

    1988-01-01

    The design methodology for the ART/Ada project is introduced, and the selected design for ART/Ada is described in detail. The following topics are included: object-oriented design, reusable software, documentation techniques, impact of Ada, design approach, and differences between ART-IM 1.5 and ART/Ada 1.0 prototype. Also, Ada generator and ART/Ada runtime systems are discussed.

  2. A proposed classification scheme for Ada-based software products

    NASA Technical Reports Server (NTRS)

    Cernosek, Gary J.

    1986-01-01

    As the requirements for producing software in the Ada language become a reality for projects such as the Space Station, a great amount of Ada-based program code will begin to emerge. Recognizing the potential for varying levels of quality to result in Ada programs, what is needed is a classification scheme that describes the quality of a software product whose source code exists in Ada form. A 5-level classification scheme is proposed that attempts to decompose this potentially broad spectrum of quality which Ada programs may possess. The number of classes and their corresponding names are not as important as the mere fact that there needs to be some set of criteria from which to evaluate programs existing in Ada. An exact criteria for each class is not presented, nor are any detailed suggestions of how to effectively implement this quality assessment. The idea of Ada-based software classification is introduced and a set of requirements from which to base further research and development is suggested.

  3. Integrity and security in an Ada runtime environment

    NASA Technical Reports Server (NTRS)

    Bown, Rodney L.

    1991-01-01

    A review is provided of the Formal Methods group discussions. It was stated that integrity is not a pure mathematical dual of security. The input data is part of the integrity domain. The group provided a roadmap for research. One item of the roadmap and the final position statement are closely related to the space shuttle and space station. The group's position is to use a safe subset of Ada. Examples of safe sets include the Army Secure Operating System and the Penelope Ada verification tool. It is recommended that a conservative attitude is required when writing Ada code for life and property critical systems.

  4. Visualization design and verification of Ada tasking using timing diagrams

    NASA Technical Reports Server (NTRS)

    Vidale, R. F.; Szulewski, P. A.; Weiss, J. B.

    1986-01-01

    The use of timing diagrams is recommended in the design and testing of multi-task Ada programs. By displaying the task states vs. time, timing diagrams can portray the simultaneous threads of data flow and control which characterize tasking programs. This description of the system's dynamic behavior from conception to testing is a necessary adjunct to other graphical techniques, such as structure charts, which essentially give a static view of the system. A series of steps is recommended which incorporates timing diagrams into the design process. Finally, a description is provided of a prototype Ada Execution Analyzer (AEA) which automates the production of timing diagrams from VAX/Ada debugger output.

  5. Mental disabilities under the ADA: a management rights approach.

    PubMed

    McDonald, J J; Kulick, F B; Creighton, M K

    1995-01-01

    While numerous sources have focused on employee rights and employer obligations under the Americans with Disabilities Act, this article will emphasize employer rights with respect to mental disabilities under the ADA. Specifically, it addresses the ADA's definition of "mental disability," the right of employers to screen job applicants in spite of the ADA, the conditions under which an employer may require an employee to undergo a "fitness for duty" examination, and the limits of the duty to "reasonably accommodate" an employee with a mental disability.

  6. Software Engineering Laboratory (SEL) Ada performance study report

    NASA Technical Reports Server (NTRS)

    Booth, Eric W.; Stark, Michael E.

    1991-01-01

    The goals of the Ada Performance Study are described. The methods used are explained. Guidelines for future Ada development efforts are given. The goals and scope of the study are detailed, and the background of Ada development in the Flight Dynamics Division (FDD) is presented. The organization and overall purpose of each test are discussed. The purpose, methods, and results of each test and analyses of these results are given. Guidelines for future development efforts based on the analysis of results from this study are provided. The approach used on the performance tests is discussed.

  7. Applications of an architecture design and assessment system (ADAS)

    NASA Technical Reports Server (NTRS)

    Gray, F. Gail; Debrunner, Linda S.; White, Tennis S.

    1988-01-01

    A new Architecture Design and Assessment System (ADAS) tool package is introduced, and a range of possible applications is illustrated. ADAS was used to evaluate the performance of an advanced fault-tolerant computer architecture in a modern flight control application. Bottlenecks were identified and possible solutions suggested. The tool was also used to inject faults into the architecture and evaluate the synchronization algorithm, and improvements are suggested. Finally, ADAS was used as a front end research tool to aid in the design of reconfiguration algorithms in a distributed array architecture.

  8. Ada and software management in NASA: Symposium/forum

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The promises of Ada to improve software productivity and quality, and the claims that a transition to Ada would require significant changes in NASA's training programs and ways of doing business were investigated. The study assesses the agency's ongoing and planned Ada activities. A series of industry representatives (Computer Sciences Corporation, General Electric Aerospace, McDonnell Douglas Space Systems Company, TRW, Lockheed, and Boeing) reviewed the recommendations and assessed their impact from the Company's perspective. The potential effects on NASA programs were then discussed.

  9. QUEST/Ada (Query Utility Environment for Software Testing of Ada): The development of a prgram analysis environment for Ada, task 1, phase 2

    NASA Technical Reports Server (NTRS)

    Brown, David B.

    1990-01-01

    The results of research and development efforts are described for Task one, Phase two of a general project entitled The Development of a Program Analysis Environment for Ada. The scope of this task includes the design and development of a prototype system for testing Ada software modules at the unit level. The system is called Query Utility Environment for Software Testing of Ada (QUEST/Ada). The prototype for condition coverage provides a platform that implements expert system interaction with program testing. The expert system can modify data in the instrument source code in order to achieve coverage goals. Given this initial prototype, it is possible to evaluate the rule base in order to develop improved rules for test case generation. The goals of Phase two are the following: (1) to continue to develop and improve the current user interface to support the other goals of this research effort (i.e., those related to improved testing efficiency and increased code reliable); (2) to develop and empirically evaluate a succession of alternative rule bases for the test case generator such that the expert system achieves coverage in a more efficient manner; and (3) to extend the concepts of the current test environment to address the issues of Ada concurrency.

  10. The development of a program analysis environment for Ada

    NASA Technical Reports Server (NTRS)

    Brown, David B.; Carlisle, Homer W.; Chang, Kai-Hsiung; Cross, James H.; Deason, William H.; Haga, Kevin D.; Huggins, John R.; Keleher, William R. A.; Starke, Benjamin B.; Weyrich, Orville R.

    1989-01-01

    A unit level, Ada software module testing system, called Query Utility Environment for Software Testing of Ada (QUEST/Ada), is described. The project calls for the design and development of a prototype system. QUEST/Ada design began with a definition of the overall system structure and a description of component dependencies. The project team was divided into three groups to resolve the preliminary designs of the parser/scanner: the test data generator, and the test coverage analyzer. The Phase 1 report is a working document from which the system documentation will evolve. It provides history, a guide to report sections, a literature review, the definition of the system structure and high level interfaces, descriptions of the prototype scope, the three major components, and the plan for the remainder of the project. The appendices include specifications, statistics, two papers derived from the current research, a preliminary users' manual, and the proposal and work plan for Phase 2.

  11. The Adam language: Ada extended with support for multiway activities

    NASA Technical Reports Server (NTRS)

    Charlesworth, Arthur

    1993-01-01

    The Adam language is an extension of Ada that supports multiway activities, which are cooperative activities involving two or more processes. This support is provided by three new constructs: diva procedures, meet statements, and multiway accept statements. Diva procedures are recursive generic procedures having a particular restrictive syntax that facilitates translation for parallel computers. Meet statements and multiway accept statements provide two ways to express a multiway rendezvous, which is an n-way rendezvous generalizing Ada's 2-way rendezvous. While meet statements tend to have simpler rules than multiway accept statements, the latter approach is a more straightforward extension of Ada. The only nonnull statements permitted within meet statements and multiway accept statements are calls on instantiated diva procedures. A call on an instantiated diva procedure is also permitted outside a multiway rendezvous; thus sequential Adam programs using diva procedures can be written. Adam programs are translated into Ada programs appropriate for use on parallel computers.

  12. A report on NASA software engineering and Ada training requirements

    NASA Technical Reports Server (NTRS)

    Legrand, Sue; Freedman, Glenn B.; Svabek, L.

    1987-01-01

    NASA's software engineering and Ada skill base are assessed and information that may result in new models for software engineering, Ada training plans, and curricula are provided. A quantitative assessment which reflects the requirements for software engineering and Ada training across NASA is provided. A recommended implementation plan including a suggested curriculum with associated duration per course and suggested means of delivery is also provided. The distinction between education and training is made. Although it was directed to focus on NASA's need for the latter, the key relationships to software engineering education are also identified. A rationale and strategy for implementing a life cycle education and training program are detailed in support of improved software engineering practices and the transition to Ada.

  13. Image simulation using LOCUS

    SciTech Connect

    Strachan, J.D.; Roberts, J.A.

    1989-09-01

    The LOCUS data base program has been used to simulate images and to solve simple equations. This has been accomplished by making each record (which normally would represent a data entry)represent sequenced or random number pairs.

  14. Designing with Ada for satellite simulation: A case study

    NASA Technical Reports Server (NTRS)

    Agresti, W. W.; Church, V. E.; Card, D. N.; Lo, P. L.

    1986-01-01

    A FORTRAN oriented and an Ada oriented design for the same system are compared to learn whether an essentially different design was produced using Ada. The designs were produced by an experiment that involves the parallel development of software for a spacecraft dynamics simulator. Design differences are identified in the use of abstractions, system structure, and simulator operations. Although the designs were vastly different, this result may be influenced by some special characteristics discussed.

  15. Designing with Ada for satellite simulation: A case study

    NASA Technical Reports Server (NTRS)

    Agresti, William W.; Church, Victor E.; Card, David N.; Lo, P. L.

    1986-01-01

    A FORTRAN-operated and an Ada-oriented design for the same system are compared to learn whether an essentially different design was produced using Ada. The designs were produced by an experiment that involves the parallel development of software for a spacecraft dynamics simulator. Design differences are identified in the use of abstractions, system structure, and simulator operations. Although the designs were significantly different, this result may be influenced by some special characteristics discussed.

  16. GRASP/Ada: Graphical Representations of Algorithms, Structures, and Processes for Ada. The development of a program analysis environment for Ada: Reverse engineering tools for Ada, task 2, phase 3

    NASA Technical Reports Server (NTRS)

    Cross, James H., II

    1991-01-01

    The main objective is the investigation, formulation, and generation of graphical representations of algorithms, structures, and processes for Ada (GRASP/Ada). The presented task, in which various graphical representations that can be extracted or generated from source code are described and categorized, is focused on reverse engineering. The following subject areas are covered: the system model; control structure diagram generator; object oriented design diagram generator; user interface; and the GRASP library.

  17. Compiling knowledge-based systems specified in KEE to Ada

    NASA Technical Reports Server (NTRS)

    Filman, Robert E.; Feldman, Roy D.

    1991-01-01

    The first year of the PrKAda project is recounted. The primary goal was to develop a system for delivering Artificial Intelligence applications developed in the ProKappa system in a pure-Ada environment. The following areas are discussed: the ProKappa core and ProTalk programming language; the current status of the implementation; the limitations and restrictions of the current system; and the development of Ada-language message handlers in the ProKappa environment.

  18. Programming in a proposed 9X distributed Ada

    NASA Technical Reports Server (NTRS)

    Waldrop, Raymond S.; Volz, Richard A.; Goldsack, Stephen J.; Holzbach-Valero, A. A.

    1991-01-01

    The studies of the proposed Ada 9X constructs for distribution, now referred to as AdaPT are reported. The goals for this time period were to revise the chosen example scenario and to begin studying about how the proposed constructs might be implemented. The example scenario chosen is the Submarine Combat Information Center (CIC) developed by IBM for the Navy. The specification provided by IBM was preliminary and had several deficiencies. To address these problems, some changes to the scenario specification were made. Some of the more important changes include: (1) addition of a system database management function; (2) addition of a fourth processing unit to the standard resources; (3) addition of an operator console interface function; and (4) removal of the time synchronization function. To implement the CIC scenario in AdaPT, the decided strategy were publics, partitions, and nodes. The principle purpose for implementing the CIC scenario was to demonstrate how the AdaPT constructs interact with the program structure. While considering ways that the AdaPt constructs might be translated to Ada 83, it was observed that the partition construct could reasonably be modeled as an abstract data type. Although this gives a useful method of modeling partitions, it does not at all address the configuration aspects on the node construct.

  19. Examining the reliability of ADAS-Cog change scores.

    PubMed

    Grochowalski, Joseph H; Liu, Ying; Siedlecki, Karen L

    2016-09-01

    The purpose of this study was to estimate and examine ways to improve the reliability of change scores on the Alzheimer's Disease Assessment Scale, Cognitive Subtest (ADAS-Cog). The sample, provided by the Alzheimer's Disease Neuroimaging Initiative, included individuals with Alzheimer's disease (AD) (n = 153) and individuals with mild cognitive impairment (MCI) (n = 352). All participants were administered the ADAS-Cog at baseline and 1 year, and change scores were calculated as the difference in scores over the 1-year period. Three types of change score reliabilities were estimated using multivariate generalizability. Two methods to increase change score reliability were evaluated: reweighting the subtests of the scale and adding more subtests. Reliability of ADAS-Cog change scores over 1 year was low for both the AD sample (ranging from .53 to .64) and the MCI sample (.39 to .61). Reweighting the change scores from the AD sample improved reliability (.68 to .76), but lengthening provided no useful improvement for either sample. The MCI change scores had low reliability, even with reweighting and adding additional subtests. The ADAS-Cog scores had low reliability for measuring change. Researchers using the ADAS-Cog should estimate and report reliability for their use of the change scores. The ADAS-Cog change scores are not recommended for assessment of meaningful clinical change. PMID:26708116

  20. Hydraulic Capacity of an ADA Compliant Street Drain Grate

    SciTech Connect

    Lottes, Steven A.; Bojanowski, Cezary

    2015-09-01

    Resurfacing of urban roads with concurrent repairs and replacement of sections of curb and sidewalk may require pedestrian ramps that are compliant with the American Disabilities Act (ADA), and when street drains are in close proximity to the walkway, ADA compliant street grates may also be required. The Minnesota Department of Transportation ADA Operations Unit identified a foundry with an available grate that meets ADA requirements. Argonne National Laboratory’s Transportation Research and Analysis Computing Center used full scale three dimensional computational fluid dynamics to determine the performance of the ADA compliant grate and compared it to that of a standard vane grate. Analysis of a parametric set of cases was carried out, including variation in longitudinal, gutter, and cross street slopes and the water spread from the curb. The performance of the grates was characterized by the fraction of the total volume flow approaching the grate from the upstream that was captured by the grate and diverted into the catch basin. The fraction of the total flow entering over the grate from the side and the fraction of flow directly over a grate diverted into the catch basin were also quantities of interest that aid in understanding the differences in performance of the grates. The ADA compliant grate performance lagged that of the vane grate, increasingly so as upstream Reynolds number increased. The major factor leading to the performance difference between the two grates was the fraction of flow directly over the grates that is captured by the grates.

  1. Compiling knowledge-based systems from KEE to Ada

    NASA Technical Reports Server (NTRS)

    Filman, Robert E.; Bock, Conrad; Feldman, Roy

    1990-01-01

    The dominant technology for developing AI applications is to work in a multi-mechanism, integrated, knowledge-based system (KBS) development environment. Unfortunately, systems developed in such environments are inappropriate for delivering many applications - most importantly, they carry the baggage of the entire Lisp environment and are not written in conventional languages. One resolution of this problem would be to compile applications from complex environments to conventional languages. Here the first efforts to develop a system for compiling KBS developed in KEE to Ada (trademark). This system is called KATYDID, for KEE/Ada Translation Yields Development Into Delivery. KATYDID includes early prototypes of a run-time KEE core (object-structure) library module for Ada, and translation mechanisms for knowledge structures, rules, and Lisp code to Ada. Using these tools, part of a simple expert system was compiled (not quite automatically) to run in a purely Ada environment. This experience has given us various insights on Ada as an artificial intelligence programming language, potential solutions of some of the engineering difficulties encountered in early work, and inspiration on future system development.

  2. Forward vehicle detection using cluster-based AdaBoost

    NASA Astrophysics Data System (ADS)

    Baek, Yeul-Min; Kim, Whoi-Yul

    2014-10-01

    A camera-based forward vehicle detection method with range estimation for forward collision warning system (FCWS) is presented. Previous vehicle detection methods that use conventional classifiers are not robust in a real driving environment because they lack the effectiveness of classifying vehicle samples with high intraclass variation and noise. Therefore, an improved AdaBoost, named cluster-based AdaBoost (C-AdaBoost), for classifying noisy samples along with a forward vehicle detection method are presented in this manuscript. The experiments performed consist of two parts: performance evaluations of C-AdaBoost and forward vehicle detection. The proposed C-AdaBoost shows better performance than conventional classification algorithms on the synthetic as well as various real-world datasets. In particular, when the dataset has more noisy samples, C-AdaBoost outperforms conventional classification algorithms. The proposed method is also tested with an experimental vehicle on a proving ground and on public roads, ˜62 km in length. The proposed method shows a 97% average detection rate and requires only 9.7 ms per frame. The results show the reliability of the proposed method FCWS in terms of both detection rate and processing time.

  3. Proceedings of the third international IEEE conference on Ada applications and environments

    SciTech Connect

    Not Available

    1988-01-01

    These proceedings collect papers on software applications. Topics include: An interleaving symbolic execution approach for the formal verification of Ada programs with tasking, fault-tolerant Ada software, object-oriented frameworks for Ada, and generating multitasking Ada programs from high-level specifications.

  4. Two Arabidopsis orthologs of the transcriptional coactivator ADA2 have distinct biological functions.

    PubMed

    Hark, Amy T; Vlachonasios, Konstantinos E; Pavangadkar, Kanchan A; Rao, Sumana; Gordon, Hillary; Adamakis, Ioannis-Dimosthenis; Kaldis, Athanasios; Thomashow, Michael F; Triezenberg, Steven J

    2009-02-01

    Histone acetylation is an example of covalent modification of chromatin structure that has the potential to regulate gene expression. Gcn5 is a prototypical histone acetyltransferase that associates with the transcriptional coactivator Ada2. In Arabidopsis, two genes encode proteins that resemble yeast ADA2 and share approximately 45% amino acid sequence identity. We previously reported that plants harboring a T-DNA insertion in the ADA2b gene display a dwarf phenotype with developmental defects in several organs. Here we describe T-DNA insertion alleles in the ADA2a gene, which result in no dramatic growth or developmental phenotype. Both ADA2a and ADA2b are expressed in a variety of plant tissues; moreover, expression of ADA2a from a constitutive promoter fails to complement the ada2b-1 mutant phenotype, consistent with the hypothesis that the two proteins have distinct biochemical roles. To further probe the cellular roles of ADA2a and ADA2b, we studied the response of the transcriptional coactivator mutants to abiotic stress. Although ada2b seedlings display hypersensitivity to salt and abscisic acid and altered responses to low temperature stress, the responses of ada2a seedlings to abiotic stress generally parallel those of wildtype plants. Intriguingly, ada2a;ada2b double mutant plants display an intermediate, gcn5-like phenotype, suggesting that ADA2a and ADA2b each work independently with GCN5 to affect genome function in Arabidopsis.

  5. Cultural Diversity and the ADA. Implementing the Americans with Disabilities Act.

    ERIC Educational Resources Information Center

    Bruyere, Susanne M.; Hoying, Joyce

    One of a series of guides on implementing the Americans with Disabilities Act (ADA), this guide focuses on cultural diversity and the ADA. First, the major components of the ADA are summarized. This is followed by discussion of employer considerations in addressing cultural diversity issues and implications of the ADA, such as diversity…

  6. ART/Ada design project, phase 1. Task 3 report: Test plan

    NASA Technical Reports Server (NTRS)

    Allen, Bradley P.

    1988-01-01

    The plan is described for the integrated testing and benchmark of Phase Ada based ESBT Design Research Project. The integration testing is divided into two phases: (1) the modules that do not rely on the Ada code generated by the Ada Generator are tested before the Ada Generator is implemented; and (2) all modules are integrated and tested with the Ada code generated by the Ada Generator. Its performance and size as well as its functionality is verified in this phase. The target platform is a DEC Ada compiler on VAX mini-computers and VAX stations running the VMS operating system.

  7. AdaNET phase 0 support for the AdaNET Dynamic Software Inventory (DSI) management system prototype. Catalog of available reusable software components

    NASA Technical Reports Server (NTRS)

    Hanley, Lionel

    1989-01-01

    The Ada Software Repository is a public-domain collection of Ada software and information. The Ada Software Repository is one of several repositories located on the SIMTEL20 Defense Data Network host computer at White Sands Missile Range, and available to any host computer on the network since 26 November 1984. This repository provides a free source for Ada programs and information. The Ada Software Repository is divided into several subdirectories. These directories are organized by topic, and their names and a brief overview of their topics are contained. The Ada Software Repository on SIMTEL20 serves two basic roles: to promote the exchange and use (reusability) of Ada programs and tools (including components) and to promote Ada education.

  8. Recombinant Inbred Strain and Interspecific Backcross Analysis of Molecular Markers Flanking the Murine Agouti Coat Color Locus

    PubMed Central

    Siracusa, L. D.; Buchberg, A. M.; Copeland, N. G.; Jenkins, N. A.

    1989-01-01

    Recombinant inbred strain and interspecific backcross mice were used to create a molecular genetic linkage map of the distal portion of mouse chromosome 2. The orientation and distance of the Ada, Emv-13, Emv-15, Hck-1, Il-1a, Pck-1, Psp, Src-1 and Svp-1 loci from the β(2)-microglobulin locus and the agouti locus were established. Our mapping results have provided the identification of molecular markers both proximal and distal to the agouti locus. The recombinants obtained provide valuable resources for determining the direction of chromosome walking experiments designed to clone sequences at the agouti locus. Comparisons between the mouse and human genome maps suggest that the human homolog of the agouti locus resides on human chromosome 20q. Three loci not present on mouse chromosome 2 were also identified and were provisionally named Psp-2, Hck-2 and Hck-3. The Psp-2 locus maps to mouse chromosome 14. The Hck-2 locus maps near the centromere of mouse chromosome 4 and may identify the Lyn locus. The Hck-3 locus maps near the distal end of mouse chromosome 4 and may identify the Lck locus. PMID:2759422

  9. Toward real-time performance benchmarks for Ada

    NASA Technical Reports Server (NTRS)

    Clapp, Russell M.; Duchesneau, Louis; Volz, Richard A.; Mudge, Trevor N.; Schultze, Timothy

    1986-01-01

    The issue of real-time performance measurements for the Ada programming language through the use of benchmarks is addressed. First, the Ada notion of time is examined and a set of basic measurement techniques are developed. Then a set of Ada language features believed to be important for real-time performance are presented and specific measurement methods discussed. In addition, other important time related features which are not explicitly part of the language but are part of the run-time related features which are not explicitly part of the language but are part of the run-time system are also identified and measurement techniques developed. The measurement techniques are applied to the language and run-time system features and the results are presented.

  10. Transparent Ada rendezvous in a fault tolerant distributed system

    NASA Technical Reports Server (NTRS)

    Racine, Roger

    1986-01-01

    There are many problems associated with distributing an Ada program over a loosely coupled communication network. Some of these problems involve the various aspects of the distributed rendezvous. The problems addressed involve supporting the delay statement in a selective call and supporting the else clause in a selective call. Most of these difficulties are compounded by the need for an efficient communication system. The difficulties are compounded even more by considering the possibility of hardware faults occurring while the program is running. With a hardware fault tolerant computer system, it is possible to design a distribution scheme and communication software which is efficient and allows Ada semantics to be preserved. An Ada design for the communications software of one such system will be presented, including a description of the services provided in the seven layers of an International Standards Organization (ISO) Open System Interconnect (OSI) model communications system. The system capabilities (hardware and software) that allow this communication system will also be described.

  11. ADA plaintiff must show AIDS limits major life activities.

    PubMed

    1998-05-15

    In a rare case, a Federal court ruled that AIDS does not automatically qualify a plaintiff for legal protection under the Americans with Disabilities Act (ADA). [Name removed], an Illinois Wal-Mart stock clerk, was fired weeks after telling the store's general manager of his HIV status. [Name removed] alleges that the firing was due solely to his disease. Wal-Mart contends that [name removed] was fired for sexually harassing a co-worker, and says that since [name removed] was asymptomatic and asked for no accommodations, he does not qualify for ADA protection. Magistrate Morton Denlow agreed, saying that [name removed] raised no genuine issues about whether the ADA should protect him. A trial is scheduled for May. PMID:11365337

  12. State prisons are covered by ADA, 7th Circuit rules.

    PubMed

    1997-07-25

    Prison inmate [name removed] sued the Indiana Department of Corrections, claiming it violated the Americans with Disabilities Act (ADA) by denying him access to education programs, the library, and the dining hall because he is blind. The 7th U.S. Circuit Court of Appeals rejected the district court's decision to dismiss the case based on the grounds that the ADA does not apply to prison inmates. The court held that the Department of Corrections cannot exclude an inmate with a disability from prison programs unless the accommodation caused an undue burden on the system. PMID:11364516

  13. GRASP/Ada (Graphical Representations of Algorithms, Structures, and Processes for Ada): The development of a program analysis environment for Ada. Reverse engineering tools for Ada, task 1, phase 2

    NASA Technical Reports Server (NTRS)

    Cross, James H., II

    1990-01-01

    The study, formulation, and generation of structures for Ada (GRASP/Ada) are discussed in this second phase report of a three phase effort. Various graphical representations that can be extracted or generated from source code are described and categorized with focus on reverse engineering. The overall goal is to provide the foundation for a CASE (computer-aided software design) environment in which reverse engineering and forward engineering (development) are tightly coupled. Emphasis is on a subset of architectural diagrams that can be generated automatically from source code with the control structure diagram (CSD) included for completeness.

  14. STGT program: Ada coding and architecture lessons learned

    NASA Technical Reports Server (NTRS)

    Usavage, Paul; Nagurney, Don

    1992-01-01

    STGT (Second TDRSS Ground Terminal) is currently halfway through the System Integration Test phase (Level 4 Testing). To date, many software architecture and Ada language issues have been encountered and solved. This paper, which is the transcript of a presentation at the 3 Dec. meeting, attempts to define these lessons plus others learned regarding software project management and risk management issues, training, performance, reuse, and reliability. Observations are included regarding the use of particular Ada coding constructs, software architecture trade-offs during the prototyping, development and testing stages of the project, and dangers inherent in parallel or concurrent systems, software, hardware, and operations engineering.

  15. V Olimpíada Brasileira de Astronomia

    NASA Astrophysics Data System (ADS)

    Villas da Rocha, J. F.; Canalle, J. B. G.; Wuesnche, C. A.; de Medeiros, J. R., Silva, A. V. R.; Lavouras, D. F.; Dottori, H. A.; Maia, M. A. G.; Vieira Martins, R.; Poppe, P. C. R.

    2003-08-01

    Neste trabalho apresentamos os resultados da V Olimpíada Brasileira de Astronomia, a qual ocorreu em 11/05/2002 em todos os estabelecimentos de ensino fundamental ou médio previamente cadastrados. Participaram do evento 60.338 alunos distribuídos por 1469 escolas pertencentes a todos os Estados brasileiros. Uma equipe de 5 alunos foi escolhida para representar o Brasil na VII Olimpíada Internacional de Astronomia que ocorreu na Rússia em 2002 e dois de nossos alunos ganharam a medalha de bronze naquele evento.

  16. An Ada run-time control architecture for telerobots

    NASA Technical Reports Server (NTRS)

    Balaram, J.; Rodriguez, G.

    1987-01-01

    This paper describes the architecture and Ada language implementation of a process-level run-time control subystem for the Jet Propulsion Laboratory (JPL) telerobot system. The concept of run-time control in a combined robot-teleoperation environment is examined and the telerobot system at JPL is described. An Ada language implementation of the JPL Telerobot Run-Time Controller (RTC) is described by highlighting the functional behavior of the subsystem, defining the internal modules, and providing a functional flow time sequence of internal module activity.

  17. Formal methods in the design of Ada 1995

    NASA Technical Reports Server (NTRS)

    Guaspari, David

    1995-01-01

    Formal, mathematical methods are most useful when applied early in the design and implementation of a software system--that, at least, is the familiar refrain. I will report on a modest effort to apply formal methods at the earliest possible stage, namely, in the design of the Ada 95 programming language itself. This talk is an 'experience report' that provides brief case studies illustrating the kinds of problems we worked on, how we approached them, and the extent (if any) to which the results proved useful. It also derives some lessons and suggestions for those undertaking future projects of this kind. Ada 95 is the first revision of the standard for the Ada programming language. The revision began in 1988, when the Ada Joint Programming Office first asked the Ada Board to recommend a plan for revising the Ada standard. The first step in the revision was to solicit criticisms of Ada 83. A set of requirements for the new language standard, based on those criticisms, was published in 1990. A small design team, the Mapping Revision Team (MRT), became exclusively responsible for revising the language standard to satisfy those requirements. The MRT, from Intermetrics, is led by S. Tucker Taft. The work of the MRT was regularly subject to independent review and criticism by a committee of distinguished Reviewers and by several advisory teams--for example, the two User/Implementor teams, each consisting of an industrial user (attempting to make significant use of the new language on a realistic application) and a compiler vendor (undertaking, experimentally, to modify its current implementation in order to provide the necessary new features). One novel decision established the Language Precision Team (LPT), which investigated language proposals from a mathematical point of view. The LPT applied formal mathematical analysis to help improve the design of Ada 95 (e.g., by clarifying the language proposals) and to help promote its acceptance (e.g., by identifying a

  18. Genome-wide Mapping of the Coactivator Ada2p Yields Insight into the Functional Roles of SAGA/ADA Complex in Candida albicans

    PubMed Central

    Sellam, Adnane; Askew, Christopher; Epp, Elias; Lavoie, Hugo; Whiteway, Malcolm

    2009-01-01

    The SAGA/ADA coactivator complex, which regulates numerous cellular processes by coordinating histone acetylation, is widely conserved throughout eukaryotes, and analysis of the Candida albicans genome identifies the components of this complex in the fungal pathogen. We investigated the multiple functions of SAGA/ADA in C. albicans by determining the genome-wide occupancy of Ada2p using chromatin immunoprecipitation (ChIP). Ada2p is recruited to 200 promoters upstream of genes involved in different stress-response functions and metabolic processes. Phenotypic and transcriptomic analysis of ada2 mutant showed that Ada2p is required for the responses to oxidative stress, as well as to treatments with tunicamycin and fluconazole. Ada2p recruitment to the promoters of oxidative resistance genes is mediated by the transcription factor Cap1p, and coactivator function were also established for Gal4p, which recruits Ada2p to the promoters of glycolysis and pyruvate metabolism genes. Cooccupancy of Ada2p and the drug resistance regulator Mrr1p on the promoters of core resistance genes characterizing drug resistance in clinical strains was also demonstrated. Ada2p recruitment to the promoters of these genes were shown to be completely dependent on Mrr1p. Furthermore, ADA2 deletion causes a decrease in H3K9 acetylation levels of target genes, thus illustrating its importance for histone acetyl transferase activity. PMID:19279142

  19. The development of a program analysis environment for Ada: Reverse engineering tools for Ada. Final Report, 1 Jun. 1990 - 30 Sep. 1991

    SciTech Connect

    Cross, J.H. II.

    1991-09-01

    The Graphical Representations of Algorithms, Structures, and Processes for Ada (GRASP/Ada) has successfully created and prototyped a new algorithm level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and thus improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under the Virtual Memory System (VMS) on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. In Phase 3 of the project, the prototype was prepared for limited distribution (GRASP/Ada Version 3.0) to facilitate evaluation. The user interface was extensively reworked. The current prototype provides the capability for the user to generate CSD from Ada source code in a reverse engineering mode with a level of flexibility suitable for practical application.

  20. The development of an Ada programming support environment database: SEAD (Software Engineering and Ada Database), user's manual

    NASA Technical Reports Server (NTRS)

    Liaw, Morris; Evesson, Donna

    1988-01-01

    This is a manual for users of the Software Engineering and Ada Database (SEAD). SEAD was developed to provide an information resource to NASA and NASA contractors with respect to Ada-based resources and activities that are available or underway either in NASA or elsewhere in the worldwide Ada community. The sharing of such information will reduce the duplication of effort while improving quality in the development of future software systems. The manual describes the organization of the data in SEAD, the user interface from logging in to logging out, and concludes with a ten chapter tutorial on how to use the information in SEAD. Two appendices provide quick reference for logging into SEAD and using the keyboard of an IBM 3270 or VT100 computer terminal.

  1. Techniques and implementation of the embedded rule-based expert system using Ada

    NASA Technical Reports Server (NTRS)

    Liberman, Eugene M.; Jones, Robert E.

    1991-01-01

    Ada is becoming an increasingly popular programming language for large Government-funded software projects. Ada with its portability, transportability, and maintainability lends itself well to today's complex programming environment. In addition, expert systems have also assured a growing role in providing human-like reasoning capability and expertise for computer systems. The integration of expert system technology with Ada programming language, specifically a rule-based expert system using an ART-Ada (Automated Reasoning Tool for Ada) system shell is discussed. The NASA Lewis Research Center was chosen as a beta test site for ART-Ada. The test was conducted by implementing the existing Autonomous Power EXpert System (APEX), a Lisp-base power expert system, in ART-Ada. Three components, the rule-based expert system, a graphics user interface, and communications software make up SMART-Ada (Systems fault Management with ART-Ada). The main objective, to conduct a beta test on the ART-Ada rule-based expert system shell, was achieved. The system is operational. New Ada tools will assist in future successful projects. ART-Ada is one such tool and is a viable alternative to the straight Ada code when an application requires a rule-based or knowledge-based approach.

  2. ADA and multi-microprocessor real-time simulation

    NASA Technical Reports Server (NTRS)

    Feyock, S.; Collins, W. R.

    1983-01-01

    The selection of a high-order programming language for a real-time distributed network simulation is described. The additional problem of implementing a language on a possibly changing network is addressed. The recently designed language ADA (trademarked by DoD) was chosen since it provides the best model of the underlying application to be simulated.

  3. The ADA and Persons with Cognitive Disabilities. Trainer's Curriculum.

    ERIC Educational Resources Information Center

    State Univ. of New York, Ithaca. School of Industrial and Labor Relations at Cornell Univ.

    This comprehensive trainer's guide and participant manual are designed to provide a planning process through which training programs on the Americans with Disabilities Act (ADA) and its implications for persons with cognitive disabilities can be developed and delivered in a systematic way. Module 1 of the trainer's guide, "Planning and…

  4. Software Engineering Laboratory Ada performance study: Results and implications

    NASA Technical Reports Server (NTRS)

    Booth, Eric W.; Stark, Michael E.

    1992-01-01

    The SEL is an organization sponsored by NASA/GSFC to investigate the effectiveness of software engineering technologies applied to the development of applications software. The SEL was created in 1977 and has three organizational members: NASA/GSFC, Systems Development Branch; The University of Maryland, Computer Sciences Department; and Computer Sciences Corporation, Systems Development Operation. The goals of the SEL are as follows: (1) to understand the software development process in the GSFC environments; (2) to measure the effect of various methodologies, tools, and models on this process; and (3) to identify and then to apply successful development practices. The activities, findings, and recommendations of the SEL are recorded in the Software Engineering Laboratory Series, a continuing series of reports that include the Ada Performance Study Report. This paper describes the background of Ada in the Flight Dynamics Division (FDD), the objectives and scope of the Ada Performance Study, the measurement approach used, the performance tests performed, the major test results, and the implications for future FDD Ada development efforts.

  5. Section 504/ADA: Guidelines for Educators and Administrators. Revised.

    ERIC Educational Resources Information Center

    Utah State Office of Education, Salt Lake City.

    This document presents the Utah State Department of Education's guidelines to Section 504 of the Rehabilitation Act and the Americans with Disabilities Act (ADA). The guidelines specifically address Subparts D and E of the regulations for Section 504, which deal with education. An introduction offers examples of discriminatory acts by school…

  6. The Impact of Business Size on Employer ADA Response

    ERIC Educational Resources Information Center

    Bruyere, Susanne M.; Erickson, William A.; VanLooy, Sara A.

    2006-01-01

    More than 10 years have passed since the employment provisions of the Americans with Disabilities Act of 1990 (ADA) came into effect for employers of 15 or more employees. Americans with disabilities continue to be more unemployed and underemployed than their nondisabled peers. Small businesses, with fewer than 500 employees, continue to be the…

  7. Learn about the ADA in Your Local Library.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC. Civil Rights Div.

    This bibliography lists 90 documents contained within the Americans with Disabilities Act (ADA) Information File, which has been sent to 15,000 libraries across the country. The listing is organized into the following categories: laws and regulations (eight documents), technical assistance manuals and highlights (nine documents), question and…

  8. Section 504/ADA: Guidelines for Educators in Kansas. Revised.

    ERIC Educational Resources Information Center

    Miller, Joan; Bieker, Rod; Copenhaver, John

    This document presents the Kansas State Department of Education's guidelines to Section 504 of the Rehabilitation Act and the Americans with Disabilities Act (ADA). The guidelines specifically address Subparts A, B, C, and D of the regulations for Section 504 which deal with general provisions, employment practices, accessibility and education. An…

  9. [Section] 504/ADA Student Issues: The Latest and the Greatest.

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    Recent case law within and outside the school context has revised or refined various concepts concerning eligibility and other K-12 issues under Section 504 and the Americans with Disabilities Act (ADA). Ten case lessons are described in this paper, seven of which are: (1) The frame of reference for determining "substantially limits" in the…

  10. Ada as an implementation language for knowledge based systems

    NASA Technical Reports Server (NTRS)

    Rochowiak, Daniel

    1990-01-01

    Debates about the selection of programming languages often produce cultural collisions that are not easily resolved. This is especially true in the case of Ada and knowledge based programming. The construction of programming tools provides a desirable alternative for resolving the conflict.

  11. Geophysical analysis for the Ada Tepe region (Bulgaria) - case study

    NASA Astrophysics Data System (ADS)

    Trifonova, Petya; Metodiev, Metodi; Solakov, Dimcho; Simeonova, Stela; Vatseva, Rumiana

    2013-04-01

    According to the current archeological investigations Ada Tepe is the oldest gold mine in Europe with Late Bronze and Early Iron age. It is a typical low-sulfidation epithermal gold deposit and is hosted in Maastrichtian-Paleocene sedimentary rocks above a detachment fault contact with underlying Paleozoic metamorphic rocks. Ada Tepe (25o.39'E; 41o.25'N) is located in the Eastern Rhodope unit. The region is highly segmented despite the low altitude (470-750 m) due to widespread volcanic and sediment rocks susceptible to torrential erosion during the cold season. Besides the thorough geological exploration focused on identifying cost-effective stocks of mineral resources, a detailed geophysical analysis concernig diferent stages of the gold extraction project was accomplished. We present the main results from the geophysical investigation aimed to clarify the complex seismotectonic setting of the Ada Tepe site region. The overall study methodology consists of collecting, reviewing and estimating geophysical and seismological information to constrain the model used for seismic hazard assessment of the area. Geophysical information used in the present work consists of gravity, geomagnetic and seismological data. Interpretation of gravity data is applied to outline the axes of steep gravity transitions marked as potential axes of faults, flexures and other structures of dislocation. Direct inverse techniques are also utilized to estimate the form and depth of anomalous sources. For the purposes of seismological investigation of the Ada Tepe site region an earthquake catalogue is compiled for the time period 510BC - 2011AD. Statistical parameters of seismicity - annual seismic rate parameter, ?, and the b-value of the Gutenberg-Richter exponential relation for Ada Tepe site region, are estimated. All geophysical datasets and derived results are integrated using GIS techniques ensuring interoperability of data when combining, processing and visualizing obtained

  12. Measuring Ada as a software development technology in the Software Engineering Laboratory (SEL)

    NASA Technical Reports Server (NTRS)

    Agresti, W. W.

    1985-01-01

    An experiment is in progress to measure the effectiveness of Ada in the National Aeronautics and Space Administration/Goddard Space Flight Center flight dynamics software development environment. The experiment features the parallel development of software in FORTRAN and Ada. The experiment organization, objectives, and status are discussed. Experiences with an Ada training program and data from the development of a 5700-line Ada training exercise are reported.

  13. ELAPSE - NASA AMES LISP AND ADA BENCHMARK SUITE: EFFICIENCY OF LISP AND ADA PROCESSING - A SYSTEM EVALUATION

    NASA Technical Reports Server (NTRS)

    Davis, G. J.

    1994-01-01

    One area of research of the Information Sciences Division at NASA Ames Research Center is devoted to the analysis and enhancement of processors and advanced computer architectures, specifically in support of automation and robotic systems. To compare systems' abilities to efficiently process Lisp and Ada, scientists at Ames Research Center have developed a suite of non-parallel benchmarks called ELAPSE. The benchmark suite was designed to test a single computer's efficiency as well as alternate machine comparisons on Lisp, and/or Ada languages. ELAPSE tests the efficiency with which a machine can execute the various routines in each environment. The sample routines are based on numeric and symbolic manipulations and include two-dimensional fast Fourier transformations, Cholesky decomposition and substitution, Gaussian elimination, high-level data processing, and symbol-list references. Also included is a routine based on a Bayesian classification program sorting data into optimized groups. The ELAPSE benchmarks are available for any computer with a validated Ada compiler and/or Common Lisp system. Of the 18 routines that comprise ELAPSE, provided within this package are 14 developed or translated at Ames. The others are readily available through literature. The benchmark that requires the most memory is CHOLESKY.ADA. Under VAX/VMS, CHOLESKY.ADA requires 760K of main memory. ELAPSE is available on either two 5.25 inch 360K MS-DOS format diskettes (standard distribution) or a 9-track 1600 BPI ASCII CARD IMAGE format magnetic tape. The contents of the diskettes are compressed using the PKWARE archiving tools. The utility to unarchive the files, PKUNZIP.EXE, is included. The ELAPSE benchmarks were written in 1990. VAX and VMS are trademarks of Digital Equipment Corporation. MS-DOS is a registered trademark of Microsoft Corporation.

  14. Evolution of Ada technology in the flight dynamics area: Implementation/testing phase analysis

    NASA Technical Reports Server (NTRS)

    Quimby, Kelvin L.; Esker, Linda; Miller, John; Smith, Laurie; Stark, Mike; Mcgarry, Frank

    1989-01-01

    An analysis is presented of the software engineering issues related to the use of Ada for the implementation and system testing phases of four Ada projects developed in the flight dynamics area. These projects reflect an evolving understanding of more effective use of Ada features. In addition, the testing methodology used on these projects has changed substantially from that used on previous FORTRAN projects.

  15. The "Ada" Verb of Being in Bahasa Malaysia. Colorado Research in Linguistics, No. 4.

    ERIC Educational Resources Information Center

    Mader, Robin

    This paper examines the various syntactic and semantic functions of the "ada" verb of "being" in Malay. The claim is made that there is an abstract uppermost "ada" in the underlying structure of Malay sentences that asserts or denies the truth of the surface main clause. A further claim is made that the "ada" of the uppermost sentence is identical…

  16. 78 FR 10263 - Proposed Collection; Comment Request for ADA Accommodations Request Packet

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-13

    ... Internal Revenue Service Proposed Collection; Comment Request for ADA Accommodations Request Packet AGENCY... U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning the ADA Accommodations... through the Internet, at Martha.R.Brinson @irs.gov. SUPPLEMENTARY INFORMATION: Title: ADA...

  17. Evolution of Ada technology in the flight dynamics area: Design phase analysis

    NASA Technical Reports Server (NTRS)

    Quimby, Kelvin L.; Esker, Linda

    1988-01-01

    The software engineering issues related to the use of the Ada programming language during the design phase of an Ada project are analyzed. Discussion shows how an evolving understanding of these issues is reflected in the design processes of three generations of Ada projects.

  18. A graphically oriented specification language for automatic code generation. GRASP/Ada: A Graphical Representation of Algorithms, Structure, and Processes for Ada, phase 1

    NASA Technical Reports Server (NTRS)

    Cross, James H., II; Morrison, Kelly I.; May, Charles H., Jr.; Waddel, Kathryn C.

    1989-01-01

    The first phase of a three-phase effort to develop a new graphically oriented specification language which will facilitate the reverse engineering of Ada source code into graphical representations (GRs) as well as the automatic generation of Ada source code is described. A simplified view of the three phases of Graphical Representations for Algorithms, Structure, and Processes for Ada (GRASP/Ada) with respect to three basic classes of GRs is presented. Phase 1 concentrated on the derivation of an algorithmic diagram, the control structure diagram (CSD) (CRO88a) from Ada source code or Ada PDL. Phase 2 includes the generation of architectural and system level diagrams such as structure charts and data flow diagrams and should result in a requirements specification for a graphically oriented language able to support automatic code generation. Phase 3 will concentrate on the development of a prototype to demonstrate the feasibility of this new specification language.

  19. The glucokinase locus is an important contributor to glucose variation in the Chinese population at high risk for type II diabetes

    SciTech Connect

    Wu, D.A. |; Warden, C.H.; Lusis, A.J.

    1994-09-01

    Recently, major advances have been achieved in the genetics of maturity onset diabetes of the young (MODY) with two loci identified: the glucokinase (GCK) gene on chromosome (chr.) 7p and a locus near the adenosine deaminase (ADA) gene on chr. 20q. However, it is not known whether either of these MODY loci contribute to variation in glucose metabolism in populations other than MODY families. To examine this question, we have studied 94 Chinese nuclear families; 54 have both parents affected with type II diabetes, 22 have only one parent affected, and 18 have both normal parents. None of the affected diabetic probands were diagnosed prior to adulthood. Nondiabetic offspring were phenotyped by measuring plasma glucose and insulin responses to an oral glucose challenge. Parents and nondiabetic offspring were genotyped for dinucleotide repeat markers. two near the GCK locus and one near the ADA locus. Prior to linkage analysis, both glucose and insulin response variables were adjusted for the effects of age, sex, and body mass index. By non-parametric quantitative sib-pair linkage analysis, we found no evidence for linkage of glucose response variables with the ADA locus on chr. 20q (p=0.64-0.92, 146 sibpairs). However, significant evidence for linkage of log-transformed integrated glucose response area was observed with the GCK locus (haplotypes based on two tightly linked GCK markers) on chr. 7p (p=0.001, N=127). Linkage with the GCK locus was also demonstrated. In contrast, insulin variables, including integrated response area and responses at different time points, showed no evidence of linkage with either the ADA or GCK loci, despite the positive correlation between glucose and insulin responses in these families. These data raise the possibility that the GCK gene may be involved as one of the contributing genes in the etiology of type II diabetes in the Chinese population.

  20. The implementation and use of Ada on distributed systems with high reliability requirements

    NASA Technical Reports Server (NTRS)

    Knight, J. C.

    1986-01-01

    The use and implementation of Ada in distributed environments in which reliability is the primary concern were investigted. A distributed system, programmed entirely in Ada, was studied to assess the use of individual tasks without concern for the processor used. Continued development and testing of the fault tolerant Ada testbed; development of suggested changes to Ada to cope with the failures of interest; design of approaches to fault tolerant software in real time systems, and the integration of these ideas into Ada; and the preparation of various papers and presentations were discussed.

  1. Insurance benefits under the ADA: Discrimination or business as usual?

    SciTech Connect

    McFadden, M.E.

    1993-12-31

    In December 1987, John McGann discovered he had AIDS. In July 1988, his employer altered his health insurance policy by reducing lifetime coverage for AIDS to $5,000, while maintaining the million-dollar limit for all other health conditions. The United States Court of Appeals for the Fifth Circuit upheld the employer`s right to make that change. The Supreme Court denied certiori. Public outcry was immediate and voluminous. The Solicitor General argued that the new Americans with Disabilities Act would save future John McGanns from the same treatment, but the validity of this optimistic prediction is yet to be determined. The Americans with Disabilities Act of 1990 (ADA) is landmark legislation that bars discrimination against the disabled in all aspects of employment, public services, and accommodations. The Act broadly defines disability to include illnesses such as AIDS and cancer, as well as limitations on mobility, vision, and hearing. The ADA indisputably creates a private cause of action for discrimination on the basis of disability. However, depending on the standard of review chosen by the federal courts, this cause of action may or may not provide much protection to those claiming discrimination on the basis of disability in employee benefits and insurance. This article discusses the ADA`s coverage of insurance and benefits in light of the possible standards courts might use to evaluate actions of parties in suits alleging discrimination in these areas and applies those standards of review to the facts of the McGann case. 146 refs.

  2. AN ADA LINEAR ALGEBRA PACKAGE MODELED AFTER HAL/S

    NASA Technical Reports Server (NTRS)

    Klumpp, A. R.

    1994-01-01

    This package extends the Ada programming language to include linear algebra capabilities similar to those of the HAL/S programming language. The package is designed for avionics applications such as Space Station flight software. In addition to the HAL/S built-in functions, the package incorporates the quaternion functions used in the Shuttle and Galileo projects, and routines from LINPAK that solve systems of equations involving general square matrices. Language conventions in this package follow those of HAL/S to the maximum extent practical and minimize the effort required for writing new avionics software and translating existent software into Ada. Valid numeric types in this package include scalar, vector, matrix, and quaternion declarations. (Quaternions are fourcomponent vectors used in representing motion between two coordinate frames). Single precision and double precision floating point arithmetic is available in addition to the standard double precision integer manipulation. Infix operators are used instead of function calls to define dot products, cross products, quaternion products, and mixed scalar-vector, scalar-matrix, and vector-matrix products. The package contains two generic programs: one for floating point, and one for integer. The actual component type is passed as a formal parameter to the generic linear algebra package. The procedures for solving systems of linear equations defined by general matrices include GEFA, GECO, GESL, and GIDI. The HAL/S functions include ABVAL, UNIT, TRACE, DET, INVERSE, TRANSPOSE, GET, PUT, FETCH, PLACE, and IDENTITY. This package is written in Ada (Version 1.2) for batch execution and is machine independent. The linear algebra software depends on nothing outside the Ada language except for a call to a square root function for floating point scalars (such as SQRT in the DEC VAX MATHLIB library). This program was developed in 1989, and is a copyrighted work with all copyright vested in NASA.

  3. Identification of human proteins functionally conserved with the yeast putative adaptors ADA2 and GCN5.

    PubMed Central

    Candau, R; Moore, P A; Wang, L; Barlev, N; Ying, C Y; Rosen, C A; Berger, S L

    1996-01-01

    Transcriptional adaptor proteins are required for full function of higher eukaryotic acidic activators in the yeast Saccharomyces cerevisiae, suggesting that this pathway of activation is evolutionarily conserved. Consistent with this view, we have identified possible human homologs of yeast ADA2 (yADA2) and yeast GCN5 (yGCN5), components of a putative adaptor complex. While there is overall sequence similarity between the yeast and human proteins, perhaps more significant is conservation of key sequence features with other known adaptors. We show several functional similarities between the human and yeast adaptors. First, as shown for yADA2 and yGCN5, human ADA2 (hADA2) and human GCN5 (hGCN5) interacted in vivo in a yeast two-hybrid assay. Moreover, hGCN5 interacted with yADA2 in this assay, suggesting that the human proteins form similar complexes. Second, both yADA2 and hADA2 contain cryptic activation domains. Third, hGCN5 and yGCN5 had similar stabilizing effects on yADA2 in vivo. Furthermore, the region of yADA2 that interacted with yGCN5 mapped to the amino terminus of yADA2, which is highly conserved in hADA2. Most striking, is the behavior of the human proteins in human cells. First, GAL4-hADA2 activated transcription in HeLa cells, and second, either hADA2 or hGCN5 augmented GAL4-VP16 activation. These data indicated that the human proteins correspond to functional homologs of the yeast adaptors, suggesting that these cofactors play a key role in transcriptional activation. PMID:8552087

  4. NASA-evolving to Ada: Five-year plan. A plan for implementing recommendations made by the Ada and software management assessment working group

    NASA Technical Reports Server (NTRS)

    1989-01-01

    At their March 1988 meeting, members of the National Aeronautics and Space Administration (NASA) Information Resources Management (IRM) Council expressed concern that NASA may not have the infrastructure necessary to support the use of Ada for major NASA software projects. Members also observed that the agency has no coordinated strategy for applying its experiences with Ada to subsequent projects (Hinners, 27 June 1988). To deal with these problems, the IRM Council chair appointed an intercenter Ada and Software Management Assessment Working Group (ASMAWG). They prepared a report (McGarry et al., March 1989) entitled, 'Ada and Software Management in NASA: Findings and Recommendations'. That report presented a series of recommendations intended to enable NASA to develop better software at lower cost through the use of Ada and other state-of-the-art software engineering technologies. The purpose here is to describe the steps (called objectives) by which this goal may be achieved, to identify the NASA officials or organizations responsible for carrying out the steps, and to define a schedule for doing so. This document sets forth four goals: adopt agency-wide software standards and policies; use Ada as the programming language for all mission software; establish an infrastructure to support software engineering, including the use of Ada, and to leverage the agency's software experience; and build the agency's knowledge base in Ada and software engineering. A schedule for achieving the objectives and goals is given.

  5. Role of the Ada adaptor complex in gene activation by the glucocorticoid receptor.

    PubMed Central

    Henriksson, A; Almlöf, T; Ford, J; McEwan, I J; Gustafsson, J A; Wright, A P

    1997-01-01

    We have shown that the Ada adaptor complex is important for the gene activation capacity of the glucocorticoid receptor in yeast. The recently isolated human Ada2 protein also increases the potency of the receptor protein in mammalian cells. The Ada pathway is of key significance for the tau1 core transactivation domain (tau1c) of the receptor, which requires Ada for activity in vivo and in vitro. Ada2 can be precipitated from nuclear extracts by a glutathione S-transferase-tau1 fusion protein coupled to agarose beads, and a direct interaction between Ada2 and tau1c can be shown by using purified proteins. This interaction is strongly reduced by a mutation in tau1c that reduces transactivation activity. Mutations affecting the Ada complex do not reverse transcriptional squelching by the tau1 domain, as they do for the VP16 transactivation domain, and thus these powerful acidic activators differ in at least some important aspects of gene activation. Mutations that reduce the activity of the tau1c domain in wild-type yeast strains cause similar reductions in ada mutants that contain little or no Ada activity. Thus, gene activation mechanisms, in addition to the Ada pathway, are involved in the activity of the tau1c domain. PMID:9154805

  6. A genetic map of chromosome 20q12-q13. 1: Multiple highly polymorphic microsatellite and RFLP markers linked to the maturity-onset diabetes of the Young (MODY) locus

    SciTech Connect

    Rothschild, C.B.; Akots, G.; Hayworth, R.; Pettenati, M.J.; Rao, P.N.; Wood, P. ); Stolz, F.M.; Hansmann, I. ); Serino, K.; Keith, T.P. ); Fajans, S.S. )

    1993-01-01

    Multiple highly polymorphic markers have been used to construct a genetic map of the q12-q13.1 region of chromosome 20 and to map the location of the maturity-onset diabetes of the young (MODY) locus. The genetic map encompasses 23 cM and includes 11 loci with PIC values >.50, seven of which have PICs >.70. New dinucleotide repeat polymorphisms associated with the D20S17, PPGB, and ADA loci have been identified and mapped. The dinucleotide repeat polymorphisms have increased the PIC of the ADA locus to .89 and, with an additional RFLP at the D20S17 locus, the PIC of the D20S17 locus to .88. The order of the D20S17 and ADA loci determined genetically (cen-ADA-D20S17-qter) was confirmed by multicolor fluorescence in situ hybridization. The previously unmapped PPGB marker is closely linked to D20S17, with a two-point lod score of 50.53 at [cflx [theta

  7. History of the discovery of a master locus producing piRNAs: the flamenco/COM locus in Drosophila melanogaster.

    PubMed

    Goriaux, Coline; Théron, Emmanuelle; Brasset, Emilie; Vaury, Chantal

    2014-01-01

    The discovery of transposable elements (TEs) in the 1950s by B. McClintock implied the existence of cellular regulatory systems controlling TE activity. The discovery of flamenco (flam) an heterochromatic locus from Drosophila melanogaster and its ability to survey several TEs such as gypsy, ZAM, and Idefix contributed to peer deeply into the mechanisms of the genetic and epigenetic regulation of TEs. flam was the first cluster producing small RNAs to be discovered long before RNAi pathways were identified in 1998. As a result of the detailed genetic analyses performed by certain laboratories and of the sophisticated genetic tools they developed, this locus has played a major role in our understanding of piRNA mediated TE repression in animals. Here we review the first discovery of this locus and retrace decades of studies that led to our current understanding of the relationship between genomes and their TE targets. PMID:25136352

  8. History of the discovery of a master locus producing piRNAs: the flamenco/COM locus in Drosophila melanogaster

    PubMed Central

    Coline, Goriaux; Théron, Emmanuelle; Brasset, Emilie; Vaury, Chantal

    2014-01-01

    The discovery of transposable elements (TEs) in the 1950s by B. McClintock implied the existence of cellular regulatory systems controlling TE activity. The discovery of flamenco (flam) an heterochromatic locus from Drosophila melanogaster and its ability to survey several TEs such as gypsy, ZAM, and Idefix contributed to peer deeply into the mechanisms of the genetic and epigenetic regulation of TEs. flam was the first cluster producing small RNAs to be discovered long before RNAi pathways were identified in 1998. As a result of the detailed genetic analyses performed by certain laboratories and of the sophisticated genetic tools they developed, this locus has played a major role in our understanding of piRNA mediated TE repression in animals. Here we review the first discovery of this locus and retrace decades of studies that led to our current understanding of the relationship between genomes and their TE targets. PMID:25136352

  9. An approach to distributed execution of Ada programs

    NASA Technical Reports Server (NTRS)

    Volz, R. A.; Krishnan, P.; Theriault, R.

    1987-01-01

    Intelligent control of the Space Station will require the coordinated execution of computer programs across a substantial number of computing elements. It will be important to develop large subsets of these programs in the form of a single program which executes in a distributed fashion across a number of processors. A translation strategy for distributed execution of Ada programs in which library packages and subprograms may be distributed is described. A preliminary version of the translator is operational. Simple data objects (no records or arrays as yet), subprograms, and static tasks may be referenced remotely.

  10. Monogenic polyarteritis: the lesson of ADA2 deficiency.

    PubMed

    Caorsi, Roberta; Penco, Federica; Schena, Francesca; Gattorno, Marco

    2016-01-01

    The deficiency of Adenosine Deaminase 2 (DADA2) is a new autoinflammatory disease characterised by an early onset vasculopathy with livedoid skin rash associated with systemic manifestations, CNS involvement and mild immunodeficiency.This condition is secondary to autosomal recessive mutations of CECR1 (Cat Eye Syndrome Chromosome Region 1) gene, mapped to chromosome 22q11.1, that encodes for the enzymatic protein adenosine deaminase 2 (ADA2). By now 19 different mutations in CECR1 gene have been detected.The pathogenetic mechanism of DADA2 is still unclear. ADA2 in a secreted protein mainly expressed by cells of the myeloid lineage; its enzymatic activity is higher in conditions of hypoxia, inflammation and oncogenesis. Moreover ADA2 is able to induce macrophages proliferation and differentiation; it's deficiency is in fact associated with a reduction of anti-inflammatory macrophages (M2). The deficiency of ADA2 is also associated with an up-regulation of neutrophils-expressed genes and an increased secretion of pro-inflammatory cytokines. The mild immunodeficiency detected in many DADA2 patients suggests a role of this protein in the adaptive immune response; an increased mortality of B cells and a reduction in the number of memory B cells, terminally differentiated B cells and plasmacells has been described in many patients. The lack of the protein is associated with endothelium damage; however the function of this protein in the endothelial homeostasis is still unknown.From the clinical point of view, this disease is characterized by a wide spectrum of severity. Chronic or recurrent systemic inflammation with fever, elevation of acute phase reactants and skin manifestations (mainly represented by livedo reticularis) is the typical clinical picture. While in some patients the disease is mild and skin-limited, others present a severe, even lethal, disease with multi-organ involvement; the CNS involvement is rather common with ischemic or hemorrhagic strokes. In

  11. Large distributed control system using ADA in fusion research

    SciTech Connect

    Woodruff, J. P., LLNL

    1998-04-21

    Construction of the National Ignition Facility laser at Lawrence Livermore National Laboratory features a large distributed control system constructed using object-oriented software engineering techniques. Control of 60,000 devices is effected using a network of some 500 computers that run software written in Ada and communicating through CORBA. The project has completed its final design review; implementation of the first of five planned increments will be delivered at the end of fiscal year 1998. Preliminary measures of the distributed controls performance confirm the design decisions reported in this paper, and the measurement and supporting simulation of full system performance continue.

  12. An Overview of Advanced Data Acquisition System (ADAS)

    NASA Technical Reports Server (NTRS)

    Mata, Carlos T.; Steinrock, T. (Technical Monitor)

    2001-01-01

    The paper discusses the following: 1. Historical background. 2. What is ADAS? 3. R and D status. 4. Reliability/cost examples (1, 2, and 3). 5. What's new? 6. Technical advantages. 7. NASA relevance. 8. NASA plans/options. 9. Remaining R and D. 10. Applications. 11. Product benefits. 11. Commercial advantages. 12. intellectual property. Aerospace industry requires highly reliable data acquisition systems. Traditional Acquisition systems employ end-to-end hardware and software redundancy. Typically, redundancy adds weight, cost, power consumption, and complexity.

  13. Timing issues in the distributed execution of Ada programs

    NASA Technical Reports Server (NTRS)

    Volz, Richard A.; Mudge, Trevor N.

    1987-01-01

    This paper examines, in the context of distributed execution, the meaning of Ada constructs involving time. In the process, unresolved questions of interpretation and problems with the implementation of a consistent notion of time across a network are uncovered. It is observed that there are two Ada mechanisms that can involve a distributed sense of time: the conditional entry call, and the timed entry call. It is shown that a recent interpretation by the Language Maintenance Committee resolves the questions for the conditional entry calls but results in an anomaly for timed entry calls. A detailed discussion of alternative implementations for the timed entry call is made, and it is aruged that: (1) timed entry calls imply a common sense of time between the machines holding the calling and called tasks; and (2) the measurement of time for the expiration of the delay and the decision of whether or not to perform the rendezvous should be made on the machine holding the called task. The need to distinguish the unreadiness of the called task from timeouts caused by network failure is pointed out. Finally, techniques for realizing a single sense of time across the distributed system (at least to within an acceptable degree of uncertainty) are also discussed.

  14. Efficient Ada multitasking on a RISC register window architecture

    NASA Technical Reports Server (NTRS)

    Kearns, J. P.; Quammen, D.

    1987-01-01

    This work addresses the problem of reducing context switch overhead on a processor which supports a large register file - a register file much like that which is part of the Berkeley RISC processors and several other emerging architectures (which are not necessarily reduced instruction set machines in the purest sense). Such a reduction in overhead is particularly desirable in a real-time embedded application, in which task-to-task context switch overhead may result in failure to meet crucial deadlines. A storage management technique by which a context switch may be implemented as cheaply as a procedure call is presented. The essence of this technique is the avoidance of the save/restore of registers on the context switch. This is achieved through analysis of the static source text of an Ada tasking program. Information gained during that analysis directs the optimized storage management strategy for that program at run time. A formal verification of the technique in terms of an operational control model and an evaluation of the technique's performance via simulations driven by synthetic Ada program traces are presented.

  15. ART/Ada design project, phase 1. Task 2 report: Detailed design

    NASA Technical Reports Server (NTRS)

    Allen, Bradley P.

    1988-01-01

    Various issues are studied in the context of the design of an Ada based expert system building tool. Using an existing successful design as a starting point, the impact is analyzed of the Ada language and Ada development methodologies on that design, the Ada system is redesigned, and its performance is analyzed using both complexity-theoretic and empirical techniques. The algorithms specified in the overall design are refined, resolving and documenting any open design issues, identifying each system module, documenting the internal architecture and control logic, and describing the primary data structures involved in the module.

  16. Propagation of genetic variation in gene regulatory networks

    PubMed Central

    Plahte, Erik; Gjuvsland, Arne B.; Omholt, Stig W.

    2013-01-01

    A future quantitative genetics theory should link genetic variation to phenotypic variation in a causally cohesive way based on how genes actually work and interact. We provide a theoretical framework for predicting and understanding the manifestation of genetic variation in haploid and diploid regulatory networks with arbitrary feedback structures and intra-locus and inter-locus functional dependencies. Using results from network and graph theory, we define propagation functions describing how genetic variation in a locus is propagated through the network, and show how their derivatives are related to the network’s feedback structure. Similarly, feedback functions describe the effect of genotypic variation of a locus on itself, either directly or mediated by the network. A simple sign rule relates the sign of the derivative of the feedback function of any locus to the feedback loops involving that particular locus. We show that the sign of the phenotypically manifested interaction between alleles at a diploid locus is equal to the sign of the dominant feedback loop involving that particular locus, in accordance with recent results for a single locus system. Our results provide tools by which one can use observable equilibrium concentrations of gene products to disclose structural properties of the network architecture. Our work is a step towards a theory capable of explaining the pleiotropy and epistasis features of genetic variation in complex regulatory networks as functions of regulatory anatomy and functional location of the genetic variation. PMID:23997378

  17. Propagation of genetic variation in gene regulatory networks.

    PubMed

    Plahte, Erik; Gjuvsland, Arne B; Omholt, Stig W

    2013-08-01

    A future quantitative genetics theory should link genetic variation to phenotypic variation in a causally cohesive way based on how genes actually work and interact. We provide a theoretical framework for predicting and understanding the manifestation of genetic variation in haploid and diploid regulatory networks with arbitrary feedback structures and intra-locus and inter-locus functional dependencies. Using results from network and graph theory, we define propagation functions describing how genetic variation in a locus is propagated through the network, and show how their derivatives are related to the network's feedback structure. Similarly, feedback functions describe the effect of genotypic variation of a locus on itself, either directly or mediated by the network. A simple sign rule relates the sign of the derivative of the feedback function of any locus to the feedback loops involving that particular locus. We show that the sign of the phenotypically manifested interaction between alleles at a diploid locus is equal to the sign of the dominant feedback loop involving that particular locus, in accordance with recent results for a single locus system. Our results provide tools by which one can use observable equilibrium concentrations of gene products to disclose structural properties of the network architecture. Our work is a step towards a theory capable of explaining the pleiotropy and epistasis features of genetic variation in complex regulatory networks as functions of regulatory anatomy and functional location of the genetic variation.

  18. Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).

    PubMed

    Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H

    2011-03-01

    Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA.

  19. Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry.

    PubMed

    Sanchez, Juan J; Monaghan, Gemma; Børsting, Claus; Norbury, Gail; Morling, Niels; Gaspar, H Bobby

    2007-05-01

    Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb upstream of the ADA transcription start site. All patients were homozygous for the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7. Among 207 Somali immigrants to Denmark, the frequency of ADA c7C>T and the maximum likelihood estimate of the frequency of the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7 were both 0.012 (carrier frequency 2.4%). Based on the analysis of AluVpA alleles, the ADA c7C/T mutation was estimated to be approximately 7,100 years old. Approximately 1 out of 5 - 10000 Somali children will be born with ADA deficiency due to an ADA c7C/T mutation, although within certain clans the frequency may be significantly higher. ADA-SCID may be a frequent immunodeficiency disorder in Somalia, but will be underdiagnosed due to the prevailing socioeconomic and nutritional deprivation.

  20. Moving target, distributed, real-time simulation using Ada

    NASA Technical Reports Server (NTRS)

    Collins, W. R.; Feyock, S.; King, L. A.; Morell, L. J.

    1985-01-01

    Research on a precompiler solution is described for the moving target compiler problem encountered when trying to run parallel simulation algorithms on several microcomputers. The precompiler is under development at NASA-Lewis for simulating jet engines. Since the behavior of any component of a jet engine, e.g., the fan inlet, rear duct, forward sensor, etc., depends on the previous behaviors and not the current behaviors of other components, the behaviors can be modeled on different processors provided the outputs of the processors reach other processors in appropriate time intervals. The simulator works in compute and transfer modes. The Ada procedure sets for the behaviors of different components are divided up and routed by the precompiler, which essentially receives a multitasking program. The subroutines are synchronized after each computation cycle.

  1. DEC Ada interface to Screen Management Guidelines (SMG)

    NASA Technical Reports Server (NTRS)

    Laomanachareon, Somsak; Lekkos, Anthony A.

    1986-01-01

    DEC's Screen Management Guidelines are the Run-Time Library procedures that perform terminal-independent screen management functions on a VT100-class terminal. These procedures assist users in designing, composing, and keeping track of complex images on a video screen. There are three fundamental elements in the screen management model: the pasteboard, the virtual display, and the virtual keyboard. The pasteboard is like a two-dimensional area on which a user places and manipulates screen displays. The virtual display is a rectangular part of the terminal screen to which a program writes data with procedure calls. The virtual keyboard is a logical structure for input operation associated with a physical keyboard. SMG can be called by all major VAX languages. Through Ada, predefined language Pragmas are used to interface with SMG. These features and elements of SMG are briefly discussed.

  2. Rehosting and retargeting an Ada compiler: A design study

    NASA Technical Reports Server (NTRS)

    Robinson, Ray

    1986-01-01

    The goal of this study was to develop a plan for rehosting and retargeting the Air Force Armaments Lab. Ada cross compiler. This compiler was validated in Sept. 1985 using ACVC 1.6, is written in Pascal, is hosted on a CDC Cyber 170, and is targeted to an embedded Zilog Z8002. The study was performed to determine the feasibility, cost, time, and tasks required to retarget the compiler to a DEC VAX 11/78x and rehost it to an embedded U.S. Navy AN/UYK-44 computer. Major tasks identified were rehosting the compiler front end, rewriting the back end (code generator), translating the run time environment from Z8002 assembly language to AN/UYK-44 assembly language, and developing a library manager.

  3. ADASAGE4.0. Ada Application Development System

    SciTech Connect

    Taylor, M.; Russell, K.; Stewart, H.

    1990-10-01

    ADASAGE4.0 is an application development system designed to facilitate rapid and professional construction of applications written in Ada on microcomputers. Applications may vary in size from small to large multiprogram systems. ADASAGE4.0 consists of a collection of re-usable libraries for database management and form and report processing utilities having the following capabilities: basic universal type and function definitions; sequential file input/output; terminal and file input/output; DOS system command execution; data movement and fill; string manipulation; math libraries; bit manipulation; a relational database utility; data validation; menu form and window procedures; report generation; sort/merge, time, and date functions; sound production; editing; and index rebuilding. These capabilities are integrated to allow the development of an efficient system. As an application is designed and developed, ADASAGE capabilities are selected and included along with any requirements unique to that application.

  4. ADASAGE4.02-MERIDIAN. Ada Application Development System

    SciTech Connect

    Stewart, K.; Russell, K.

    1990-10-01

    ADASAGE is an application development system designed to facilitate rapid and professional construction of applications written in Ada on microcomputers. Applications may vary in size from small to large multiprogram systems. ADASAGE consists of a collection of re-usable libraries for database management and form and report processing utilities having the following capabilities: basic universal type and function definitions; sequential file input/output; terminal and file input/output; DOS system command execution; data movement and fill; string manipulation; math libraries; bit manipulation; a relational database utility; data validation; menu form and window procedures; report generation; sort/merge, time, and date functions; sound production; editing; and index rebuilding. These capabilities are integrated to allow the development of an efficient system. As an application is designed and developed, ADASAGE capabilities are selected and included along with any requirements unique to that application.

  5. ADASAGE3.1; Ada Application Development System

    SciTech Connect

    Taylor, M.; Russell, K.; Stewart, H.

    1990-10-01

    ADASAGE is an application development system designed to facilitate rapid and professional construction of applications written in Ada on microcomputers. Applications may vary in size from small to large multiprogram systems. ADASAGE consists of a collection of re-usable libraries for database management and form and report processing utilities having the following capabilities: basic universal type and function definitions; sequential file input/output; terminal and file input/output; DOS system command execution; data movement and fill; string manipulation; math libraries; bit manipulation; a relational database utility; data validation; menu form and window procedures; report generation; sort/merge, time, and date functions; sound production; editing; and index rebuilding. These capabilities are integrated to allow the development of an efficient system. As an application is designed and developed, ADASAGE capabilities are selected and included along with any requirements unique to that application.

  6. ADASAGE4.02-ALSYS. Ada Application Development System

    SciTech Connect

    Stewart, K.; Russell, K.

    1990-10-01

    ADASAGE is an application development system designed to facilitate rapid and professional construction of applications written in Ada on microcomputers. Applications may vary in size from small to large multiprogram systems. ADASAGE consists of a collection of re-usable libraries for database management and form and report processing utilities having the following capabilities: basic universal type and function definitions; sequential file input/output; terminal and file input/output; DOS system command execution; data movement and fill; string manipulation; math libraries; bit manipulation; a relational database utility; data validation; menu form and window procedures; report generation; sort/merge, time, and date functions; sound production; editing; and index rebuilding. These capabilities are integrated to allow the development of an efficient system. As an application is designed and developed, ADASAGE capabilities are selected and included along with any requirements unique to that application.

  7. School Issues Under [Section] 504 and the ADA: The Latest and Greatest.

    ERIC Educational Resources Information Center

    Aleman, Steven R.

    This paper highlights recent guidance and rulings from the Office of Civil Rights (OCR) of interest to administrators, advocates, and attorneys. It is a companion piece to Student Issues on SectionNB504/ADA: The Latest and Greatest. Compliance with SectionNB504 and the Americans with Disabilities Act (ADA) continues to involve debate and dialog on…

  8. Lessons learned in the transition to Ada from FORTRAN at NASA/Goddard

    NASA Technical Reports Server (NTRS)

    Brophy, Carolyn Elizabeth

    1989-01-01

    Two dynamics satellite simulators are developed from the same requirements, one in Ada and the other in FORTRAN. The purpose of the research was to find out how well the prescriptive Ada development model worked to develop the Ada simulator. The FORTRAN simulator development, as well as past FORTRAN developments, provided a baseline for comparison. Since this was the first simulator developed, the prescriptive Ada development model had many similarities to the usual FORTRAN development model. However, it was modified to include longer design and shorter testing phases, which is generally expected with Ada developments. One result was that the percentage of time the Ada project spent in the various development activities was very similar to the percentage of time spent in these activities when doing a FORTRAN project. Another finding was the difficulty the Ada team had with unit testing as well as with integration. It was realized that adding additional steps to the design phase, such as an abstract data type analysis, and certain guidelines to the implementation phase, such as to use primarily library units and nest sparingly, would have made development easier. These are among the recommendations made to be incorporated in a new Ada development model next time.

  9. The Labor Market Experience of Workers with Disabilities: The ADA and Beyond.

    ERIC Educational Resources Information Center

    Hotchkiss, Julie L.

    This book provides a comprehensive analysis of the recent labor market experience of American workers with disabilities and an assessment of the impact the Americans with Disabilities Act (ADA) has had on that experience. Since one intention of the ADA is to break down barriers to employment for the disabled, the analyses focus on labor demand…

  10. The G22A Polymorphism of the ADA Gene and Susceptibility to Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Hettinger, Joe A.; Liu, Xudong; Holden, Jeanette Jeltje Anne

    2008-01-01

    Inborn errors of purine metabolism have been implicated as a cause for some cases of autism. This hypothesis is supported by the finding of decreased adenosine deaminase (ADA) activity in the sera of some children with autism and reports of an association of the A allele of the ADA G22A (Asp8Asn) polymorphism in individuals with autism of…

  11. NRPA Law Review. Combat Karate Class Illustrates ADA "Direct Threat" Exception.

    ERIC Educational Resources Information Center

    Kozlowski, James C.

    2000-01-01

    Describes the Americans with Disabilities Act (ADA), which prohibits discrimination against people with disabilities, highlighting a lawsuit involving a boy with AIDS who was barred from a traditional combat-oriented martial arts school. Courts ruled that his exclusion did not violate the ADA because he posed significant health and safety risks to…

  12. The implementation and use of Ada on distributed systems with high reliability requirements

    NASA Technical Reports Server (NTRS)

    Knight, J. C.; Gregory, S. T.; Urquhart, J. I. A.

    1985-01-01

    The use and implementation of Ada in distributed environments in which reliability is the primary concern were investigated. In particular, the concept that a distributed system may be programmed entirely in Ada so that the individual tasks of the system are unconcerned with which processors they are executing on, and that failures may occur in the software or underlying hardware was examined. Progress is discussed for the following areas: continued development and testing of the fault-tolerant Ada testbed; development of suggested changes to Ada so that it might more easily cope with the failure of interest; and design of new approaches to fault-tolerant software in real-time systems, and integration of these ideas into Ada.

  13. The implementation and use of Ada on distributed systems with high reliability requirements

    NASA Technical Reports Server (NTRS)

    Knight, J. C.

    1988-01-01

    The use and implementation of Ada were investigated in distributed environments in which reliability is the primary concern. In particular, the focus was on the possibility that a distributed system may be programmed entirely in Ada so that the individual tasks of the system are unconcerned with which processors are being executed, and that failures may occur in the software and underlying hardware. A secondary interest is in the performance of Ada systems and how that performance can be gauged reliably. Primary activities included: analysis of the original approach to recovery in distributed Ada programs using the Advanced Transport Operating System (ATOPS) example; review and assessment of the original approach which was found to be capable of improvement; development of a refined approach to recovery that was applied to the ATOPS example; and design and development of a performance assessment scheme for Ada programs based on a flexible user-driven benchmarking system.

  14. The implementation and use of Ada on distributed systems with reliability requirements

    NASA Technical Reports Server (NTRS)

    Reynolds, P. F.; Knight, J. C.; Urquhart, J. I. A.

    1983-01-01

    The issues involved in the use of the programming language Ada on distributed systems are discussed. The effects of Ada programs on hardware failures such as loss of a processor are emphasized. It is shown that many Ada language elements are not well suited to this environment. Processor failure can easily lead to difficulties on those processors which remain. As an example, the calling task in a rendezvous may be suspended forever if the processor executing the serving task fails. A mechanism for detecting failure is proposed and changes to the Ada run time support system are suggested which avoid most of the difficulties. Ada program structures are defined which allow programs to reconfigure and continue to provide service following processor failure.

  15. Storage management in Ada. Three reports. Volume 1: Storage management in Ada as a risk to the development of reliable software. Volume 2: Relevant aspects of language. Volume 3: Requirements of the language versus manifestations of current implementations

    NASA Technical Reports Server (NTRS)

    Auty, David

    1988-01-01

    The risk to the development of program reliability is derived from the use of a new language and from the potential use of new storage management techniques. With Ada and associated support software, there is a lack of established guidelines and procedures, drawn from experience and common usage, which assume reliable behavior. The risk is identified and clarified. In order to provide a framework for future consideration of dynamic storage management on Ada, a description of the relevant aspects of the language is presented in two sections: Program data sources, and declaration and allocation in Ada. Storage-management characteristics of the Ada language and storage-management characteristics of Ada implementations are differentiated. Terms that are used are defined in a narrow and precise sense. The storage-management implications of the Ada language are described. The storage-management options available to the Ada implementor and the implications of the implementor's choice for the Ada programmer are also described.

  16. Research, development, training, and education using the Ada programming language. Final report, 1 September 1987-31 May 1989

    SciTech Connect

    Harrison, G.C.

    1989-07-16

    The primary goal of this activity was to conduct research in the application and development of Ada, and in broader terms the objectives were as follows: (1) To develop numerical algorithms for parallel processing using the Ada language; (2) To develop new methodologies in reusing Ada software; (3) To solve select problems in applied mathematics using MACSYMA and Ada; (4) Simulate the interactions of nodes in a network using Ada; (5) To increase the cadre of educations available to provide Ada training by conducting Ada workshops for Norfolk State University faculty and staff; (6) To develop a series of in-class and individualized modules addressing Ada programming using computer-assisted instruction; and (7) To disseminate research and computer-aided instruction modules to other minority institutions through computer networking, workshops, and lecture series.

  17. Molecular Epidemiology of sil Locus in Clinical Streptococcus pyogenes Strains

    PubMed Central

    Plainvert, Céline; Dinis, Márcia; Ravins, Miriam; Hanski, Emanuel; Touak, Gérald; Dmytruk, Nicolas; Fouet, Agnès

    2014-01-01

    Streptococcus pyogenes (group A Streptococcus [GAS]) causes a wide variety of diseases, ranging from mild noninvasive to severe invasive infections. Mutations in regulatory components have been implicated in the switch from colonization to invasive phenotypes. The inactivation of the sil locus, composed of six genes encoding a quorum-sensing complex, gives rise to a highly invasive strain. However, studies conducted on limited collections of GAS strains suggested that sil prevalence is around 15%; furthermore, whereas a correlation between the presence of sil and the genetic background was suggested, no link between the presence of a functional sil locus and the invasive status was assessed. We established a collection of 637 nonredundant strains covering all emm genotypes present in France and of known clinical history; 68%, 22%, and 10% were from invasive infections, noninvasive infections, and asymptomatic carriage, respectively. Among the 637 strains, 206 were sil positive. The prevalence of the sil locus varied according to the emm genotype, being present in >85% of the emm4, emm18, emm32, emm60, emm87, and emm90 strains and absent from all emm1, emm28, and emm89 strains. A random selection based on 2009 French epidemiological data indicated that 16% of GAS strains are sil positive. Moreover, due to mutations leading to truncated proteins, only 9% of GAS strains harbor a predicted functional sil system. No correlation was observed between the presence or absence of a functional sil locus and the strain invasiveness status. PMID:24671796

  18. 76 FR 14745 - Notice To Rescind a Notice of Intent To Prepare an Environmental Impact Statement, Ada and Canyon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-17

    ... Statement, Ada and Canyon Counties, ID AGENCY: Federal Highway Administration. ACTION: Rescind Notice of... Statement for a proposed highway project in Ada and Canyon County, Idaho is being rescinded. FOR FURTHER... Ballantyne Lane in Ada County. The project is commonly known as the State Highway 44 Corridor...

  19. Locus of control and obesity.

    PubMed

    Neymotin, Florence; Nemzer, Louis R

    2014-01-01

    In the developed world, the hazards associated with obesity have largely outstripped the risk of starvation. Obesity remains a difficult public health issue to address, due in large part to the many disciplines involved. A full understanding requires knowledge in the fields of genetics, endocrinology, psychology, sociology, economics, and public policy - among others. In this short review, which serves as an introduction to the Frontiers in Endocrinology research topic, we address one cross-disciplinary relationship: the interaction between the hunger/satiation neural circuitry, an individual's perceived locus of control, and the risk for obesity. Mammals have evolved a complex system for modulating energy intake. Overlaid on this, in humans, there exists a wide variation in "perceived locus of control" - that is, the extent to which an individual believes to be in charge of the events that affect them. Whether one has primarily an internal or external locus of control itself affects, and is affected by, external and physiological factors and has been correlated with the risk for obesity. Thus, the path from hunger and satiation to an individual's actual behavior may often be moderated by psychological factors, included among which is locus of control. PMID:25339940

  20. Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors.

    PubMed Central

    Marcus, G A; Silverman, N; Berger, S L; Horiuchi, J; Guarente, L

    1994-01-01

    A selection for yeast mutants resistant to GAL4-VP16-induced toxicity previously identified two genes, ADA2 and ADA3, which may function as adaptors for some transcriptional activation domains and thereby facilitate activation. Here we identify two new genes by the same selection, one of which is identical to GCN5. We show that gcn5 mutants share properties with ada mutants, including slow growth, temperature sensitivity and reduced activation by the VP16 and GCN4 activation domains. Double mutant studies suggest that ADA2 and GCN5 function together in a complex or pathway. Moreover, we demonstrate that GCN5 binds to ADA2 both by the two-hybrid assay in vivo and by co-immunoprecipitation in vitro. This suggests that ADA2 and GCN5 are part of a heteromeric complex that mediates transcriptional activation. Finally, we demonstrate the functional importance of the bromodomain of GCN5, a sequence found in other global transcription factors such as the SWI/SNF complex and the TATA binding protein-associated factors. This domain is not required for the interaction between GCN5 and ADA2 and thus may mediate a more general activity of transcription factors. Images PMID:7957049

  1. Development of Immunocapture-LC/MS Assay for Simultaneous ADA Isotyping and Semiquantitation

    PubMed Central

    2016-01-01

    Therapeutic proteins and peptides have potential to elicit immune responses resulting in anti-drug antibodies that can pose problems for both patient safety and product efficacy. During drug development immunogenicity is usually examined by risk-based approach along with specific strategies for developing “fit-for-purpose” bioanalytical approaches. Enzyme-linked immunosorbent assays and electrochemiluminescence immunoassays are the most widely used platform for ADA detection due to their high sensitivity and throughput. During the past decade, LC/MS has emerged as a promising technology for quantitation of biotherapeutics and protein biomarkers in biological matrices, mainly owing to its high specificity, selectivity, multiplexing, and wide dynamic range. In fully taking these advantages, we describe here an immunocapture-LC/MS methodology for simultaneous isotyping and semiquantitation of ADA in human plasma. Briefly, ADA and/or drug-ADA complex is captured by biotinylated drug or anti-drug Ab, immobilized on streptavidin magnetic beads, and separated from human plasma by a magnet. ADA is then released from the beads and subjected to trypsin digestion followed by LC/MS detection of specific universal peptides for each ADA isotype. The LC/MS data are analyzed using cut-point and calibration curve. The proof-of-concept of this methodology is demonstrated by detecting preexisting ADA in human plasma. PMID:27034966

  2. The implementation and use of Ada on distributed systems with high reliability requirements

    NASA Technical Reports Server (NTRS)

    Knight, J. C.; Reynolds, P. F.

    1982-01-01

    The use and implementation of Ada in distributed environments in which the hardware components are assumed to be unreliable is investigated. The possibility that a distributed system can be programmed entirely in Ada so that the individual tasks of the system are unconcerned with which processor they are executing on, and that failures can occur in the underlying hardware is considered. The reduced cost of computer hardware and the advantages of distributed processing (for example, increased reliability through redundancy and greater flexibility) indicate that many aerospace computer systems can be distributed. The use of Ada and distributed systems is a good combination for aerospace embedded systems.

  3. Ada compiler evaluation on the Space Station Freedom Software Support Environment project

    NASA Technical Reports Server (NTRS)

    Badal, D. L.

    1989-01-01

    This paper describes the work in progress to select the Ada compilers for the Space Station Freedom Program (SSFP) Software Support Environment (SSE) project. The purpose of the SSE Ada compiler evaluation team is to establish the criteria, test suites, and benchmarks to be used for evaluating Ada compilers for the mainframes, workstations, and the realtime target for flight- and ground-based computers. The combined efforts and cooperation of the customer, subcontractors, vendors, academia and SIGAda groups made it possible to acquire the necessary background information, benchmarks, test suites, and criteria used.

  4. AdaBoost-based algorithm for network intrusion detection.

    PubMed

    Hu, Weiming; Hu, Wei; Maybank, Steve

    2008-04-01

    Network intrusion detection aims at distinguishing the attacks on the Internet from normal use of the Internet. It is an indispensable part of the information security system. Due to the variety of network behaviors and the rapid development of attack fashions, it is necessary to develop fast machine-learning-based intrusion detection algorithms with high detection rates and low false-alarm rates. In this correspondence, we propose an intrusion detection algorithm based on the AdaBoost algorithm. In the algorithm, decision stumps are used as weak classifiers. The decision rules are provided for both categorical and continuous features. By combining the weak classifiers for continuous features and the weak classifiers for categorical features into a strong classifier, the relations between these two different types of features are handled naturally, without any forced conversions between continuous and categorical features. Adaptable initial weights and a simple strategy for avoiding overfitting are adopted to improve the performance of the algorithm. Experimental results show that our algorithm has low computational complexity and error rates, as compared with algorithms of higher computational complexity, as tested on the benchmark sample data. PMID:18348941

  5. Locus of Control and Status Attainment.

    ERIC Educational Resources Information Center

    Bensman, Miriam Roza; Haller, Archibald O.

    Utilizing data derived from 277 rural, male respondents initially enrolled in Lenawee County, Michigan high schools, the Rotter's Internal-External Locus of Control Scale was employed to test the hypothesis that locus of control will have interactive rather than additive effects on the process of status attainment. Locus of control was defined as…

  6. Four Possible Steps to Reduce Greenhouse Gas Emissions in Ada, Oklahoma

    EPA Science Inventory

    An overview of federal, state, and city initiatives on climate change are presented. Specific steps for the City of Ada, Oklahoma, are presented. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.

  7. System testing of a production Ada (trademark) project: The GRODY study

    NASA Technical Reports Server (NTRS)

    Seigle, Jeffrey; Esker, Linda; Shi, Ying-Liang

    1990-01-01

    The use of the Ada language and design methodologies that utilize its features has a strong impact on all phases of the software development project lifecycle. At the National Aeronautics and Space Administration/Goddard Space Flight Center (NASA/GSFC), the Software Engineering Laboratory (SEL) conducted an experiment in parallel development of two flight dynamics systems in FORTRAN and Ada. The teams found some qualitative differences between the system test phases of the two projects. Although planning for system testing and conducting of tests were not generally affected by the use of Ada, the solving of problems found in system testing was generally facilitated by Ada constructs and design methodology. Most problems found in system testing were not due to difficulty with the language or methodology but to lack of experience with the application.

  8. The implementation and use of Ada on distributed systems with high reliability requirements

    NASA Technical Reports Server (NTRS)

    Knight, J. C.

    1987-01-01

    Performance analysis was begin on the Ada implementations. The goal is to supply the system designer with tools that will allow a rational decision to be made about whether a particular implementation can support a given application early in the design cycle. Primary activities were: analysis of the original approach to recovery in distributed Ada programs using the Advanced Transport Operating System (ATOPS) example; review and assessment of the original approach which was found to be capable of improvement; preparation and presentation of a paper at the 1987 Washington DC Ada Symposium; development of a refined approach to recovery that is presently being applied to the ATOPS example; and design and development of a performance assessment scheme for Ada programs based on a flexible user-driven benchmarking system.

  9. Expanding ADA coverage to employee benefit plans: recent judicial and administrative developments.

    PubMed

    Mook, J R

    1995-01-01

    The Americans with Disabilities Act has been heralded as the Emancipation Proclamation for persons with disabilities. The purpose of the law is to provide nothing less than a "clear and comprehensive national mandate for the elimination of discrimination against individuals with disabilities." Precisely how the nondiscrimination principles of the ADA will be applied to an employer's provision of health benefits to its employees has been the subject of much debate since the Act's passage in 1990. Although the statutory language and the legislative history support a limited application of the ADA to benefits issues, recent court decisions and enforcement actions by the Equal Employment Opportunity Commission indicate that the ADA may have a much more profound impact in the area of benefits plan design and administration. Moreover, as benefits administrators take a much more active role in managing health care decisions, the ADA may become a vehicle for legal challenges to those decisions that affect the disabled. PMID:10172245

  10. CSF ADA Determination in Early Diagnosis of Tuberculous Meningitis in HIV-Infected Patients.

    PubMed

    Ghosh, Gopal Chandra; Sharma, Brijesh; Gupta, B B

    2016-01-01

    Tuberculous and Cryptococcal meningitis are common in HIV patients. A highly specific and sensitive rapid test for diagnosis of Tuberculous meningitis especially in setting of HIV is not available in developing countries where the burden of disease is high. We measured ADA (adenosine deaminase) levels using spectrophotometric method in the CSF of HIV patients with meningitis to differentiate Tuberculous meningitis from meningitis due to other causes. Kruskal-Wallis test was used to compare ADA values between tuberculous meningitis (TBM) and nontuberculous (non-TB) meningitis patients and a receiver-operating characteristic (ROC) analysis curve was drawn from these values. Levels of ADA in the CSF of patients with TBM were significantly higher than those in patients with meningitis due to other causes. CSF ADA level determination with a cut-off value of 6 IU/L was found to be highly specific and fairly sensitive test for the diagnosis of TBM in HIV positive patients. PMID:27144055

  11. On-line upgrade of program modules using AdaPT

    NASA Technical Reports Server (NTRS)

    Waldrop, Raymond S.; Volz, Richard A.; Smith, Gary W.; Goldsack, Stephen J.; Holzbach-Valero, A. A.

    1993-01-01

    One purpose of our research is the investigation of the effectiveness and expressiveness of AdaPT, a set of language extensions to Ada 83, for distributed systems. As a part of that effort, we are now investigating the subject of replacing, e.g. upgrading, software modules while the software system remains in operation. The AdaPT language extensions provide a good basis for this investigation for several reasons: they include the concept of specific, self-contained program modules which can be manipulated; support for program configuration is included in the language; and although the discussion will be in terms of the AdaPT language, the AdaPT to Ada 83 conversion methodology being developed as another part of this project will provide a basis for the application of our findings to Ada 83 and Ada 9X systems. The purpose of this investigation is to explore the basic mechanisms of the replacement process. With this purpose in mind, we will avoid including issues whose presence would obscure these basic mechanisms by introducing additional, unrelated concerns. Thus, while replacement in the presence of real-time deadlines, heterogeneous systems, and unreliable networks is certainly a topic of interest, we will first gain an understanding of the basic processes in the absence of such concerns. The extension of the replacement process to more complex situations can be made later. A previous report established an overview of the module replacement problem, a taxonomy of the various aspects of the replacement process, and a solution to one case in the replacement taxonomy. This report provides solutions to additional cases in the replacement process taxonomy: replacement of partitions with state and replacement of nodes. The solutions presented here establish the basic principles for module replacement. Extension of these solutions to other more complicated cases in the replacement taxonomy is direct, though requiring substantial work beyond the available funding.

  12. The implementation and use of Ada on distributed systems with high reliability requirements

    NASA Technical Reports Server (NTRS)

    Knight, J. C.; Gregory, S. T.; Urquhart, J. I. A.

    1984-01-01

    The use and implementation of Ada (a trade mark of the US Dept. of Defense) in distributed environments in which the hardware are assumed to be unreliable were investigated. The possibility that a distributed system is programmed entirely in Ada so that the individual tasks of the system are unconcerned with which processors they are executing on and failures occurring in the underlying hardware were examined.

  13. A study of the portability of an Ada system in the software engineering laboratory (SEL)

    NASA Technical Reports Server (NTRS)

    Jun, Linda O.; Valett, Susan Ray

    1990-01-01

    A particular porting effort is discussed, and various statistics on analyzing the portability of Ada and the total staff months (overall and by phase) required to accomplish the rehost, are given. This effort is compared to past experiments on the rehosting of FORTRAN systems. The discussion includes an analysis of the types of errors encountered during the rehosting, the changes required to rehost the system, experiences with the Alsys IBM Ada compiler, the impediments encountered, and the lessons learned during this study.

  14. A-D-A small molecules for solution-processed organic photovoltaic cells.

    PubMed

    Ni, Wang; Wan, Xiangjian; Li, Miaomiao; Wang, Yunchuang; Chen, Yongsheng

    2015-03-25

    A-D-A small molecules have drawn more and more attention in solution-processed organic solar cells due to the advantages of a diversity of structures, easy control of energy levels, etc. Recently, a power conversion efficiency of nearly 10% has been achieved through careful material design and device optimization. This feature article reviews recent representative progress in the design and application of A-D-A small molecules in organic photovoltaic cells.

  15. Speaking rate effects on locus equation slope.

    PubMed

    Berry, Jeff; Weismer, Gary

    2013-11-01

    A locus equation describes a 1st order regression fit to a scatter of vowel steady-state frequency values predicting vowel onset frequency values. Locus equation coefficients are often interpreted as indices of coarticulation. Speaking rate variations with a constant consonant-vowel form are thought to induce changes in the degree of coarticulation. In the current work, the hypothesis that locus slope is a transparent index of coarticulation is examined through the analysis of acoustic samples of large-scale, nearly continuous variations in speaking rate. Following the methodological conventions for locus equation derivation, data pooled across ten vowels yield locus equation slopes that are mostly consistent with the hypothesis that locus equations vary systematically with coarticulation. Comparable analyses between different four-vowel pools reveal variations in the locus slope range and changes in locus slope sensitivity to rate change. Analyses across rate but within vowels are substantially less consistent with the locus hypothesis. Taken together, these findings suggest that the practice of vowel pooling exerts a non-negligible influence on locus outcomes. Results are discussed within the context of articulatory accounts of locus equations and the effects of speaking rate change.

  16. Gene induction in response to unfolded protein in the endoplasmic reticulum is mediated through Ire1p kinase interaction with a transcriptional coactivator complex containing Ada5p

    PubMed Central

    Welihinda, Ajith A.; Tirasophon, Witoon; Green, Sarah R.; Kaufman, Randal J.

    1997-01-01

    In eukaryotic cells, accumulation of unfolded protein in the endoplasmic reticulum induces transcription of a family of genes encoding endoplasmic reticulum protein chaperones through a conserved unfolded protein response element. In Saccharomyces cerevisiae, activation of a transmembrane receptor kinase, Ire1p (Ern1p), initiates signaling, although the mediators immediately downstream of Ire1 kinase are unknown. Here we demonstrate interaction of Ire1p with the transcriptional coactivator, Gcn5p (for general control nonrepressed; also known as Ada4p). Gcn5p associates with other Ada (for alteration/deficiency in activation) gene products in a heteromeric complex and has histone acetyltransferase activity. We show that the Gcn5/Ada complex is selectively required for the unfolded protein response but not for the heat shock response. A novel mechanism is proposed in which activation of a receptor kinase recruits a transcription coactivator complex to a specific chromosomal locus to mediate localized histone acetylation, thus making specific gene sequences accessible for transcription. PMID:9113982

  17. Vector-matrix-quaternion, array and arithmetic packages: All HAL/S functions implemented in Ada

    NASA Technical Reports Server (NTRS)

    Klumpp, Allan R.; Kwong, David D.

    1986-01-01

    The HAL/S avionics programmers have enjoyed a variety of tools built into a language tailored to their special requirements. Ada is designed for a broader group of applications. Rather than providing built-in tools, Ada provides the elements with which users can build their own. Standard avionic packages remain to be developed. These must enable programmers to code in Ada as they have coded in HAL/S. The packages under development at JPL will provide all of the vector-matrix, array, and arithmetic functions described in the HAL/S manuals. In addition, the linear algebra package will provide all of the quaternion functions used in Shuttle steering and Galileo attitude control. Furthermore, using Ada's extensibility, many quaternion functions are being implemented as infix operations; equivalent capabilities were never implemented in HAL/S because doing so would entail modifying the compiler and expanding the language. With these packages, many HAL/S expressions will compile and execute in Ada, unchanged. Others can be converted simply by replacing the implicit HAL/S multiply operator with the Ada *. Errors will be trapped and identified. Input/output will be convenient and readable.

  18. Constructing a working taxonomy of functional Ada software components for real-time embedded system applications

    NASA Technical Reports Server (NTRS)

    Wallace, Robert

    1986-01-01

    A major impediment to a systematic attack on Ada software reusability is the lack of an effective taxonomy for software component functions. The scope of all possible applications of Ada software is considered too great to allow the practical development of a working taxonomy. Instead, for the purposes herein, the scope of Ada software application is limited to device and subsystem control in real-time embedded systems. A functional approach is taken in constructing the taxonomy tree for identified Ada domain. The use of modular software functions as a starting point fits well with the object oriented programming philosophy of Ada. Examples of the types of functions represented within the working taxonomy are real time kernels, interrupt service routines, synchronization and message passing, data conversion, digital filtering and signal conditioning, and device control. The constructed taxonomy is proposed as a framework from which a need analysis can be performed to reveal voids in current Ada real-time embedded programming efforts for Space Station.

  19. 6th Circuit: insurance policies are not covered by the ADA.

    PubMed

    1997-08-22

    The 6th U.S. Circuit Court of Appeals ruled that Title III of the Americans with Disabilities Act (ADA) does not cover the products that an insurer offers. The ADA only covers the physical premises of an insurance company. The court also ruled that the ADA does not mandate equality in employer-provider insurance coverage between people with varying types of disabilities. According to the court, the ADA only requires that all eligible employees be able to enroll in the plan. The case was brought by [name removed], a former employee of Schering-Plough Corporation, who complained that the long-term disability plan sponsored by the company and operated by Metropolitan Life Insurance Company, violated the ADA. The plan limited mental illness disability benefits to two years but did not place a similar cap on physical conditions. The ruling, binding in Tennessee, Kentucky, Ohio, and Michigan, contradicts earlier opinions which held that insurance products are subject to Title III of the ADA. The ruling states that Title III does not control the content of a long-term disability policy offered by an employer. Previous precedents set by the 1st Circuit Court in 1994 that had been viewed as protecting persons living with AIDS (PWAs) from discrimination in insurance programs and products were rejected by this ruling.

  20. Genomic characterization of the Atlantic cod sex-locus.

    PubMed

    Star, Bastiaan; Tørresen, Ole K; Nederbragt, Alexander J; Jakobsen, Kjetill S; Pampoulie, Christophe; Jentoft, Sissel

    2016-01-01

    A variety of sex determination mechanisms can be observed in evolutionary divergent teleosts. Sex determination is genetic in Atlantic cod (Gadus morhua), however the genomic location or size of its sex-locus is unknown. Here, we characterize the sex-locus of Atlantic cod using whole genome sequence (WGS) data of 227 wild-caught specimens. Analyzing more than 55 million polymorphic loci, we identify 166 loci that are associated with sex. These loci are located in six distinct regions on five different linkage groups (LG) in the genome. The largest of these regions, an approximately 55 Kb region on LG11, contains the majority of genotypes that segregate closely according to a XX-XY system. Genotypes in this region can be used genetically determine sex, whereas those in the other regions are inconsistently sex-linked. The identified region on LG11 and its surrounding genes have no clear sequence homology with genes or regulatory elements associated with sex-determination or differentiation in other species. The functionality of this sex-locus therefore remains unknown. The WGS strategy used here proved adequate for detecting the small regions associated with sex in this species. Our results highlight the evolutionary flexibility in genomic architecture underlying teleost sex-determination and allow practical applications to genetically sex Atlantic cod. PMID:27499266

  1. Genomic characterization of the Atlantic cod sex-locus

    PubMed Central

    Star, Bastiaan; Tørresen, Ole K.; Nederbragt, Alexander J.; Jakobsen, Kjetill S.; Pampoulie, Christophe; Jentoft, Sissel

    2016-01-01

    A variety of sex determination mechanisms can be observed in evolutionary divergent teleosts. Sex determination is genetic in Atlantic cod (Gadus morhua), however the genomic location or size of its sex-locus is unknown. Here, we characterize the sex-locus of Atlantic cod using whole genome sequence (WGS) data of 227 wild-caught specimens. Analyzing more than 55 million polymorphic loci, we identify 166 loci that are associated with sex. These loci are located in six distinct regions on five different linkage groups (LG) in the genome. The largest of these regions, an approximately 55 Kb region on LG11, contains the majority of genotypes that segregate closely according to a XX-XY system. Genotypes in this region can be used genetically determine sex, whereas those in the other regions are inconsistently sex-linked. The identified region on LG11 and its surrounding genes have no clear sequence homology with genes or regulatory elements associated with sex-determination or differentiation in other species. The functionality of this sex-locus therefore remains unknown. The WGS strategy used here proved adequate for detecting the small regions associated with sex in this species. Our results highlight the evolutionary flexibility in genomic architecture underlying teleost sex-determination and allow practical applications to genetically sex Atlantic cod. PMID:27499266

  2. Participatory Workplace Wellness Programs: Reward, Penalty, and Regulatory Conflict

    PubMed Central

    Pomeranz, Jennifer L

    2015-01-01

    Context In keeping with the Patient Protection and Affordable Care Act, Congress revised the law related to workplace wellness programs. In June 2013, the Departments of Treasury, Labor, and Health and Human Services passed the final regulations, updating their 2006 regulatory framework. Participatory programs that reward the completion of a health risk assessment are now the most common type of wellness program in the United States. However, legal and ethical concerns emerge when employers utilize incentives that raise questions about the voluntariness of such programs. At issue is that under the Americans with Disabilities Act (ADA) of 1990, employers cannot require health-related inquiries and exams. Methods To analyze the current interpretation of the ADA, I conducted research on both LexisNexis and federal agency websites. The resulting article evaluates the differences in the language of Congress's enabling legislation and the federal departments’ regulations and how they may conflict with the ADA. It also reviews the federal government's authority to address both the legal conflict and ethical concerns related to nonvoluntary participatory programs. Findings Employers’ practices and the federal departments’ regulations conflict with the current interpretation of the ADA by permitting employers to penalize employees who do not complete a health risk assessment. The departments’ regulations may be interpreted as conflicting with Congress's legislation, which mentions penalties only for health-contingent wellness programs. Furthermore, the regulatory protections for employees applicable to health-contingent wellness programs do not apply to participatory programs. Conclusions Either Congress or the federal agencies should address the conflict among employers’ practices, the wellness regulations, and the ADA and also consider additional protections for employees. Employers can avoid ethical and legal complications by offering voluntary programs with

  3. Characterization of a Multipeptide Lantibiotic Locus in Streptococcus pneumoniae

    PubMed Central

    Maricic, Natalie; Anderson, Erica S.; Opipari, AnneMarie E.; Yu, Emily A.

    2016-01-01

    ABSTRACT Bacterial communities are established through a combination of cooperative and antagonistic interactions between the inhabitants. Competitive interactions often involve the production of antimicrobial substances, including bacteriocins, which are small antimicrobial peptides that target other community members. Despite the nearly ubiquitous presence of bacteriocin-encoding loci, inhibitory activity has been attributed to only a small fraction of gene clusters. In this study, we characterized a novel locus (the pld locus) in the pathogen Streptococcus pneumoniae that drives the production of a bacteriocin called pneumolancidin, which has broad antimicrobial activity. The locus encodes an unusual tandem array of four inhibitory peptides, three of which are absolutely required for antibacterial activity. The three peptide sequences are similar but appear to play distinct roles in regulation and inhibition. A modification enzyme typically found in loci encoding a class of highly modified bacteriocins called lantibiotics was required for inhibitory activity. The production of pneumolancidin is controlled by a two-component regulatory system that is activated by the accumulation of modified peptides. The locus is located on a mobile element that has been found in many pneumococcal lineages, although not all elements carry the pld genes. Intriguingly, a minimal region containing only the genes required for pneumolancidin immunity was found in several Streptococcus mitis strains. The pneumolancidin-producing strain can inhibit nearly all pneumococci tested to date and provided a competitive advantage in vivo. These peptides not only represent a unique strategy for bacterial competition but also are an important resource to guide the development of new antimicrobials. PMID:26814178

  4. Dissection of the locus control function located on the chicken lysozyme gene domain in transgenic mice.

    PubMed Central

    Bonifer, C; Yannoutsos, N; Krüger, G; Grosveld, F; Sippel, A E

    1994-01-01

    The entire chicken lysozyme gene locus including all known cis-regulatory sequences and the 5' and 3' matrix attachment sites defining the borders of the DNase I sensitive chromatin domain, is expressed at a high level and independent of its chromosomal position in macrophages of transgenic mice. It was concluded that the lysozyme gene locus carries a locus control function. We analysed several cis-regulatory deletion mutants to investigate their influence on tissue specificity and level of expression. Position independent expression of the gene is lost whenever one of the upstream tissue specific enhancer regions is deleted, although tissue specific expression is usually retained. Deletion of the domain border fragments has no influence on copy number dependency of expression. However, without these regions an increased incidence of ectopic expression is observed. This suggests that the domain border fragments may help to suppress transgene expression in inappropriate tissues. We conclude, that position independent expression of the lysozyme gene is not controlled by a single specific region of the locus but is the result of the concerted action of several tissue specific upstream regulatory DNA elements with the promoter. Images PMID:7937146

  5. Platelet aggregation and serum adenosine deaminase (ADA) activity in pregnancy associated with diabetes, hypertension and HIV.

    PubMed

    Leal, Claudio A M; Leal, Daniela B R; Adefegha, Stephen A; Morsch, Vera M; da Silva, José E P; Rezer, João F P; Schrekker, Clarissa M L; Abdalla, Faida H; Schetinger, Maria R C

    2016-07-01

    Platelet aggregation and adenosine deaminase (ADA) activity were evaluated in pregnant women living with some disease conditions including hypertension, diabetes mellitus and human immunodeficiency virus infection. The subject population is consisted of 15 non-pregnant healthy women [control group (CG)], 15 women with normal pregnancy (NP), 7 women with hypertensive pregnancy (HP), 10 women with gestational diabetes mellitus (GDM) and 12 women with human immunodeficiency virus-infected pregnancy (HIP) groups. The aggregation of platelets was checked using an optical aggregometer, and serum ADA activity was determined using the colorimetric method. After the addition of 5 µM of agonist adenosine diphosphate, the percentage of platelet aggregation was significantly (p < 0·05) increased in NP, HP, GDM and HIP groups when compared with the CG, while the addition of 10 µM of the same agonist caused significant (p < 0·05) elevations in HP, GDM and HIP groups when compared with CG. Furthermore, ADA activity was significantly (p < 0·05) enhanced in NP, HP, GDM and HIP groups when compared with CG. In this study, the increased platelet aggregation and ADA activity in pregnancy and pregnancy-associated diseases suggest that platelet aggregation and ADA activity could serve as peripheral markers for the development of effective therapy in the maintenance of homeostasis and some inflammatory process in these pathophysiological conditions. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27273565

  6. Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells.

    PubMed

    Katz, Adam J; Tholpady, Ashok; Tholpady, Sunil S; Shang, Hulan; Ogle, Roy C

    2005-03-01

    Adult human subcutaneous adipose tissue contains cells with intriguing multilineage developmental plasticity, much like marrow-derived mesenchymal stem cells. Putative stem or progenitor cells from fat have been given many different names in the literature, reflecting an early and evolving consensus regarding their phenotypic characterization. The study reported here used microarrays to evaluate over 170 genes relating to angiogenesis and extracellular matrix in undifferentiated, early-passage human adipose-derived adherent stromal (hADAS) cells isolated from three separate donors. The hADAS populations unanimously transcribed 66% of the screened genes, and 83% were transcribed by at least two of the three populations. The most highly transcribed genes relate to functional groupings such as cell adhesion, matrix proteins, growth factors and receptors, and proteases. The transcriptome of hADAS cells demonstrated by this work reveals many similarities to published profiles of bone marrow mesenchymal stem cells (MSCs). In addition, flow analysis of over 24 hADAS cell surface proteins (n = 7 donors) both confirms and expands on the existing literature and reveals strong intergroup correlation, despite an inconsistent nomenclature and the lack of standardized protocols for cell isolation and culture. Finally, based on flow analysis and reverse transcription polymerase chain reaction studies, our results suggest that hADAS cells do not express several proteins that are implicated as markers of "stemness" in other stem cell populations, including telomerase, CD133, and the membrane transporter ABCG2.

  7. The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry.

    PubMed

    la Marca, Giancarlo; Giocaliere, Elisa; Malvagia, Sabrina; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria Luisa; Canessa, Clementina; Lippi, Francesca; Romano, Francesca; Guerrini, Renzo; Resti, Massimo; Azzari, Chiara

    2014-01-01

    Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early. The aim of this study was to set-up a robust method suitable for screening with a minimized preparation process and with inexpensive running costs, for diagnosing ADA-SCID by tandem mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn screening program. We describe a protocol revised to incorporate adenosine and 2-deoxyadenosine testing into an expanded newborn screening program. We assessed the effectiveness of this approach testing dried blood spots from 4 genetically confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values were established on 50,000 healthy newborns (deoxyadenosine <0.09μmol/L, adenosine <1.61μmol/L). We also developed a second tier test to distinguish true positives from false positives and improve the positive predictive value of an initial abnormal result. In the first 18 months, the pilot project has identified a newborn with a genetically confirmed defect in adenosine deaminase (ADA) gene. The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program.

  8. Spectrum of mutations in a cohort of UK patients with ADA deficient SCID: Segregation of genotypes with specific ethnicities.

    PubMed

    Adams, Stuart P; Wilson, Melanie; Harb, Elissar; Fairbanks, Lynette; Xu-Bayford, Jinhua; Brown, Lucie; Kearney, Laura; Madkaikar, Manisha; Bobby Gaspar, H

    2015-12-01

    Severe combined immunodeficiency (SCID) arises from a number of different genetic defects, one of the most common being mutations in the gene encoding adenosine deaminase (ADA). In the UK, ADA deficient SCID compromises approximately 20% of all known cases of SCID. We carried out a retrospective analysis of the ADA gene in 46 known ADA deficient SCID patients on whom DNA had been stored. Here, we report a high frequency of two previously reported mutations and provide a link between the mutations and patient ethnicity within our patient cohort. We also report on 9 novel mutations that have been previously unreported.

  9. An enhanced Ada run-time system for real-time embedded processors

    NASA Technical Reports Server (NTRS)

    Sims, J. T.

    1991-01-01

    An enhanced Ada run-time system has been developed to support real-time embedded processor applications. The primary focus of this development effort has been on the tasking system and the memory management facilities of the run-time system. The tasking system has been extended to support efficient and precise periodic task execution as required for control applications. Event-driven task execution providing a means of task-asynchronous control and communication among Ada tasks is supported in this system. Inter-task control is even provided among tasks distributed on separate physical processors. The memory management system has been enhanced to provide object allocation and protected access support for memory shared between disjoint processors, each of which is executing a distinct Ada program.

  10. Implementation of and Ada real-time executive: A case study

    NASA Technical Reports Server (NTRS)

    Laird, James D.; Burton, Bruce A.; Koppes, Mary R.

    1986-01-01

    Current Ada language implementations and runtime environments are immature, unproven and are a key risk area for real-time embedded computer system (ECS). A test-case environment is provided in which the concerns of the real-time, ECS community are addressed. A priority driven executive is selected to be implemented in the Ada programming language. The model selected is representative of real-time executives tailored for embedded systems used missile, spacecraft, and avionics applications. An Ada-based design methodology is utilized, and two designs are considered. The first of these designs requires the use of vendor supplied runtime and tasking support. An alternative high-level design is also considered for an implementation requiring no vendor supplied runtime or tasking support. The former approach is carried through to implementation.

  11. Diagnostic value of sputum adenosine deaminase (ADA) level in pulmonary tuberculosis

    PubMed Central

    Binesh, Fariba; Jalali, Hadi; Zare, Mohammad Reza; Behravan, Farhad; Tafti, Arefeh Dehghani; Behnaz, Fatemah; Tabatabaee, Mohammad; Shahcheraghi, Seyed Hossein

    2016-01-01

    Introduction Tuberculosis is still a considerable health problem in many countries. Rapid diagnosis of this disease is important, and adenosine deaminase (ADA) has been used as a diagnostic test. The aim of this study was to assess the diagnostic value of ADA in the sputum of patients with pulmonary tuberculosis. Methods The current study included 40 patients with pulmonary tuberculosis (culture positive, smear ±) and 42 patients with non tuberculosis pulmonary diseases (culture negative). ADA was measured on all of the samples. Results The median value of ADA in non-tuberculosis patients was 2.94 (4.2) U/L and 4.01 (6.54) U/L in tuberculosis patients, but this difference was not statistically significant (p=0.100). The cut-off point of 3.1 U/L had a sensitivity of 61% and a specificity of 53%, the cut-off point of 2.81 U/L had a sensitivity of 64% and a specificity of 50% and the cut-off point of 2.78 U/L had a sensitivity of 65% and a specificity of 48%. The positive predictive values for cut-off points of 3.1, 2.81 and 2.78 U/L were 55.7%, 57.44% and 69.23%, respectively. The negative predictive values for the abovementioned cut-off points were 56.75%, 57.14% and 55.88%, respectively. Conclusion Our results showed that sputum ADA test is neither specific nor sensitive. Because of its low sensitivity and specificity, determination of sputum ADA for the diagnosis of pulmonary tuberculosis is not recommended. PMID:27482515

  12. Factors Determining Adolescent Locus of Control.

    ERIC Educational Resources Information Center

    Kopera-Frye, Karen F.; And Others

    Previous research has demonstrated an association between locus of control in adolescence and a successful transition to adulthood. Having an external locus of control has been implicated as an important factor in adolescent behaviors such as teenage pregnancy and delinquency, and has been found to be negatively related to school achievement. This…

  13. Genetic characterization and regulation of the nadB locus of Salmonella typhimurium.

    PubMed Central

    Cookson, B T; Olivera, B M; Roth, J R

    1987-01-01

    The nadB locus encodes the first enzyme of NAD synthesis. It has been reported that this gene and nadA are regulated by a positive regulatory protein encoded in the nadB region. In pursuing this regulatory mechanism, we constructed a fine-structure genetic map of the nadB gene. The region appears to include a single complementation group; no evidence for a positive regulatory element was found. Several mutations causing resistance to the analog 6-aminonicotinamide mapped within the structural gene and probably cause resistance to feedback inhibition. Regulatory mutations for nadB were isolated. These mutants mapped far from nadB near the pnuA gene, which encodes a function required for nicotinamide mononucleotide transport. The regulatory mutations appear to affect a distinct function encoded in the same operon as pnuA. PMID:3305482

  14. An Ada implementation of the network manager for the advanced information processing system

    NASA Technical Reports Server (NTRS)

    Nagle, Gail A.

    1986-01-01

    From an implementation standpoint, the Ada language provided many features which facilitated the data and procedure abstraction process. The language supported a design which was dynamically flexible (despite strong typing), modular, and self-documenting. Adequate training of programmers requires access to an efficient compiler which supports full Ada. When the performance issues for real time processing are finally addressed by more stringent requirements for tasking features and the development of efficient run-time environments for embedded systems, the full power of the language will be realized.

  15. The Spectrum Sensing Algorithm Based AdaBoost in Cognitive Radio

    NASA Astrophysics Data System (ADS)

    Tian, Deyong; Wang, Xin

    To solve the low detection rate of the primary user in the cognitive radio environment, we propose a spectrum sensing method based on AdaBoost in the case of low SNR. In this paper, a set of received signal spectrum features are first calculated and extracted the discriminant feature vector as training samples and testing samples for classification. Finally, we utilize the trained AdaBoost to detect the primary user. Test result shows that the proposed algorithm is not affected by uncertainty factors of noise and has high performance to classification detection compared with ANN, SVM and maximum-minimum eigenvalue (MME).

  16. The role of transcriptional coactivator ADA2b in Arabidopsis abiotic stress responses

    PubMed Central

    Kaldis, Athanasios; Nikoloudi, Adriana; Tsementzi, Despoina

    2011-01-01

    Plant growth and crop production can be greatly affected by common environmental stresses such as drought, high salinity and low temperatures. Gene expression is affected by several abiotic stresses. Stress-inducible genes are regulated by transcription factors and epigenetic mechanisms such as histone modifications. In this mini-review, we have explored the role of transcriptional adaptor ADA2b in Arabidopsis responses to abiotic stress. ADA2b is required for the expression of genes involved in abiotic stress either by controlling H3 and H4 acetylation in the case of salt stress or affecting nucleosome occupancy in low temperatures response. PMID:21897124

  17. The role of transcriptional coactivator ADA2b in Arabidopsis abiotic stress responses.

    PubMed

    Vlachonasios, Konstantinos E; Kaldis, Athanasios; Nikoloudi, Adriana; Tsementzi, Despoina

    2011-10-01

    Plant growth and crop production can be greatly affected by common environmental stresses such as drought, high salinity and low temperatures. Gene expression is affected by several abiotic stresses. Stress-inducible genes are regulated by transcription factors and epigenetic mechanisms such as histone modifications. In this Mini-Review, we have explored the role of transcriptional adaptor ADA2b in Arabidopsis responses to abiotic stress. ADA2b is required for the expression of genes involved in abiotic stress either by controlling H3 and H4 acetylation in the case of salt stress or affecting nucleosome occupancy in low temperatures response.

  18. Polyethylene Glycol-Conjugated Adenosine Deaminase (ADA) Therapy Provides Temporary Immune Reconstitution to a Child with Delayed-Onset ADA Deficiency

    PubMed Central

    Lainka, Elke; Hershfield, Michael S.; Santisteban, Ines; Bali, Pawan; Seibt, Annette; Neubert, Jennifer; Friedrich, Wilhelm; Niehues, Tim

    2005-01-01

    We describe the effects of polyethylene glycol-conjugated adenosine deaminase (ADA) replacement therapy on lymphocyte counts, activation, apoptosis, proliferation, and cytokine secretion in a 14-month-old girl with “delayed-onset” ADA deficiency and marked immunodysregulation. Pretreatment lymphopenia affected T cells (CD4, 150/μl; CD8, 459/μl), B cells (16/μl), and NK cells (55/μl). T cells were uniformly activated and largely apoptotic (CD4, 59%; CD8, 82%); and T-cell-dependent cytokine levels in plasma were elevated, including the levels of interleukin 2 (IL-2; 26 pg/ml), IL-4 (81 pg/ml), IL-5 (46 pg/ml), gamma interferon (1,430 pg/ml), tumor necrosis factor alpha (210 pg/ml), and IL-10 (168 pg/ml). Mitogen-stimulated peripheral blood mononuclear cells show reduced IL-2 secretion and proliferation. During the first 5 months of therapy there was clinical improvement and partial immune reconstitution, with nearly normal lymphocyte subset numbers, reduced T-cell activation and CD4-cell apoptosis, and decreased plasma cytokine levels. In parallel, IL-2 secretion and the lymphocyte mitogenic response improved. Between 4 and 7 months, immunoglobulin G antibodies to bovine ADA developed and resulted in the complete reversal of immune recovery. PMID:16002636

  19. 28 CFR Appendix B to Part 36 - Analysis and Commentary on the 2010 ADA Standards for Accessible Design

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... final rules for title II (28 CFR part 35) and title III (28 CFR part 36) of the Americans with... the Department's revised ADA title II regulation, 28 CFR 35.104 Definitions, the Department defines... consist of the 2004 ADA Accessibility Guidelines (ADAAG) and the requirements contained in 28 CFR...

  20. 28 CFR Appendix B to Part 36 - Analysis and Commentary on the 2010 ADA Standards for Accessible Design

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... final rules for title II (28 CFR part 35) and title III (28 CFR part 36) of the Americans with... the Department's revised ADA title II regulation, 28 CFR 35.104 Definitions, the Department defines... consist of the 2004 ADA Accessibility Guidelines (ADAAG) and the requirements contained in 28 CFR...

  1. 28 CFR Appendix B to Part 36 - Analysis and Commentary on the 2010 ADA Standards for Accessible Design

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... final rules for title II (28 CFR part 35) and title III (28 CFR part 36) of the Americans with... the Department's revised ADA title II regulation, 28 CFR 35.104 Definitions, the Department defines... consist of the 2004 ADA Accessibility Guidelines (ADAAG) and the requirements contained in 28 CFR...

  2. 28 CFR Appendix B to Part 36 - Analysis and Commentary on the 2010 ADA Standards for Accessible Design

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... final rules for title II (28 CFR part 35) and title III (28 CFR part 36) of the Americans with... the Department's revised ADA title II regulation, 28 CFR 35.104 Definitions, the Department defines... consist of the 2004 ADA Accessibility Guidelines (ADAAG) and the requirements contained in 28 CFR...

  3. Run-time implementation issues for real-time embedded Ada

    NASA Technical Reports Server (NTRS)

    Maule, Ruth A.

    1986-01-01

    A motivating factor in the development of Ada as the department of defense standard language was the high cost of embedded system software development. It was with embedded system requirements in mind that many of the features of the language were incorporated. Yet it is the designers of embedded systems that seem to comprise the majority of the Ada community dissatisfied with the language. There are a variety of reasons for this dissatisfaction, but many seem to be related in some way to the Ada run-time support system. Some of the areas in which the inconsistencies were found to have the greatest impact on performance from the standpoint of real-time systems are presented. In particular, a large part of the duties of the tasking supervisor are subject to the design decisions of the implementer. These include scheduling, rendezvous, delay processing, and task activation and termination. Some of the more general issues presented include time and space efficiencies, generic expansions, memory management, pragmas, and tracing features. As validated compilers become available for bare computer targets, it is important for a designer to be aware that, at least for many real-time issues, all validated Ada compilers are not created equal.

  4. Implementation of Ada protocols on Mil-STD-1553 B data bus

    NASA Technical Reports Server (NTRS)

    Ruhman, Smil; Rosemberg, Flavia

    1986-01-01

    Standardization activity of data communication in avionic systems started in 1968 for the purpose of total system integration and the elimination of heavy wire bundles carrying signals between various subassemblies. The growing complexity of avionic systems is straining the capabilities of MIL-STD-1553 B (first issued in 1973), but a much greater challenge to it is posed by Ada, the standard language adopted for real-time, computer embedded-systems. Hardware implementation of Ada communication protocols in a contention/token bus or token ring network is proposed. However, during the transition period when the current command/response multiplex data bus is still flourishing and the development environment for distributed multi-computer Ada systems is as yet lacking, a temporary accomodation of the standard language with the standard bus could be very useful and even highly desirable. By concentrating all status informtion and decisions at the bus controller, it was found to be possible to construct an elegant and efficient harware impelementation of the Ada protocols at the bus interface. This solution is discussed.

  5. 77 FR 36231 - Americans With Disabilities Act (ADA) and Architectural Barriers Act (ABA) Accessibility...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-18

    ...The Architectural and Transportation Barriers Compliance Board (Access Board) proposes to amend the Americans with Disabilities Act (ADA) and Architectural Barriers Act (ABA) Accessibility Guidelines to specifically address emergency transportable housing units that are provided by the Federal Emergency Management Agency or other entities on a temporary site in response to an emergency need......

  6. 76 FR 38124 - Applications for New Awards; Americans With Disabilities Act (ADA) National Network Regional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ... and Centers Program, published in the Federal Register on April 28, 2006 (71 FR 25472). The priorities... 350. (c) The notice of final priorities published in the Federal Register on April 28, 2006 (71 FR... Applications for New Awards; Americans With Disabilities Act (ADA) National Network Regional Centers and...

  7. EVALUATION OF THE ADA TECHNOLOGIES' ELECTRO-DECON PROCESS TO REMOVE RADIOLOGICAL CONTAMINATION

    SciTech Connect

    Pao, Jenn-Hai; Demmer, Rick L.; Argyle, Mark D.; Veatch, Brad D.

    2003-02-27

    A surface decontamination system featuring the use of ADA's electrochemical process was tested and evaluated. The process can be flexibly deployed by using an electrolyte delivery system that has been demonstrated to be reliable and effective. Experimental results demonstrate the effectiveness of this system for the surface decontamination of radiologically contaminated stainless steel.

  8. 76 FR 57013 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-15

    ... proposed modifications of its recordkeeping and reporting provisions under title VII, the ADA, and GINA. (76 FR 31892, June 2, 2011). No requests to present oral testimony at a hearing concerning the... COMMISSION 29 CFR Part 1602 RIN 3046-AA89 Recordkeeping and Reporting Requirements Under Title VII, the...

  9. 76 FR 79065 - Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ... Employment Opportunity Commission 29 CFR Part 1602 Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA CFR Correction In Title 29 of the Code of Federal Regulations, Parts 900 to 1899, revised as of July 1, 2011, in Part 1602, remove the words ``section 709(c) of title VII or section 107...

  10. Health Care and ADA Language Education Programs. Cooperative Demonstration Program: High Technology. Final Performance Report.

    ERIC Educational Resources Information Center

    Marion County Schools, Fairmont, WV.

    A project implemented cooperative training programs in the three occupational areas: ADA computer language use; respiratory therapy technician; and hospital pharmacy technician. The project's purpose was to demonstrate high technology training programs for adults as a cooperative effort among the West Virginia Department of Education, local…

  11. 75 FR 43747 - Americans With Disabilities Act (ADA) Accessibility Guidelines for Transportation Vehicles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ...., buses characterized by an elevated passenger deck located over a baggage compartment). 56 FR 45530, September 6, 1991; 63 FR 51694, September 28, 1998. The Access Board's transportation vehicle guidelines are... transportation provisions of the ADA in 1991. 56 FR 45621 and 45756, September 6, 1991. The Department...

  12. 76 FR 38129 - Applications for New Awards; Americans With Disabilities Act (ADA) National Network Knowledge...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ... Applications for New Awards; Americans With Disabilities Act (ADA) National Network Knowledge Translation... applications for new awards for fiscal year (FY) 2011. Catalog of Federal Domestic Assistance (CFDA) Number: 84.133A-7. Dates: Applications Available: June 29, 2011. Date of Pre-Application Meeting: July 20,...

  13. 75 FR 45661 - Notice of Permanent Closure on Public Lands in Ada County, ID

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... Bureau of Land Management Notice of Permanent Closure on Public Lands in Ada County, ID AGENCY: Bureau of Land Management, Interior. ACTION: Notice of permanent closure. SUMMARY: On April 12, 2010, Higby Cave and all public lands within 1,000 feet of the entrance were permanently closed to vehicle access...

  14. Determining the bistability parameter ranges of artificially induced lac operon using the root locus method.

    PubMed

    Avcu, N; Alyürük, H; Demir, G K; Pekergin, F; Cavas, L; Güzeliş, C

    2015-06-01

    This paper employs the root locus method to conduct a detailed investigation of the parameter regions that ensure bistability in a well-studied gene regulatory network namely, lac operon of Escherichia coli (E. coli). In contrast to previous works, the parametric bistability conditions observed in this study constitute a complete set of necessary and sufficient conditions. These conditions were derived by applying the root locus method to the polynomial equilibrium equation of the lac operon model to determine the parameter values yielding the multiple real roots necessary for bistability. The lac operon model used was defined as an ordinary differential equation system in a state equation form with a rational right hand side, and it was compatible with the Hill and Michaelis-Menten approaches of enzyme kinetics used to describe biochemical reactions that govern lactose metabolism. The developed root locus method can be used to study the steady-state behavior of any type of convergent biological system model based on mass action kinetics. This method provides a solution to the problem of analyzing gene regulatory networks under parameter uncertainties because the root locus method considers the model parameters as variable, rather than fixed. The obtained bistability ranges for the lac operon model parameters have the potential to elucidate the appearance of bistability for E. coli cells in in vivo experiments, and they could also be used to design robust hysteretic switches in synthetic biology. PMID:25864166

  15. Structure of the MHC A and B locus promoters in hominoids

    SciTech Connect

    Vallejo, A.N.; Pease, L.R.

    1995-04-15

    The expansion and contraction of mammalian class I multigene families raises the issue as to what determines the loss or retention of family members. We propose that accumulating changes in regulatory regions result in the loss of expression of the gene products during times critical to selection, leading to the extinction of misregulated genes. The structures of promoter regions of MHC class I genes in nonhuman primates support this view. The B promoters are more homogeneous and contain regulatory elements also found in the promoters of the homologous class I genes of more distant mammals, whereas the A locus promoters were significantly more heterogeneous, have fewer sequence motifs related to known transcription factor-binding sites and have accumulated nucleotide substitutions within one of the widely conserved class I promoter elements. These findings are consistent with the view that the more polymorphic B locus is the principal MHC locus encoding functional class I Ag-presenting molecules whereas the less polymorphic A locus is assuming a secondary role as a consequence of promoter defects. 50 refs., 5 figs., 2 tabs.

  16. A comprehensive analysis of the chorion locus in silkmoth

    PubMed Central

    Chen, Zhiwei; Nohata, Junko; Guo, Huizhen; Li, Shenglong; Liu, Jianqiu; Guo, Youbing; Yamamoto, Kimiko; Kadono-Okuda, Keiko; Liu, Chun; Arunkumar, Kallare P.; Nagaraju, Javaregowda; Zhang, Yan; Liu, Shiping; Labropoulou, Vassiliki; Swevers, Luc; Tsitoura, Panagiota; Iatrou, Kostas; Gopinathan, Karumathil P.; Goldsmith, Marian R.; Xia, Qingyou; Mita, Kazuei

    2015-01-01

    Despite more than 40 years of intense study, essential features of the silkmoth chorion (eggshell) are still not fully understood. To determine the precise structure of the chorion locus, we performed extensive EST analysis, constructed a bacterial artificial chromosome (BAC) contig, and obtained a continuous genomic sequence of 871,711 base pairs. We annotated 127 chorion genes in two segments interrupted by a 164 kb region with 5 non-chorion genes, orthologs of which were on chorion bearing scaffolds in 4 ditrysian families. Detailed transcriptome analysis revealed expression throughout choriogenesis of most chorion genes originally categorized as “middle”, and evidence for diverse regulatory mechanisms including cis-elements, alternative splicing and promoter utilization, and antisense RNA. Phylogenetic analysis revealed multigene family associations and faster evolution of early chorion genes and transcriptionally active pseudogenes. Proteomics analysis identified 99 chorion proteins in the eggshell and micropyle localization of 1 early and 6 Hc chorion proteins. PMID:26553298

  17. A comprehensive analysis of the chorion locus in silkmoth.

    PubMed

    Chen, Zhiwei; Nohata, Junko; Guo, Huizhen; Li, Shenglong; Liu, Jianqiu; Guo, Youbing; Yamamoto, Kimiko; Kadono-Okuda, Keiko; Liu, Chun; Arunkumar, Kallare P; Nagaraju, Javaregowda; Zhang, Yan; Liu, Shiping; Labropoulou, Vassiliki; Swevers, Luc; Tsitoura, Panagiota; Iatrou, Kostas; Gopinathan, Karumathil P; Goldsmith, Marian R; Xia, Qingyou; Mita, Kazuei

    2015-01-01

    Despite more than 40 years of intense study, essential features of the silkmoth chorion (eggshell) are still not fully understood. To determine the precise structure of the chorion locus, we performed extensive EST analysis, constructed a bacterial artificial chromosome (BAC) contig, and obtained a continuous genomic sequence of 871,711 base pairs. We annotated 127 chorion genes in two segments interrupted by a 164 kb region with 5 non-chorion genes, orthologs of which were on chorion bearing scaffolds in 4 ditrysian families. Detailed transcriptome analysis revealed expression throughout choriogenesis of most chorion genes originally categorized as "middle", and evidence for diverse regulatory mechanisms including cis-elements, alternative splicing and promoter utilization, and antisense RNA. Phylogenetic analysis revealed multigene family associations and faster evolution of early chorion genes and transcriptionally active pseudogenes. Proteomics analysis identified 99 chorion proteins in the eggshell and micropyle localization of 1 early and 6 Hc chorion proteins. PMID:26553298

  18. Tale of a multifaceted co-activator, hADA3: from embryogenesis to cancer and beyond.

    PubMed

    Chand, Vaibhav; Nandi, Deeptashree; Mangla, Anita Garg; Sharma, Puneet; Nag, Alo

    2016-09-01

    Human ADA3, the evolutionarily conserved transcriptional co-activator, remains the unified part of multiple cellular functions, including regulation of nuclear receptor functions, cell proliferation, apoptosis, senescence, chromatin remodelling, genomic stability and chromosomal maintenance. The past decade has witnessed exciting findings leading to considerable expansion in research related to the biology and regulation of hADA3. Embryonic lethality in homozygous knockout Ada3 mouse signifies the importance of this gene product during early embryonic development. Moreover, the fact that it is a novel target of Human Papillomavirus E6 oncoprotein, one of the most prevalent causal agents behind cervical cancer, helps highlight some of the crucial aspects of HPV-mediated oncogenesis. These findings imply the central involvement of hADA3 in regulation of various cellular functional losses accountable for the genesis of malignancy and viral infections. Recent reports also provide evidence for post-translational modifications of hADA3 leading to its instability and contributing to the malignant phenotype of cervical cancer cells. Furthermore, its association with poor prognosis of breast cancer suggests intimate association in the pathogenesis of the disease. Here, we present the first review on hADA3 with a comprehensive outlook on the molecular and functional roles of hADA3 to provoke further interest for more elegant and intensive studies exploring assorted aspects of this protein. PMID:27605378

  19. Lessons learned in the transition to ADA from FORTRAN at NASA/Goddard. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Brophy, Carolyn Elizabeth

    1989-01-01

    A case study was done at Goddard Space Flight Center, in which two dynamics satellite simulators are developed from the same requirements, one in Ada and the other in FORTRAN. The purpose of the research was to find out how well the prescriptive Ada development model worked to develop the Ada simulator. The FORTRAN simulator development, as well as past FORTRAN developments, provided a baseline for comparison. Since this was the first simulator developed here, the prescriptive Ada development model had many similarities to the usual FORTRAN development model. However, it was modified to include longer design and shorter testing phases, which is generally expected with Ada development. One surprising result was that the percentage of time the Ada project spent in the various development activities was very similar to the percentage of time spent in these activities when doing a FORTRAN project. Another surprising finding was the difficulty the Ada team had with unit testing as well as with integration. In retrospect it is realized that adding additional steps to the design phase, such as an abstract data type analysis, and certain guidelines to the implementation phase, such as to use primarily library units and nest sparingly, would have made development much easier.

  20. Tale of a multifaceted co-activator, hADA3: from embryogenesis to cancer and beyond

    PubMed Central

    Chand, Vaibhav; Nandi, Deeptashree; Mangla, Anita Garg; Sharma, Puneet

    2016-01-01

    Human ADA3, the evolutionarily conserved transcriptional co-activator, remains the unified part of multiple cellular functions, including regulation of nuclear receptor functions, cell proliferation, apoptosis, senescence, chromatin remodelling, genomic stability and chromosomal maintenance. The past decade has witnessed exciting findings leading to considerable expansion in research related to the biology and regulation of hADA3. Embryonic lethality in homozygous knockout Ada3 mouse signifies the importance of this gene product during early embryonic development. Moreover, the fact that it is a novel target of Human Papillomavirus E6 oncoprotein, one of the most prevalent causal agents behind cervical cancer, helps highlight some of the crucial aspects of HPV-mediated oncogenesis. These findings imply the central involvement of hADA3 in regulation of various cellular functional losses accountable for the genesis of malignancy and viral infections. Recent reports also provide evidence for post-translational modifications of hADA3 leading to its instability and contributing to the malignant phenotype of cervical cancer cells. Furthermore, its association with poor prognosis of breast cancer suggests intimate association in the pathogenesis of the disease. Here, we present the first review on hADA3 with a comprehensive outlook on the molecular and functional roles of hADA3 to provoke further interest for more elegant and intensive studies exploring assorted aspects of this protein. PMID:27605378

  1. Digital data sets that describe aquifer characteristics of the Vamoosa-Ada aquifer in east-central Oklahoma

    USGS Publications Warehouse

    Abbott, Marvin M.; Runkle, D.L.; Rea, Alan

    1997-01-01

    Nonproprietary format files This diskette contains digitized aquifer boundaries and maps of hydraulic conductivity, recharge, and ground-water level elevation contours for the Vamoosa-Ada aquifer in east-central Oklahoma. The Vamoosa-Ada aquifer is an important source of water that underlies about 2,320-square miles of parts of Osage, Pawnee, Payne, Creek, Lincoln, Okfuskee, and Seminole Counties. Approximately 75 percent of the water withdrawn from the Vamoosa-Ada aquifer is for municipal use. Rural domestic use and water for stock animals account for most of the remaining water withdrawn. The Vamoosa-Ada aquifer is defined in a ground-water report as consisting principally of the rocks of the Late Pennsylvanian-age Vamoosa Formation and overlying Ada Group. The Vamoosa-Ada aquifer consists of a complex sequence of fine- to very fine-grained sandstone, siltstone, shale, and conglomerate interbedded with very thin limestones. The water-yielding capabilities of the aquifer are generally controlled by lateral and vertical distribution of the sandstone beds and their physical characteristics. The Vamoosa-Ada aquifer is unconfined where it outcrops in about an 1,700-square-mile area. Most of the lines in the aquifer boundary, hydraulic conductivity, and recharge data sets were extracted from published digital surficial geology data sets based on a scale of 1:250,000, and represent geologic contacts. Some of lines in the data sets were interpolated in areas where the Vamoosa-Ada aquifer is overlain by alluvial and terrace deposits near streams and rivers. These data sets include only the outcrop area of the Vamoosa-Ada aquifer and where the aquifer is overlain by alluvial and terrace deposits. The hydraulic conductivity value and recharge rate are from a ground-water report about the Vamoosa-Ada aquifer. The water-level elevation contours were digitized from a mylar map, at a scale of 1:250,000, used to publish a plate in a ground-water report about the Vamoosa-Ada

  2. Homozygosity for a novel adenosine deaminase (ADA) nonsense mutation (Q3>X) in a child with severe combined immunodeficiency (SCID)

    SciTech Connect

    Santisteban, I.; Arrendondo-Vega, F.X.; Kelly, S. |

    1994-09-01

    A Somali girl was diagnosed with ADA-deficient SCID at 7 mo; she responded well to PEG-ADA replacement and is now 3.3 yr old. ADA mRNA was undetectable (Northern) in her cultured T cells, but was present in T cells of her parents and two sibs. All PCR-amplified exon 1 genomic clones from the patient had a C>T transition at bp 7 relative to the start of translation, replacing Gln at codon 3 (AGA) with a termination codon (TGA, Q3>X). Patient cDNA (prepared by RT-PCR with a 5{prime} primer that covered codons 1-7) had a previously described polymorphism, K80>R, but was otherwise normal, indicating that no other coding mutations were present. A predicted new genomic BfaI restriction site was used to establish her homozygosity for Q3>X and to analyze genotypes of family members. We also analyzed the segregation of a variable Alu polyA-associated TAAA repeat (AluVpA) situated 5{prime} of the ADA gene. Three different AluVpA alleles were found, one of which was only present in the father and was not associated with his Q3>X allele. Because the father`s RBCs had only {approximately}15% of normal ADA activity, we analyzed his ADA cDNA. We found a G>A transition at bp 425 that substitutes Gln for Arg142, a solvent-accessible residue, and eliminates a BsmAI site in exon 5. ADA activity of the R142>Q in vitro translation product was 20-25% of wild type ADA translation product, suggesting that R142>Q is a new {open_quote}partial{close_quote} ADA deficiency mutation. As expected, Q3>X mRNA did not yield a detectable in vitro translation product. We conclude that the patient`s father is a compound heterozygote carrying the ADA Q3>X/R142>Q genotype. {open_quote}Partial{close_quote} ADA deficiency unassociated with immunodeficiency is relatively common in individuals of African descent. The present findings and previous observations suggest that {open_quote}partial{close_quote} ADA deficiency may have had an evolutionary advantage.

  3. CCCTC-binding factor (CTCF) and cohesin influence the genomic architecture of the Igh locus and antisense transcription in pro-B cells.

    PubMed

    Degner, Stephanie C; Verma-Gaur, Jiyoti; Wong, Timothy P; Bossen, Claudia; Iverson, G Michael; Torkamani, Ali; Vettermann, Christian; Lin, Yin C; Ju, Zhongliang; Schulz, Danae; Murre, Caroline S; Birshtein, Barbara K; Schork, Nicholas J; Schlissel, Mark S; Riblet, Roy; Murre, Cornelis; Feeney, Ann J

    2011-06-01

    Compaction and looping of the ~2.5-Mb Igh locus during V(D)J rearrangement is essential to allow all V(H) genes to be brought in proximity with D(H)-J(H) segments to create a diverse antibody repertoire, but the proteins directly responsible for this are unknown. Because CCCTC-binding factor (CTCF) has been demonstrated to be involved in long-range chromosomal interactions, we hypothesized that CTCF may promote the contraction of the Igh locus. ChIP sequencing was performed on pro-B cells, revealing colocalization of CTCF and Rad21 binding at ~60 sites throughout the V(H) region and 2 other sites within the Igh locus. These numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement. To test whether CTCF was involved in locus compaction, we used 3D-FISH to measure compaction in pro-B cells transduced with CTCF shRNA retroviruses. Reduction of CTCF binding resulted in a decrease in Igh locus compaction. Long-range interactions within the Igh locus were measured with the chromosomal conformation capture assay, revealing direct interactions between CTCF sites 5' of DFL16 and the 3' regulatory region, and also the intronic enhancer (Eμ), creating a D(H)-J(H)-Eμ-C(H) domain. Knockdown of CTCF also resulted in the increase of antisense transcription throughout the D(H) region and parts of the V(H) locus, suggesting a widespread regulatory role for CTCF. Together, our findings demonstrate that CTCF plays an important role in the 3D structure of the Igh locus and in the regulation of antisense germline transcription and that it contributes to the compaction of the Igh locus. PMID:21606361

  4. The implementation and use of Ada on distributed systems with high reliability requirements

    NASA Technical Reports Server (NTRS)

    Knight, J. C.

    1986-01-01

    The general inadequacy of Ada for programming systems that must survive processor loss was shown. A solution to the problem was proposed in which there are no syntatic changes to Ada. The approach was evaluated using a full-scale, realistic application. The application used was the Advanced Transport Operating System (ATOPS), an experimental computer control system developed for a modified Boeing 737 aircraft. The ATOPS system is a full authority, real-time avionics system providing a large variety of advanced features. Methods of building fault tolerance into concurrent systems were explored. A set of criteria by which the proposed method will be judged was examined. Extensive interaction with personnel from Computer Sciences Corporation and NASA Langley occurred to determine the requirements of the ATOPS software. Backward error recovery in concurrent systems was assessed.

  5. Design of an Ada expert system shell for the VHSIC avionic modular flight processor

    NASA Technical Reports Server (NTRS)

    Fanning, F. Jesse

    1992-01-01

    The Embedded Computer System Expert System Shell (ES Shell) is an Ada-based expert system shell developed at the Avionics Laboratory for use on the VHSIC Avionic Modular Processor (VAMP) running under the Ada Avionics Real-Time Software (AARTS) Operating System. The ES Shell provides the interface between the expert system and the avionics environment, and controls execution of the expert system. Testing of the ES Shell in the Avionics Laboratory's Integrated Test Bed (ITB) has demonstrated its ability to control a non-deterministic software application executing on the VAMP's which can control the ITB's real-time closed-loop aircraft simulation. The results of these tests and the conclusions reached in the design and development of the ES Shell have played an important role in the formulation of the requirements for a production-quality expert system inference engine, an ingredient necessary for the successful use of expert systems on the VAMP embedded avionic flight processor.

  6. Discrimination of Breast Tumors in Ultrasonic Images by Classifier Ensemble Trained with AdaBoost

    NASA Astrophysics Data System (ADS)

    Takemura, Atsushi; Shimizu, Akinobu; Hamamoto, Kazuhiko

    In this paper, we propose a novel method for acurate automated discrimination of breast tumors (carcinoma, fibroadenoma, and cyst). We defined 199 features related to diagnositic observations noticed when a doctor judges breast tumors, such as internal echo, shape, and boundary echo. These features included novel features based on a parameter of log-compressed K distribution, which reflect physical characteristics of ultrasonic B-mode imaging. Furthermore, we propose a discrimination method of breast tumors by using an ensemble classifier based on the multi-class AdaBoost algorithm with effective features selection. Verification by analyzing 200 carcinomas, 30 fibroadenomas and 30 cycts showed the usefulness of the newly defined features and the effectiveness of the discrimination by using an ensemble classifier trained by AdaBoost.

  7. Translating an AI application from Lisp to Ada: A case study

    NASA Technical Reports Server (NTRS)

    Davis, Gloria J.

    1991-01-01

    A set of benchmarks was developed to test the performance of a newly designed computer executing both Lisp and Ada. Among these was AutoClassII -- a large Artificial Intelligence (AI) application written in Common Lisp. The extraction of a representative subset of this complex application was aided by a Lisp Code Analyzer (LCA). The LCA enabled rapid analysis of the code, putting it in a concise and functionally readable form. An equivalent benchmark was created in Ada through manual translation of the Lisp version. A comparison of the execution results of both programs across a variety of compiler-machine combinations indicate that line-by-line translation coupled with analysis of the initial code can produce relatively efficient and reusable target code.

  8. Languages for artificial intelligence: Implementing a scheduler in LISP and in Ada

    NASA Technical Reports Server (NTRS)

    Hays, Dan

    1988-01-01

    A prototype scheduler for space experiments originally programmed in a dialect of LISP using some of the more traditional techniques of that language, was recast using an object-oriented LISP, Common LISP with Flavors on the Symbolics. This object-structured version was in turn partially implemented in Ada. The Flavors version showed a decided improvement in both speed of execution and readability of code. The recasting into Ada involved various practical problems of implementation as well as certain challenges of reconceptualization in going from one language to the other. Advantages were realized, however, in greater clarity of the code, especially where more standard flow of control was used. This exercise raised issues about the influence of programming language on the design of flexible and sensitive programs such as schedule planners, and called attention to the importance of factors external to the languages themselves such as system embeddedness, hardware context, and programmer practice.

  9. ADaM: augmenting existing approximate fast matching algorithms with efficient and exact range queries

    PubMed Central

    2014-01-01

    Background Drug discovery, disease detection, and personalized medicine are fast-growing areas of genomic research. With the advancement of next-generation sequencing techniques, researchers can obtain an abundance of data for many different biological assays in a short period of time. When this data is error-free, the result is a high-quality base-pair resolution picture of the genome. However, when the data is lossy the heuristic algorithms currently used when aligning next-generation sequences causes the corresponding accuracy to drop. Results This paper describes a program, ADaM (APF DNA Mapper) which significantly increases final alignment accuracy. ADaM works by first using an existing program to align "easy" sequences, and then using an algorithm with accuracy guarantees (the APF) to align the remaining sequences. The final result is a technique that increases the mapping accuracy from only 60% to over 90% for harder-to-align sequences. PMID:25079667

  10. Judge says sex is not a major life activity for purposes of ADA.

    PubMed

    1999-05-28

    A federal judge granted summary judgement to a retailer accused of firing an employee because he had hepatitis C. The employee alleged disability-based discrimination under the Americans with Disabilities Act (ADA). The ADA requires plaintiffs to show that they are "substantially limited" in "major life activities" such as self-care, walking, or working. The employee attempted to expand this definition, and claimed that he was limited in sexual reproduction. Although a previous court ruling allowed this claim, the judge took a narrow interpretation of the law. The judge held that sexual intercourse was not a major life activity, and that the plaintiff was not substantially limited by his hepatitis C to perform sexually or at work. PMID:11367138

  11. Real-time multi-camera video acquisition and processing platform for ADAS

    NASA Astrophysics Data System (ADS)

    Saponara, Sergio

    2016-04-01

    The paper presents the design of a real-time and low-cost embedded system for image acquisition and processing in Advanced Driver Assisted Systems (ADAS). The system adopts a multi-camera architecture to provide a panoramic view of the objects surrounding the vehicle. Fish-eye lenses are used to achieve a large Field of View (FOV). Since they introduce radial distortion of the images projected on the sensors, a real-time algorithm for their correction is also implemented in a pre-processor. An FPGA-based hardware implementation, re-using IP macrocells for several ADAS algorithms, allows for real-time processing of input streams from VGA automotive CMOS cameras.

  12. EEOC says temporary workers qualify for ADA protection. Equal Employment Opportunity Commission.

    PubMed

    1998-01-23

    The Equal Employment Opportunity Commission (EEOC) issued guidelines clarifying that both employers and staffing agencies can be held liable for discrimination and harassment of temporary or contingent workers. These workers are often viewed as independent contractors, and not employees. The guidance clarifies the employee-employer relationship, holding both the employment firm and the client accountable for discrimination and harassment and offering protection for this class of worker under the Americans with Disabilities Act (ADA) and other anti-discrimination statutes. The guidance also contains two case examples of how the ADA applies to contractual workers with HIV. The staffing firm and client each must count every worker with whom there is an employment relationship, and are prohibited from discriminating against each other's employees. PMID:11364955

  13. E-ADA activity in lymphocytes of an experimental model of pythiosis treated with immunotherapy.

    PubMed

    Bach, Barbara Charlotte; Leal, Daniela Bitencourt Rosa; Jaques, Jeandre Augusto dos Santos; Souza, Viviane do Carmo Gonçalves; Ruchel, Jader Betsch; Schlemmer, Karine Bizzi; Zanette, Régis Adriel; Hecktheuer, Pedro Abib; de Lima Pereira, Patrique; Casali, Emerson André; Alves, Sydney Hartz; Santurio, Janio Morais

    2013-08-01

    Pythiosis is a life-threatening disease caused by the oomycete Pythium insidiosum. Some authors have suggested the involvement of a Th2-like immune response in the infected host, which leads to extensive tissue damage. The switch from a Th2 to a Th1 response pattern is one hypothesis to explain the curative properties of immunotherapy. Taking into account the importance of immunotherapy for pythiosis treatment and the contribution of adenine nucleotides in the immunoregulation of the host, we evaluated the ecto-adenosine deaminase (E-ADA; EC 3·5.4·4) activity in lymphocytes from rabbits inoculated with P. insidiosum. Rabbits were inoculated with 1 milliliter of zoospores subcutaneously injected into the lateral thorax; after developing lesions, the rabbits received eight doses of immunotherapy. E-ADA activity was measured in lymphocytes and the adenine nucleotides and adenosine levels were quantitatively determined in serum. Rabbits with characteristic lesions of pythiosis showed a decreased E-ADA activity (82·36%), a decreased adenosine triphosphate concentration (54·04%) and a higher adenosine concentration (2·51 fold), when compared with controls, after 28 days of inoculation. However, after the immunotherapy, the rabbits showed an increase in the E-ADA activity when compared with control (78·62%), contributing for the change in the immune response. Our results reinforce the hypothesis that the change from a Th2 to a Th1 immune response with the participation of the purinergic system could be responsible for the curative properties of immunotherapy. PMID:23086808

  14. Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2

    PubMed Central

    Zhou, Q.; Yang, D.; Ombrello, A.K.; Zavialov, Andrey V.; Toro, C.; Zavialov, Anton V.; Stone, D.L.; Chae, J.J.; Rosenzweig, S.D.; Bishop, K.; Barron, K.S.; Kuehn, H.S.; Hoffmann, P.; Negro, A.; Tsai, W.L.; Cowen, E.W.; Pei, W.; Milner, J.D.; Silvin, C.; Heller, T.; Chin, D.T.; Patronas, N.J.; Barber, J.S.; Lee, C.-C.R.; Wood, G.M.; Ling, A.; Kelly, S.J.; Kleiner, D.E.; Mullikin, J.C.; Ganson, N.J.; Kong, H.H.; Hambleton, S.; Candotti, F.; Quezado, M.M.; Calvo, K.R.; Alao, H.; Barham, B.K.; Jones, A.; Meschia, J.F.; Worrall, B.B.; Kasner, S.E.; Rich, S.S.; Goldbach-Mansky, R.; Abinun, M.; Chalom, E.; Gotte, A.C.; Punaro, M.; Pascual, V.; Verbsky, J.W.; Torgerson, T.R.; Singer, N.G.; Gershon, T.R.; Ozen, S.; Karadag, O.; Fleisher, T.A.; Remmers, E.F.; Burgess, S.M.; Moir, S.L.; Gadina, M.; Sood, R.; Hershfield, M.S.; Boehm, M.; Kastner, D.L.; Aksentijevich, I.

    2014-01-01

    BACKGROUND We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood. METHODS We performed whole-exome sequencing in the initial three patients and their unaffected parents and candidate-gene sequencing in three patients with a similar phenotype, as well as two young siblings with polyarteritis nodosa and one patient with small-vessel vasculitis. Enzyme assays, immunoblotting, immunohistochemical testing, flow cytometry, and cytokine profiling were performed on samples from the patients. To study protein function, we used morpholino-mediated knockdowns in zebrafish and short hairpin RNA knockdowns in U937 cells cultured with human dermal endothelial cells. RESULTS All nine patients carried recessively inherited mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), encoding adenosine deaminase 2 (ADA2), that were predicted to be deleterious; these mutations were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations, whereas the three patients with polyarteritis nodosa or small-vessel vasculitis were homozygous for the p.Gly47Arg mutation. Patients had a marked reduction in the levels of ADA2 and ADA2-specific enzyme activity in the blood. Skin, liver, and brain biopsies revealed vasculopathic changes characterized by compromised endothelial integrity, endothelial cellular activation, and inflammation. Knockdown of a zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia — phenotypes that were prevented by coinjection with nonmutated (but not with mutated) human CECR1. Monocytes from patients induced damage in cocultured endothelial-cell layers. CONCLUSIONS Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes

  15. VIII Olimpíada Brasileira de Astronomia e Astronáutica

    NASA Astrophysics Data System (ADS)

    Garcia Canalle, João Batista; Villas da Rocha, Jaime Fernando; Wuensche de Souza, Carlos Alexandre; Pereira Ortiz, Roberto; Aguilera, Nuricel Villalonga; Padilha, Maria De Fátima Catta Preta; Pessoa Filho, José Bezerra; Soares Rodrigues, Ivette Maria

    2007-07-01

    Neste trabalho apresentamos as motivações pelas quais organizamos, em conjunto, pela primeira vez, a Olimpíada Brasileira de Astronomia incluindo a Astronáutica, em colaboração com a Agência Espacial Brasileira. Esta ampliação contribuiu para atrair ainda mais alunos, professores, escolas e patrocinadores para participarem desta Olimpíada. Em 2005 participaram da VIII Olimpíada Brasileira de Astronomia e Astronáutica (VIII OBA) 187.726 alunos distribuídos por 3.229 escolas, pertencentes a todos os estados brasileiros, incluindo o Distrito Federal. O crescimento em número de alunos participantes foi 52,4% maior do que em 2004. Em abril de 2005 organizamos, em Itapecerica da Serra, SP, um curso para os 50 alunos previamente selecionados e participantes da VII OBA e ao final selecionamos, dentre eles, uma equipe de 5 alunos, os quais representaram o Brasil na X Olimpíada Internacional de Astronomia, na China, em outubro de 2005. Ganhamos, pela primeira vez, uma medalha de ouro naquele evento. Em Agosto de 2005, organizamos a VIII Escola de Agosto para 50 alunos e respectivos professores, em Águas de Lindóia, SP, juntamente com a XXXI reunião anual da Sociedade Astronômica Brasileira (SAB). Em novembro de 2005 realizamos a I Jornada Espacial, em São José dos Campos, com 22 alunos e 22 professores selecionados dentre os participantes que melhores resultados obtiveram nas questões de Astronáutica da VIII OBA. Neste trabalho detalhamos os resultados da VIII OBA bem como as ações subseqüentes.

  16. Locus heterogeneity in autosomal dominant spinocerebellar ataxia: Evidence for the existence of a fifth locus

    SciTech Connect

    Sarrazin, J.; Rouleau, G.A.; Andermann, E.

    1994-09-01

    The autosomal dominantly inherited spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders. To date, four loci have been identified: the SCA-1 locus (on chromosome (chr) 6p), the SCA-2 locus (on chr 12q), the SCA-3/MJD locus (on chr 14q), and more recently an SCA-4 locus was described (chr 16q) in a Utah kindred. We have studied one large French Canadian kindred with four generations of living affected individuals segregating an autosomal dominant form of SCA. Linkage analysis using anonymous DNA markers which flank the four previously described loci significantly excludes the French Canadian kindred from the SCA-1, SCA-2, SCA-3/MJD and SCA-4 loci. Therefore a fifth, still unmapped, SCA locus remains to be identified.

  17. Ada (R) assessment: An important issue within European Columbus Support Technology Programme

    NASA Technical Reports Server (NTRS)

    Vielcanet, P.

    1986-01-01

    Software will be more important and more critical for Columbus than for any ESA previous project. As a simple comparison, overall software size has been in the range of 100 K source statements for EXOSAT, 500 K for Spacelab, and will probably reach several million lines of code for Columbus (all element together). Based on past experience, the total development cost of software can account for about 10 pct to 15 pct of the total space project development cost. The Ada technology may support the strong software engineering principles needed for Columbus, provided that technology is sufficiently mature and industry plans are meeting the Columbus project schedule. Over the past 3 years, Informatique Internationale has conducted a coherent program based on Ada technology assessment studies and experiments, for ESA and CNES. This specific research and development program benefits from 15 years experience in the field of space software development and is supported by the overall software engineering expertise of the company. The assessment and experiments of Ada software engineering by Informatique Internationale are detailed.

  18. Translating expert system rules into Ada code with validation and verification

    NASA Technical Reports Server (NTRS)

    Becker, Lee; Duckworth, R. James; Green, Peter; Michalson, Bill; Gosselin, Dave; Nainani, Krishan; Pease, Adam

    1991-01-01

    The purpose of this ongoing research and development program is to develop software tools which enable the rapid development, upgrading, and maintenance of embedded real-time artificial intelligence systems. The goals of this phase of the research were to investigate the feasibility of developing software tools which automatically translate expert system rules into Ada code and develop methods for performing validation and verification testing of the resultant expert system. A prototype system was demonstrated which automatically translated rules from an Air Force expert system was demonstrated which detected errors in the execution of the resultant system. The method and prototype tools for converting AI representations into Ada code by converting the rules into Ada code modules and then linking them with an Activation Framework based run-time environment to form an executable load module are discussed. This method is based upon the use of Evidence Flow Graphs which are a data flow representation for intelligent systems. The development of prototype test generation and evaluation software which was used to test the resultant code is discussed. This testing was performed automatically using Monte-Carlo techniques based upon a constraint based description of the required performance for the system.

  19. Software engineering and Ada (Trademark) training: An implementation model for NASA

    NASA Technical Reports Server (NTRS)

    Legrand, Sue; Freedman, Glenn

    1988-01-01

    The choice of Ada for software engineering for projects such as the Space Station has resulted in government and industrial groups considering training programs that help workers become familiar with both a software culture and the intricacies of a new computer language. The questions of how much time it takes to learn software engineering with Ada, how much an organization should invest in such training, and how the training should be structured are considered. Software engineering is an emerging, dynamic discipline. It is defined by the author as the establishment and application of sound engineering environments, tools, methods, models, principles, and concepts combined with appropriate standards, guidelines, and practices to support computing which is correct, modifiable, reliable and safe, efficient, and understandable throughout the life cycle of the application. Neither the training programs needed, nor the content of such programs, have been well established. This study addresses the requirements for training for NASA personnel and recommends an implementation plan. A curriculum and a means of delivery are recommended. It is further suggested that a knowledgeable programmer may be able to learn Ada in 5 days, but that it takes 6 to 9 months to evolve into a software engineer who uses the language correctly and effectively. The curriculum and implementation plan can be adapted for each NASA Center according to the needs dictated by each project.

  20. Using Ada to implement the operations management system in a community of experts

    NASA Technical Reports Server (NTRS)

    Frank, M. S.

    1986-01-01

    An architecture is described for the Space Station Operations Management System (OMS), consisting of a distributed expert system framework implemented in Ada. The motivation for such a scheme is based on the desire to integrate the very diverse elements of the OMS while taking maximum advantage of knowledge based systems technology. Part of the foundation of an Ada based distributed expert system was accomplished in the form of a proof of concept prototype for the KNOMES project (Knowledge-based Maintenance Expert System). This prototype successfully used concurrently active experts to accomplish monitoring and diagnosis for the Remote Manipulator System. The basic concept of this software architecture is named ACTORS for Ada Cognitive Task ORganization Scheme. It is when one considers the overall problem of integrating all of the OMS elements into a cooperative system that the AI solution stands out. By utilizing a distributed knowledge based system as the framework for OMS, it is possible to integrate those components which need to share information in an intelligent manner.

  1. AdaFF: Adaptive Failure-Handling Framework for Composite Web Services

    NASA Astrophysics Data System (ADS)

    Kim, Yuna; Lee, Wan Yeon; Kim, Kyong Hoon; Kim, Jong

    In this paper, we propose a novel Web service composition framework which dynamically accommodates various failure recovery requirements. In the proposed framework called Adaptive Failure-handling Framework (AdaFF), failure-handling submodules are prepared during the design of a composite service, and some of them are systematically selected and automatically combined with the composite Web service at service instantiation in accordance with the requirement of individual users. In contrast, existing frameworks cannot adapt the failure-handling behaviors to user's requirements. AdaFF rapidly delivers a composite service supporting the requirement-matched failure handling without manual development, and contributes to a flexible composite Web service design in that service architects never care about failure handling or variable requirements of users. For proof of concept, we implement a prototype system of the AdaFF, which automatically generates a composite service instance with Web Services Business Process Execution Language (WS-BPEL) according to the users' requirement specified in XML format and executes the generated instance on the ActiveBPEL engine.

  2. The implementation and use of ADA on distributed systems with high reliability requirements

    NASA Technical Reports Server (NTRS)

    Knight, J. C.

    1985-01-01

    The use and implementation of Ada in distributed environments in which reliability is the primary concern is investigated. Emphasis is placed on the possibility that a distributed system may be programmed entirely in Ada so that the individual tasks of the system are unconcerned with which processors they are executing on, and that failures may occur in the software or underlying hardware. A new linguistic construct, the colloquy, is introduced which solves the problems identified in an earlier proposal, the conversation. It was shown that the colloquy is at least as powerful as recovery blocks, but it is also as powerful as all the other language facilities proposed for other situations requiring backward error recovery: recovery blocks, deadlines, generalized exception handlers, traditional conversations, s-conversations, and exchanges. The major features that distinguish the colloquy are described. Sample programs that were written, but not executed, using the colloquy show that extensive backward error recovery can be included in these programs simply and elegantly. These ideas are being implemented in an experimental Ada test bed.

  3. 9th Circuit says engaging in sex is a major life activity under ADA.

    PubMed

    1999-10-01

    The 9th U.S. Circuit Court of Appeals ruled that the ability to engage in sexual relations is a major life activity under the definition of the Americans with Disabilities Act (ADA). The ruling suggests that all adults and adolescents infected with HIV are covered by the ADA because of the risk of transmitting the virus sexually. The U.S. Supreme Court ruled last year in the [name removed] v. [Name removed] case that the ability to procreate is a major life activity, but it left unresolved the issue of whether sexual relations were covered. Several other courts have further defined the issue and ruled that sexual dysfunction should count as a disability. The plaintiff in this case sued after his employer refused to relocate him to a different department, stating he was deprived of a reasonable accommodation. The plaintiff suffered from impotence, and claimed a disability under the ADA. The dissenting judge in the ruling noted that he did not see how one's ability to have sexual relations had any connection to employment. PMID:11367019

  4. Effect of locus of control on disordered eating in athletes: the mediational role of self-regulation of eating attitudes.

    PubMed

    Scoffier, S; Paquet, Y; d'Arripe-Longueville, F

    2010-08-01

    This study examined the influence of locus of control on disordered eating as mediated by the self-regulation of eating attitudes. The assessment instruments were adapted for athletes as the entire sample of 179 volunteer University students (M(age)=21.12; SD=2.87) were all regularly involved in competition. The results showed that (a) an internal locus of control had a positive influence on the self-regulation of eating attitudes in social interaction contexts; (b) self-regulatory eating attitudes had a negative influence on disordered eating in contexts of negative affect, social interaction, and lack of anticipation of consequences on performance; and (c) an internal locus of control had an influence on disordered eating through the mediation of self-regulatory eating attitudes in social interaction contexts, and an external locus of control attributed to the coach and sports friends had an influence on disordered eating through the mediation of self-regulatory eating attitudes in contexts of negative affect, social interaction and lack of anticipation of consequences on performance. This study, combined with an earlier study from Scoffier, Maïano, and d'Arripe-Longueville (2009) on the antecedents of athletes' eating disorders, suggests the powerful impact of the social environment on the development of disordered eating in athletes.

  5. Effect of locus of control on disordered eating in athletes: the mediational role of self-regulation of eating attitudes.

    PubMed

    Scoffier, S; Paquet, Y; d'Arripe-Longueville, F

    2010-08-01

    This study examined the influence of locus of control on disordered eating as mediated by the self-regulation of eating attitudes. The assessment instruments were adapted for athletes as the entire sample of 179 volunteer University students (M(age)=21.12; SD=2.87) were all regularly involved in competition. The results showed that (a) an internal locus of control had a positive influence on the self-regulation of eating attitudes in social interaction contexts; (b) self-regulatory eating attitudes had a negative influence on disordered eating in contexts of negative affect, social interaction, and lack of anticipation of consequences on performance; and (c) an internal locus of control had an influence on disordered eating through the mediation of self-regulatory eating attitudes in social interaction contexts, and an external locus of control attributed to the coach and sports friends had an influence on disordered eating through the mediation of self-regulatory eating attitudes in contexts of negative affect, social interaction and lack of anticipation of consequences on performance. This study, combined with an earlier study from Scoffier, Maïano, and d'Arripe-Longueville (2009) on the antecedents of athletes' eating disorders, suggests the powerful impact of the social environment on the development of disordered eating in athletes. PMID:20434063

  6. Parallel Ada implementation of a multiple-model Kalman-filter tracking system: a software engineering approach. Master's thesis

    SciTech Connect

    Lemanski, W.J.

    1989-03-01

    The success of the Strategic Defense Initiative depends directly on significant advances in both computer hardware and software development technologies. Parallel architectures and the Ada programming language have advantages that make them candidates for use in SDI command and control computer systems. This thesis examines those advantages in the context of an SDI-type application: implementation of a Kalman-filter tracking system. This research consists of three parts. The first is a set of software engineering guidelines developed for use in creating parallel designs suitable for implementation in Ada. These guidelines cover the design process from initial problem analysis to final detailed design. Methods of problem decomposition are discussed, as are language partitioning strategies. Justification is provided for using the Ada task construct for process boundaries, and Ada multitasking design issues are reviewed. A parallel software design methodology is also described.

  7. Mutations affecting expression of the rosy locus in Drosophila melanogaster

    SciTech Connect

    Lee, C.S.; Curtis, D.; McCarron, M.; Love, C.; Gray, M.; Bender, W.; Chovnick, A.

    1987-05-01

    The rosy locus in Drosophila melanogaster codes for the enzyme xanthine dehydrogenase (XDH). Previous studies defined a control element near the 5' end of the gene, where variant sites affected the amount of rosy mRNA and protein produced. The authors have determined the DNA sequence of this region from both genomic and cDNA clones, and from the ry/sup +10/ underproducer strain. This variant strain had many sequence differences, so that the site of the regulatory change could not be fixed. A mutagenesis was also undertaken to isolate new regulatory mutations. They induced 376 new mutations with 1-ethyl-1-nitrosourea (ENU) and screened them to isolate those that reduced the amount of XDH protein produced, but did not change the properties of the enzyme. Genetic mapping was used to find mutations located near the 5' end of the gene. DNA from each of seven mutants was cloned and sequenced through the 5' region. Mutant base changes were identified in all seven; they appear to affect splicing and translation of the rosy mRNA. In a related study, the genomic and cDNA sequences are extended through the 3' end of the gene; the combined sequences define the processing pattern of the rosy transcript and predict the amino acid sequence of XDH.

  8. Enhancer scanning to locate regulatory regions in genomic loci

    PubMed Central

    Buckley, Melissa; Gjyshi, Anxhela; Mendoza-Fandiño, Gustavo; Baskin, Rebekah; Carvalho, Renato S.; Carvalho, Marcelo A.; Woods, Nicholas T.; Monteiro, Alvaro N.A.

    2016-01-01

    The present protocol provides a rapid, streamlined and scalable strategy to systematically scan genomic regions for the presence of transcriptional regulatory regions active in a specific cell type. It creates genomic tiles spanning a region of interest that are subsequently cloned by recombination into a luciferase reporter vector containing the Simian Virus 40 promoter. Tiling clones are transfected into specific cell types to test for the presence of transcriptional regulatory regions. The protocol includes testing of different SNP (single nucleotide polymorphism) alleles to determine their effect on regulatory activity. This procedure provides a systematic framework to identify candidate functional SNPs within a locus during functional analysis of genome-wide association studies. This protocol adapts and combines previous well-established molecular biology methods to provide a streamlined strategy, based on automated primer design and recombinational cloning to rapidly go from a genomic locus to a set of candidate functional SNPs in eight weeks. PMID:26658467

  9. ADA Design.

    ERIC Educational Resources Information Center

    Gips, Kathy

    2003-01-01

    Describes requirements for existing educational facilities under Title II of the Americans with Disabilities Act and addresses issues such as guidelines for children, wheelchair-accessible and ambulatory stalls, areas without their own section in the standards, assistive listening devices in auditoriums, ramp slope, emergency evacuation planning,…

  10. Locus of Control in Alcoholics Undergoing Treatment.

    ERIC Educational Resources Information Center

    Haley, Shirley C.

    Alcoholism is a complex behavior pattern. Social learning theory, which is concerned with the analysis of why individuals behave in certain ways and the effects of reinforcement patterns in their behaviors, offers an alternative to traditional treatments of alcoholics. Among alcoholics, drinking is a control issue. Locus of control is viewed as a…

  11. Aspirations, Attributions, and Locus of Control.

    ERIC Educational Resources Information Center

    Samuel, William; McNall, Sidne J.

    Self-evaluation is thought to play a major role in personality and motivation. Preliminary experience with success or failure, levels of aspiration, attributions for performance, and locus of control may all be interrelated factors in human motivation. After receiving success, failure, or no feedback on a concept formation task, subjects (N=90)…

  12. A suppressor locus for MODY3-diabetes

    PubMed Central

    Garcia-Gonzalez, Miguel A.; Carette, Claire; Bagattin, Alessia; Chiral, Magali; Makinistoglu, Munevver Parla; Garbay, Serge; Prévost, Géraldine; Madaras, Cécile; Hérault, Yann; Leibovici, Michel; Pontoglio, Marco

    2016-01-01

    Maturity Onset Diabetes of the Young type 3 (MODY3), linked to mutations in the transcription factor HNF1A, is the most prevalent form of monogenic diabetes mellitus. HNF1alpha-deficiency leads to defective insulin secretion via a molecular mechanism that is still not completely understood. Moreover, in MODY3 patients the severity of insulin secretion can be extremely variable even in the same kindred, indicating that modifier genes may control the onset of the disease. With the use of a mouse model for HNF1alpha-deficiency, we show here that specific genetic backgrounds (C3H and CBA) carry a powerful genetic suppressor of diabetes. A genome scan analysis led to the identification of a major suppressor locus on chromosome 3 (Moda1). Moda1 locus contains 11 genes with non-synonymous SNPs that significantly interacts with other loci on chromosomes 4, 11 and 18. Mechanistically, the absence of HNF1alpha in diabetic-prone (sensitive) strains leads to postnatal defective islets growth that is remarkably restored in resistant strains. Our findings are relevant to human genetics since Moda1 is syntenic with a human locus identified by genome wide association studies of fasting glycemia in patients. Most importantly, our results show that a single genetic locus can completely suppress diabetes in Hnf1a-deficiency. PMID:27667715

  13. Surfeit locus gene homologs are widely distributed in invertebrate genomes.

    PubMed

    Armes, N; Fried, M

    1996-10-01

    The mouse Surfeit locus contains six sequence-unrelated genes (Surf-1 to -6) arranged in the tightest gene cluster so far described for mammals. The organization and juxtaposition of five of the Surfeit genes (Surf-1 to -5) are conserved between mammals and birds, and this may reflect a functional or regulatory requirement for the gene clustering. We have undertaken an evolutionary study to determine whether the Surfeit genes are conserved and clustered in invertebrate genomes. Drosophila melanogaster and Caenorhabditis elegans homologs of the mouse Surf-4 gene, which encodes an integral membrane protein associated with the endoplasmic reticulum, have been isolated. The amino acid sequences of the Drosophila and C. elegans homologs are highly conserved in comparison with the mouse Surf-4 protein. In particular, a dilysine motif implicated in endoplasmic reticulum localization of the mouse protein is conserved in the invertebrate homologs. We show that the Drosophila Surf-4 gene, which is transcribed from a TATA-less promoter, is not closely associated with other Drosophila Surfeit gene homologs but rather is located upstream from sequences encoding a homolog of a yeast seryl-tRNA synthetase protein. There are at least two closely linked Surf-3/rpL7a genes or highly polymorphic alleles of a single Surf-3/rpL7a gene in the C. elegans genome. The chromosomal locations of the C. elegans Surf-1, Surf-3/rpL7a, and Surf-4 genes have been determined. In D. melanogaster the Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs and in C. elegans the Surf-1, Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs are located on completely different chromosomes, suggesting that any requirement for the tight clustering of the genes in the Surfeit locus is restricted to vertebrate lineages.

  14. The potato R locus codes for dihydroflavonol 4-reductase.

    PubMed

    Zhang, Yongfei; Cheng, Shuping; De Jong, Darlene; Griffiths, Helen; Halitschke, Rayko; De Jong, Walter

    2009-09-01

    The potato R locus is required for the production of red pelargonidin-based anthocyanin pigments in potato (Solanum tuberosum L.). Red color also requires tissue-specific regulatory genes, such as D (for expression in tuber skin) and F (expression in flowers). A related locus, P, is required for production of blue/purple anthocyanins; P is epistatic to R. We have previously reported that the dihydroflavonol 4-reductase gene (dfr) co-segregates with R. To test directly whether R corresponds to dfr, we placed the allele of dfr associated with red color under the control of the CaMV 35S promoter and introduced it into the potato cultivar Prince Hairy (genotype dddd rrrr P-), which has white tubers and pale blue flowers. Transgenic Prince Hairy tubers remained white, but flower color changed to purple. Three independent transgenic lines, as well as a vector-transformed line, were then crossed with the red-skinned variety Chieftain (genotype D-R-pppp), to establish populations that segregated for D, R, P, and the dfr transgene or empty vector. Markers were used to genotype progeny at D and R. Progeny carrying the empty vector in the genetic background D-rrrr produced white or purple tubers, while progeny with the same genotype and the dfr transgene produced red or purple tubers. HPLC and LC-MS/MS analyses of anthocyanins present in Chieftain and in a red-skinned progeny clone with the dfr transgene in a D-rrrr background revealed no qualitative differences. Thus, dfr can fully complement R, both in terms of tuber color and anthocyanin composition.

  15. Regulatory Anatomy

    PubMed Central

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, legal documents, technological devices, organizational structures, and work practices aimed at minimizing risk. I use this term to reorient the analytical attention with respect to safety regulation. Instead of evaluating whether safety is achieved, the point is to explore the types of “safety” produced through these logics as well as to consider the sometimes unintended consequences of such safety work. In fact, the EU rules have been giving rise to complaints from practitioners finding the directives problematic and inadequate. In this article, I explore the problems practitioners face and why they arise. In short, I expose the regulatory anatomy of the policy landscape. PMID:26139952

  16. Regulatory RNAs

    PubMed Central

    Vazquez-Anderson, Jorge; Contreras, Lydia M

    2013-01-01

    RNAs have many important functional properties, including that they are independently controllable and highly tunable. As a result of these advantageous properties, their use in a myriad of sophisticated devices has been widely explored. Yet, the exploitation of RNAs for synthetic applications is highly dependent on the ability to characterize the many new molecules that continue to be discovered by large-scale sequencing and high-throughput screening techniques. In this review, we present an exhaustive survey of the most recent synthetic bacterial riboswitches and small RNAs while emphasizing their virtues in gene expression management. We also explore the use of these RNA components as building blocks in the RNA synthetic biology toolbox and discuss examples of synthetic RNA components used to rewire bacterial regulatory circuitry. We anticipate that this field will expand its catalog of smart devices by mimicking and manipulating natural RNA mechanisms and functions. PMID:24356572

  17. Regulatory Physiology

    NASA Technical Reports Server (NTRS)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  18. The implementation and use of Ada on distributed systems with high reliability requirements

    NASA Technical Reports Server (NTRS)

    Knight, J. C.

    1987-01-01

    A preliminary analysis of the Ada implementation of the Advanced Transport Operating System (ATOPS), an experimental computer control system developed at NASA Langley for a modified Boeing 737 aircraft, is presented. The criteria that was determined for the evaluation of this approach is described. A preliminary version of the requirements for the ATOPS is contained. This requirements specification is not a formal document, but rather a description of certain aspects of the ATOPS system at a level of detail that best suits the needs of the research. The survey of backward error recovery techniques is also presented.

  19. Stereospecific removal of methyl phosphotriesters from DNA by an Escherichia coli ada+ extract.

    PubMed

    Weinfeld, M; Drake, A F; Saunders, J K; Paterson, M C

    1985-10-11

    The ada+ gene product, a DNA methyltransferase present in extracts from an Escherichia coli strain constitutive for the adaptive response, removes only half of the methyl phosphotriesters from alkylated DNA. Since DNA phosphotriesters occur in two isomeric configurations (denoted Rp and Sp), we examined whether this reflects a stereospecific mode of repair by the methyltransferase. Analysis by reverse-phase HPLC, phosphorus NMR and circular dichroism established that only triesters in the Sp configuration are acted upon by the E. coli extract. PMID:3903661

  20. Detection of coronal mass ejections using AdaBoost on grayscale statistic features

    NASA Astrophysics Data System (ADS)

    Zhang, Ling; Yin, Jian-qin; Lin, Jia-ben; Wang, Xiao-fan; Guo, Juan

    2016-10-01

    We present an automatic algorithm to detect coronal mass ejections (CMEs) in Large Angle Spectrometric Coronagraph (LASCO) C2 running difference images. The algorithm includes 3 steps: (1) split the running difference images into blocks according to slice size and analyze the grayscale statistics of the blocks from a set of images with and without CMEs; (2) select the optimal parameters for slice size, gray threshold and fraction of the bright points and (3) use AdaBoost to combine the weak classifiers designed according to the optimal parameters. Experimental results show that our method is effective and has a high accuracy rate.

  1. Ground-water quality in northern Ada County, lower Boise River basin, Idaho, 1985-96

    USGS Publications Warehouse

    Parliman, D.J.; Spinazola, Joseph M.

    1998-01-01

    In October 1992, the U.S. Geological Survey (USGS), in cooperation with the Idaho Division of Environmental Quality, Boise Regional Office (IDEQ-BRO), began a comprehensive study of ground-water quality in the lower Boise River Basin. The study in northern Ada County has been completed, and this report presents selected results of investigations in that area. Results and discussion presented herein are based on information in publications listed under “References Cited” on the last page of this Fact Sheet.

  2. An Ada Linear-Algebra Software Package Modeled After HAL/S

    NASA Technical Reports Server (NTRS)

    Klumpp, Allan R.; Lawson, Charles L.

    1990-01-01

    New avionics software written more easily. Software package extends Ada programming language to include linear-algebra capabilities similar to those of HAL/S programming language. Designed for such avionics applications as Space Station flight software. In addition to built-in functions of HAL/S, package incorporates quaternion functions used in Space Shuttle and Galileo projects and routines from LINPAK solving systems of equations involving general square matrices. Contains two generic programs: one for floating-point computations and one for integer computations. Written on IBM/AT personal computer running under PC DOS, v.3.1.

  3. Development of Ada language control software for the NASA power management and distribution test bed

    NASA Technical Reports Server (NTRS)

    Wright, Ted; Mackin, Michael; Gantose, Dave

    1989-01-01

    The Ada language software developed to control the NASA Lewis Research Center's Power Management and Distribution testbed is described. The testbed is a reduced-scale prototype of the electric power system to be used on space station Freedom. It is designed to develop and test hardware and software for a 20-kHz power distribution system. The distributed, multiprocessor, testbed control system has an easy-to-use operator interface with an understandable English-text format. A simple interface for algorithm writers that uses the same commands as the operator interface is provided, encouraging interactive exploration of the system.

  4. Software issues involved in code translation of C to Ada programs

    NASA Technical Reports Server (NTRS)

    Hooi, Robert; Giarratano, Joseph

    1986-01-01

    It is often thought that translation of one programming language to another is a simple solution that can be used to extend the software life span or in rehosting software to another environment. The possible problems are examined as are the advantages and disadvantages of direct machine or human code translation versus that of redesign and rewrite of the software. The translation of the expert system language called C Language Integrated Production System (CLIPS) which is written in C, to Ada, will be used as a case study of the problems that are encountered.

  5. Locus of Control and Psychological Distress among the Aged.

    ERIC Educational Resources Information Center

    Hale, W. Daniel; And Others

    1986-01-01

    Examined relationship between locus of control and self-reported psychopathology in 139 residents of retirement complex. Correlation coefficients computed for locus of control and each of nine symptom dimensions of the Brief Symptom Inventory indicated that locus of control was correlated with self-reported psychopatholgoy for older women but not…

  6. Cognitive Evaluation Theory, Locus of Control and Positive Verbal Feedback.

    ERIC Educational Resources Information Center

    Lonky, Edward; Reihman, Jacqueline

    This study tests the hypothesis that individual differences in locus of control orientation may mediate elementary school students' responses to positive verbal feedback. A total of 30 kindergarten through fourth grade subjects were assessed for locus of control orientation using the Bialer Children's Locus of Control Questionnaire. To establish a…

  7. Evolution of sex-specific wing shape at the widerwing locus in four species of Nasonia.

    PubMed

    Loehlin, D W; Enders, L S; Werren, J H

    2010-03-01

    How do morphological differences between species evolve at the genetic level? This study investigates the genetic basis of recent divergence in male wing size between species of the model parasitoid wasp Nasonia. The forewings of flightless Nasonia vitripennis males are 2.3 times smaller than males of their flighted sister species N. giraulti. We describe a major genetic contributor to this difference: the sex-specific widerwing (wdw) locus, which we have backcrossed from N. giraulti into N. vitripennis and mapped to an 0.9 megabase region of chromosome 1. This introgression of wdw from large-winged N. giraulti into small-winged N. vitripennis increases male but not female forewing width by 30% through wing region-specific size changes. Indirect evidence suggests that cell number changes across the wing explain the majority of the wdw wing-size difference, whereas changes in cell size are important in the center of the wing. Introgressing the same locus from the other species in the genus, N. longicornis and N. oneida, into N. vitripennis produces intermediate and large male wing sizes. To our knowledge, this is the first study to introgress a morphological quantitative trait locus (QTL) from multiple species into a common genetic background. Epistatic interactions between wdw and other QTL are also identified by introgressing wdw from N. vitripennis into N. giraulti. The main findings are (1) the changes at wdw have sex- and region-specific effects and could, therefore, be regulatory, (2) the wdw locus seems to be a co-regulator of cell size and cell number, and (3) the wdw locus has evolved different wing width effects in three species.

  8. Evolution of sex-specific wing shape at the widerwing locus in four species of Nasonia

    PubMed Central

    Loehlin, David W.; Enders, Laramy S.; Werren, John H.

    2009-01-01

    How do morphological differences between species evolve at the genetic level? This study investigates the genetic basis of recent divergence in male wing size between species of the model parasitoid wasp Nasonia. The forewings of flightless N. vitripennis males are 2.3 times smaller than males of their flighted sister species N. giraulti. We describe a major genetic contributor to this difference: the sex-specific widerwing (wdw) locus, which we have backcrossed from N. giraulti into N. vitripennis and mapped to an 0.9 megabase region of chromosome 1. This introgression of wdw from large-winged N. giraulti into small-winged N. vitripennis increases male but not female forewing width by 30% through wing region-specific size changes. Indirect evidence suggests that cell number changes across the wing explain the majority of the wdw wing size difference while changes in cell size are important in the center of the wing. Introgressing the same locus from the other species in the genus, N. longicornis and N. oneida, into N. vitripennis produces intermediate and large male wing sizes. To our knowledge, this is the first study to introgress a morphological quantitative trait locus (QTL) from multiple species into a common genetic background. Epistatic interactions between wdw and other QTL are also identified by introgressing wdw from N. vitripennis into N. giraulti. The main findings are 1) the changes at wdw have sex- and region-specific effects and could therefore be regulatory, 2) the wdw locus appears to be a co-regulator of cell size and cell number, and 3) the wdw locus has evolved different wing width effects in three species. PMID:20087390

  9. Interaction of the Stubble-Stubbloid Locus and the Broad-Complex of Drosophila Melanogaster

    PubMed Central

    Beaton, A. H.; Kiss, I.; Fristrom, D.; Fristrom, J. W.

    1988-01-01

    The 2B5 region on the X chromosome of Drosophila melanogaster forms an early ecdysone puff at the end of the third instar. The region is coextensive with a complex genetic locus, the Broad-Complex (BR-C). The BR-C is a regulatory gene that contains two major functional domains, the br domain and the l(1)2Bc domain. BR-C mutants prevent metamorphosis, including morphogenesis of imaginal discs; br mutants prevent elongation and eversion of appendages and l(1)2Bc mutants prevent fusion of the discs. The Stubble-stubbloid (Sb-sbd) locus at 89B9-10 is best known for the effects of its mutants on bristle structure. Mutants of the BR-C and the Sb-sbd locus interact to produce severe malformation of appendages. Viable heteroallelic and homoallelic combinations of Sb-sbd mutants, including loss-of-function mutants, affect the elongation of imaginal disc appendages. Thus, the Sb-sbd(+) product is essential for normal appendage elongation. Sb-sbd mutants, however, do not affect eversion or fusion of discs. Correspondingly, only BR-C mutants deficient in br function interact with Sb-sbd mutants. The interaction occurs in deficiency heterozygotes using single, wild-type doses of the BR-C, of the Sb-sbd locus, or of both loci. These last results are formally consistent with the possibility that the BR-C acts as a positive regulator of the Sb-sbd locus. The data do not exclude other possible nonregulatory interactions between the two loci, e.g., interactions between the products of both genes. PMID:3143619

  10. Recurrent Somatic Mutations in Regulatory Regions of Human Cancer Genomes

    PubMed Central

    Melton, Collin; Reuter, Jason A.; Spacek, Damek V.; Snyder, Michael

    2015-01-01

    Aberrant regulation of gene expression in cancer can promote survival and proliferation of cancer cells. Here we integrate TCGA whole genome sequencing data of 436 patients from eight cancer subtypes with ENCODE and other regulatory annotations to identify point mutations in regulatory regions. We find evidence for positive selection of mutations in transcription factor binding sites, consistent with these sites regulating important cancer cell functions. Using a novel method that adjusts for sample- and genomic locus-specific mutation rate, we identify recurrently mutated sites across cancer patients. Mutated regulatory sites include known sites in the TERT promoter and many novel sites, including a subset in proximity to cancer genes. In reporter assays, two novel sites display decreased enhancer activity upon mutation. These data demonstrate that many regulatory regions contain mutations under selective pressure and suggest a larger role for regulatory mutations in cancer than previously appreciated. PMID:26053494

  11. Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE

    PubMed Central

    Bekris, L.M.; Lutz, F.; Yu, C.E.

    2011-01-01

    Genetic variation within the apolipoprotein E gene (APOE) locus is associated with late-onset Alzheimer's disease risk and quantitative traits as well as apoE expression in multiple tissues. The aim of this investigation was to explore the influence of APOE locus cis-regulatory element enhancer region genetic variation on regional gene promoter activity. Luciferase reporter constructs containing haplotypes of APOE locus gene promoters; APOE, APOC1, and TOMM40, and regional putative enhancers; TOMM40 IVS2-4, TOMM40 IVS6 poly-T, as well as previously described enhancers; ME1, or BCR, were evaluated for their effects on luciferase activity in 3 human cell lines. Results of this investigation demonstrate that in SHSY5Y cells, the APOE promoter is significantly influenced by the TOMM40 IVS2-4 and ME1 and the TOMM40 promoter is significantly influenced by the TOMM40 IVS6 poly-T, ME1 and BCR. In HepG2 cells, theTOMM40 promoter is significantly influenced by all four enhancers, whereas the APOE promoter is not influenced by any of the enhancers. The main novel finding of this investigation was that multiple APOE locus cis-elements influence both APOE and TOMM40 promoter activity according to haplotype and cell type suggesting that a complex transcriptional regulatory structure modulates regional expression. PMID:22089642

  12. Generic Ada code in the NASA space station command, control and communications environment

    NASA Technical Reports Server (NTRS)

    Mcdougall, D. P.; Vollman, T. E.

    1986-01-01

    The results of efforts to apply powerful Ada constructs to the formatted message handling process are described. The goal of these efforts was to extend the state-of-technology in message handling while at the same time producing production-quality, reusable code. The first effort was initiated in September, 1984 and delivered in April, 1985. That product, the Generic Message Handling Facility, met initial goals, was reused, and is available in the Ada Repository on ARPANET. However, it became apparent during its development that the initial approach to building a message handler template was not optimal. As a result of this initial effort, several alternate approaches were identified, and research is now on-going to identify an improved product. The ultimate goal is to be able to instantly build a message handling system for any message format given a specification of that message format. The problem lies in how to specify the message format, and one that is done, how to use that information to build the message handler. Message handling systems and message types are described. The initial efforts, its results and its shortcomings are detailed. The approach now being taken to build a system which will be significantly easier to implement, and once implemented, easier to use, is described. Finally, conclusions are offered.

  13. Mason Tenders agrees to pay $1 million to end ADA litigation.

    PubMed

    1995-12-29

    The [name removed] District Council Welfare Fund has agreed to pay $1 million to construction workers who have been denied medical coverage for AIDS-related care. The decision establishes self-insured health care benefits programs as covered entities under the Americans with Disabilities Act (ADA). The settlement ends a three-year battle which began in 1992 between [name removed] and fourteen HIV-positive construction workers who were refused medical coverage. The first suit was filed by [name removed]., a construction worker who lost coverage for his HIV-related care in July 1991. At that time, the union fund decided to exclude care for HIV on the grounds that it was too expensive. The Equal Employment Opportunity Commission (EEOC) filed an ADA lawsuit that challenged disability-based distinctions in health insurance. The U.S. Attorney's Office filed a complaint against the union under the Racketeer Influenced and Corrupt Organizations (RICO) statute to end organized crime associated with the union. In late 1994, the government announced a consent decree, settling its racketeering suit against the union. Under the terms of the settlement, [name removed] was awarded $16,000 in damages. In the EEOC case, damages for plan members ranged as high as $50,000.

  14. Integrating automated structured analysis and design with Ada programming support environments

    NASA Technical Reports Server (NTRS)

    Hecht, Alan; Simmons, Andy

    1986-01-01

    Ada Programming Support Environments (APSE) include many powerful tools that address the implementation of Ada code. These tools do not address the entire software development process. Structured analysis is a methodology that addresses the creation of complete and accurate system specifications. Structured design takes a specification and derives a plan to decompose the system subcomponents, and provides heuristics to optimize the software design to minimize errors and maintenance. It can also produce the creation of useable modules. Studies have shown that most software errors result from poor system specifications, and that these errors also become more expensive to fix as the development process continues. Structured analysis and design help to uncover error in the early stages of development. The APSE tools help to insure that the code produced is correct, and aid in finding obscure coding errors. However, they do not have the capability to detect errors in specifications or to detect poor designs. An automated system for structured analysis and design TEAMWORK, which can be integrated with an APSE to support software systems development from specification through implementation is described. These tools completement each other to help developers improve quality and productivity, as well as to reduce development and maintenance costs. Complete system documentation and reusable code also resultss from the use of these tools. Integrating an APSE with automated tools for structured analysis and design provide capabilities and advantages beyond those realized with any of these systems used by themselves.

  15. Using AppletMagic(tm) to Implement an Orbit Propagator: New Life for Ada Objects

    NASA Technical Reports Server (NTRS)

    Stark, Michael E.

    1997-01-01

    This paper will discuss the use of the Intermetrics AppletMagic tool to build an applet to display a satellite ground track on a world map. This applet is the result of a prototype project that was developed by the Goddard Space Flight Center's Flight Dynamics Division (FDD), starting in June of 1996. Both Version 1 and Version 2 of this applet can be accessed via the URL http://fdd.gsfc.nasa.gov/Java.html. This paper covers Version 1, as Version 2 did not make radical changes to the Ada part of the applet. This paper will briefly describe the design of the applet, discuss the issues that arose during development, and will conclude with lessons learned and future plans for the FDD's use of Ada and Java. The purpose of this paper is to show examples of a successful project using Oi AppletMagic, and to highlight some of the pitfalls that occurred along the way. It is hoped that this discussion will be useful both to users of AppletMagic and to organizations such as Intermetrics that develop new technology.

  16. Polycomb Mediated Epigenetic Silencing and Replication Timing at the INK4a/ARF Locus during Senescence

    PubMed Central

    Verthuy, Christophe; Chasson, Lionel; Serrano, Manuel; Djabali, Malek

    2009-01-01

    Background The INK4/ARF locus encodes three tumor suppressor genes (p15Ink4b, Arf and p16Ink4a) and is frequently inactivated in a large number of human cancers. Mechanisms regulating INK4/ARF expression are not fully characterized. Principal Findings Here we show that in young proliferating embryonic fibroblasts (MEFs) the Polycomb Repressive Complex 2 (PRC2) member EZH2 together with PRC1 members BMI1 and M33 are strongly expressed and localized at the INK4/ARF regulatory domain (RD) identified as a DNA replication origin. When cells enter senescence the binding to RD of both PRC1 and PRC2 complexes is lost leading to a decreased level of histone H3K27 trimethylation (H3K27me3). This loss is accompanied with an increased expression of the histone demethylase Jmjd3 and with the recruitment of the MLL1 protein, and correlates with the expression of the Ink4a/Arf genes. Moreover, we show that the Polycomb protein BMI1 interacts with CDC6, an essential regulator of DNA replication in eukaryotic cells. Finally, we demonstrate that Polycomb proteins and associated epigenetic marks are crucial for the control of the replication timing of the INK4a/ARF locus during senescence. Conclusions We identified the replication licencing factor CDC6 as a new partner of the Polycomb group member BMI1. Our results suggest that in young cells Polycomb proteins are recruited to the INK4/ARF locus through CDC6 and the resulting silent locus is replicated during late S-phase. Upon senescence, Jmjd3 is overexpressed and the MLL1 protein is recruited to the locus provoking the dissociation of Polycomb from the INK4/ARF locus, its transcriptional activation and its replication during early S-phase. Together, these results provide a unified model that integrates replication, transcription and epigenetics at the INK4/ARF locus. PMID:19462008

  17. Neuroanatomical correlates of the sense of control: Gray and white matter volumes associated with an internal locus of control.

    PubMed

    Hashimoto, Teruo; Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Kawashima, Ryuta

    2015-10-01

    A belief that effort is rewarded can develop incentive, achievement motivation, and self-efficacy. Individuals with such a belief attribute causes of events to themselves, not to external, uncontrollable factors, and are thus said to have an internal locus of control. An internal locus of control is a positive personality trait and has been thoroughly studied in applied psychology, but has not been widely examined in neuroscience. In the present study, correlations between locus of control assessment scores and brain volumes were examined in 777 healthy young adults using magnetic resonance imaging. A whole-brain multiple regression analysis with corrections for the effects of age, gender, and intelligence was conducted. Voxel-based morphometry analyses revealed that gray matter volumes in the anterior cingulate cortex, striatum, and anterior insula positively correlated with higher scores, which indicate an internal LOC. In addition, white matter volumes in the striatum showed significant correlations with an internal locus of control. These results suggest that cognitive, socioemotional, self-regulatory, and reward systems might be associated with internal control orientation. The finding of greater volumes in several brain regions in individuals with a stronger internal locus of control indicates that there is a neuroanatomical basis for the belief that one's efforts are rewarded.

  18. Locus equations derived from compensatory articulation.

    PubMed

    Sussman, H M; Fruchter, D; Cable, A

    1995-05-01

    Locus equations are linear regressions of the onset of F2 transitions on their offsets. These functions vowel-normalize the F2 transitions such that they are able to characterize consonantal place categories. The purpose of this research was to determine if compensatory articulation due to bite blocks would alter the normally linear relationship between F2 transition onset and offset frequencies or alter the differential slopes and y intercepts of locus equations as a function of stop place. Six speakers, three male and three female, each produced /bVt/, /dVt/, and /gVt/ tokens for ten vowel contexts under normal and bite block conditions. Extremely linear and practically identical scatterplots were obtained in the two speaking conditions. No adaptation to the bite blocks was found when comparing locus equations derived from the initial versus the final bite block trial. Results are discussed in relation to the "orderly output constraint," which postulates a perceptual function for linearly related F2 transition end points within consonantal place categories.

  19. Bipolar disorder: Evidence for a major locus

    SciTech Connect

    Spence, M.A.; Flodman, P.L.; Sadovnick, A.D.; Ameli, H.

    1995-10-09

    Complex segregation analyses were conducted on families of bipolar I and bipolar II probands to delineate the mode of inheritance. The probands were ascertained from consecutive referrals to the Mood Disorder Service, University Hospital, University of British Columbia and diagnosed by DSM-III-R and Research Diagnostic Criteria. Data were available on over 1,500 first-degree relatives of the 186 Caucasian probands. The purpose of the analyses was to determine if, after correcting for age and birth cohort, there was evidence for a single major locus. Five models were fit to the data using the statistical package SAGE: (1) dominant, (2) recessive, (3) arbitrary mendelian inheritance, (4) environmental, and (5) no major effects. A single dominant, mendelian major locus was the best fitting of these models for the sample of bipolar I and II probands when only bipolar relatives were defined as affected (polygenic inheritance could not be tested). Adding recurrent major depression to the diagnosis {open_quotes}affected{close_quotes} for relatives reduced the evidence for a major locus effect. Our findings support the undertaking of linkage studies and are consistent with the analyses of the National Institutes of Mental Health (NIMH) Collaborative Study data by Rice et al. and Blangero and Elston. 39 refs., 4 tabs.

  20. Using Penelope to assess the correctness of NASA Ada software: A demonstration of formal methods as a counterpart to testing

    NASA Technical Reports Server (NTRS)

    Eichenlaub, Carl T.; Harper, C. Douglas; Hird, Geoffrey

    1993-01-01

    Life-critical applications warrant a higher level of software reliability than has yet been achieved. Since it is not certain that traditional methods alone can provide the required ultra reliability, new methods should be examined as supplements or replacements. This paper describes a mathematical counterpart to the traditional process of empirical testing. ORA's Penelope verification system is demonstrated as a tool for evaluating the correctness of Ada software. Grady Booch's Ada calendar utility package, obtained through NASA, was specified in the Larch/Ada language. Formal verification in the Penelope environment established that many of the package's subprograms met their specifications. In other subprograms, failed attempts at verification revealed several errors that had escaped detection by testing.

  1. The human growth hormone gene is regulated by a multicomponent locus control region

    SciTech Connect

    Jones, B.; Cooke, N.E.; Liebhaber, S.A.; Monks, B.R.

    1995-12-01

    This article describes research involving the five-member human growth hormone (hGH)/chorionic somatomammotropin (hCS) gene cluster and its expression in the placenta. The results indicate that interactions among multiple elements are required to restrict hGH transcription to the pituitary and generate appropriate levels of expression in the mouse genome. In addition, the results suggest a role for shared and unique regulatory sequences in locus control region-mediated expression of the hGH/hCS gene cluster in the pituitary and possibly the placenta. 67 refs., 9 figs.

  2. E-ADA activity in erythrocytes of lambs experimentally infected with Haemonchus contortus and its possible functional correlations with anemia.

    PubMed

    Da Silva, Aleksandro S; Schafer, Andressa S; Aires, Adelina R; Tonin, Alexandre A; Pimentel, Victor C; Oliveira, Camila B; Zanini, Daniela; Schetinger, Maria R C; Lopes, Sonia T A; Leal, Marta L R

    2013-12-01

    The aim of this study was to evaluate the ecto-adenosine deaminase (E-ADA) activity in erythrocytes of lambs experimentally infected with Haemonchus contortus, correlating it with the degrees of anemia of the experimental animals. A total of 14 healthy lambs, with negative fecal exam for parasites, were to carry out the present study. They were divided into two groups, composed by seven animals: Group A represented the healthy animals (uninfected), while in Group B the animals were infected with 15,000 larvae of H. contortus. Blood was drawn on the days 15, 45 and 75 post-infection (PI) in order to perform the hematological analysis, as well as the mensuration of E-ADA activity in erythrocytes. Parasitological stool exam were performed on the same days mentioned above to follow up the evolution of the infection, as well to determine the number of eggs per gram of feces (EPG). On day 15PI, the animals presented negative EPG and there was not significant (P>0.05) difference between groups in relation to E-ADA activity and hematologic parameters. Animals in Group B had positive EPG for helminths on days 45 and 75 PI, accompanied by varying degrees of anemia, when compared to Group A. At the same periods E-ADA activity was significantly (P<0.05) increased in the erythrocytes of animals of Group B when compared with the not-infected ones. Statistically, there was a negative correlation (P<0.01) between activity E-ADA in erythrocytes and hematocrit on days 45 (r = -0.76) and 75 (r = -0.85)PI. Based on these results and in the scientific literature, it is possible to conclude that the E-ADA may participate on mechanisms related with the pathogenesis and host response against anemia caused by H. contortus.

  3. Hierarchical Ada robot programming system (HARPS)- A complete and working telerobot control system based on the NASREM model

    NASA Technical Reports Server (NTRS)

    Leake, Stephen; Green, Tom; Cofer, Sue; Sauerwein, Tim

    1989-01-01

    HARPS is a telerobot control system that can perform some simple but useful tasks. This capability is demonstrated by performing the ORU exchange demonstration. HARPS is based on NASREM (NASA Standard Reference Model). All software is developed in Ada, and the project incorporates a number of different CASE (computer-aided software engineering) tools. NASREM was found to be a valid and useful model for building a telerobot control system. Its hierarchical and distributed structure creates a natural and logical flow for implementing large complex robust control systems. The ability of Ada to create and enforce abstraction enhanced the implementation of such control systems.

  4. Evolution of the Cañadas edifice and its implications for the origin of the Cañadas Caldera (Tenerife, Canary Islands)

    NASA Astrophysics Data System (ADS)

    Ancochea, E.; Huertas, M. J.; Cantagrel, J. M.; Coello, J.; Fúster, J. M.; Arnaud, N.; Ibarrola, E.

    1999-02-01

    The volcano-stratigraphic and geochronologic data presented in this work show that the Tenerife central zone has been occupied during the last 3 Ma by shield or central composite volcanoes which reached more than 3000 m in height. The last volcanic system, the presently active Teide-Pico Viejo Complex began to form approximately 150 ka ago. The first Cañadas Edifice (CE) volcanic activity took place between about 3.5 Ma and 2.7 Ma. The CE-I is formed mainly by basalts, trachybasalts and trachytes. The remains of this phase outcrop in the Cañadas Wall (CW) sectors of La Angostura (3.5-3.0 Ma and 3.0-2.7 Ma), Boca de Tauce (3.0 Ma), and in the bottom of some external radial ravines (3.5 Ma). The position of its main emission center was located in the central part of the CC. The volcano could have reached 3000 m in height. This edifice underwent a partial destruction by failure and flank collapse, forming debris-avalanches during the 2.6-2.3 Ma period. The debris-avalanche deposits can be seen in the most distal zones in the N flank of the CE-I (Tigaiga Breccia). A new volcanic phase, whose deposits overlie the remains of CE-I and the former debris-avalanche deposits, constituted a new volcanic edifice, the CE-II. The dyke directions analysis and the morphological reconstruction suggest that the CE-II center was situated somewhat westward of the CE-I, reaching some 3200 m in height. The CE-II formations are well exposed on the CW, especially at the El Cedro (2.3-2.00 Ma) sector. They are also frequent in the S flank of the edifice (2.25-1.89 Ma) in Tejina (2.5-1.87 Ma) as well as in the Tigaiga massif to the N (2.23 Ma). During the last periods of activity of CE-II, important explosive eruptions took place forming ignimbrites, pyroclastic flows, and fall deposits of trachytic composition. Their ages vary between 1.5 and 1.6 Ma (Adeje ignimbrites, to the W). In the CW, the Upper Ucanca phonolitic Unit (1.4 Ma) could be the last main episode of the CE-II. Afterwards

  5. A gene locus for targeted ectopic gene integration in Zymoseptoria tritici☆

    PubMed Central

    Kilaru, S.; Schuster, M.; Latz, M.; Das Gupta, S.; Steinberg, N.; Fones, H.; Gurr, S.J.; Talbot, N.J.; Steinberg, G.

    2015-01-01

    Understanding the cellular organization and biology of fungal pathogens requires accurate methods for genomic integration of mutant alleles or fluorescent fusion-protein constructs. In Zymoseptoria tritici, this can be achieved by integrating of plasmid DNA randomly into the genome of this wheat pathogen. However, untargeted ectopic integration carries the risk of unwanted side effects, such as altered gene expression, due to targeting regulatory elements, or gene disruption following integration into protein-coding regions of the genome. Here, we establish the succinate dehydrogenase (sdi1) locus as a single “soft-landing” site for targeted ectopic integration of genetic constructs by using a carboxin-resistant sdi1R allele, carrying the point-mutation H267L. We use various green and red fluorescent fusion constructs and show that 97% of all transformants integrate correctly into the sdi1 locus as single copies. We also demonstrate that such integration does not affect the pathogenicity of Z. tritici, and thus the sdi1 locus is a useful tool for virulence analysis in genetically modified Z. tritici strains. Furthermore, we have developed a vector which facilitates yeast recombination cloning and thus allows assembly of multiple overlapping DNA fragments in a single cloning step for high throughput vector and strain generation. PMID:26092798

  6. Lessons learned applying CASE methods/tools to Ada software development projects

    NASA Technical Reports Server (NTRS)

    Blumberg, Maurice H.; Randall, Richard L.

    1993-01-01

    This paper describes the lessons learned from introducing CASE methods/tools into organizations and applying them to actual Ada software development projects. This paper will be useful to any organization planning to introduce a software engineering environment (SEE) or evolving an existing one. It contains management level lessons learned, as well as lessons learned in using specific SEE tools/methods. The experiences presented are from Alpha Test projects established under the STARS (Software Technology for Adaptable and Reliable Systems) project. They reflect the front end efforts by those projects to understand the tools/methods, initial experiences in their introduction and use, and later experiences in the use of specific tools/methods and the introduction of new ones.

  7. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning.

    PubMed

    Aiuti, Alessandro; Slavin, Shimon; Aker, Memet; Ficara, Francesca; Deola, Sara; Mortellaro, Alessandra; Morecki, Shoshana; Andolfi, Grazia; Tabucchi, Antonella; Carlucci, Filippo; Marinello, Enrico; Cattaneo, Federica; Vai, Sergio; Servida, Paolo; Miniero, Roberto; Roncarolo, Maria Grazia; Bordignon, Claudio

    2002-06-28

    Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloablative conditioning. This protocol was used in two patients for whom enzyme replacement therapy was not available, which allowed the effect of gene therapy alone to be evaluated. Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions (including antigen-specific responses), and lower toxic metabolites. Both patients are currently at home and clinically well, with normal growth and development. These results indicate the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID. PMID:12089448

  8. Rdesign: A data dictionary with relational database design capabilities in Ada

    NASA Technical Reports Server (NTRS)

    Lekkos, Anthony A.; Kwok, Teresa Ting-Yin

    1986-01-01

    Data Dictionary is defined to be the set of all data attributes, which describe data objects in terms of their intrinsic attributes, such as name, type, size, format and definition. It is recognized as the data base for the Information Resource Management, to facilitate understanding and communication about the relationship between systems applications and systems data usage and to help assist in achieving data independence by permitting systems applications to access data knowledge of the location or storage characteristics of the data in the system. A research and development effort to use Ada has produced a data dictionary with data base design capabilities. This project supports data specification and analysis and offers a choice of the relational, network, and hierarchical model for logical data based design. It provides a highly integrated set of analysis and design transformation tools which range from templates for data element definition, spreadsheet for defining functional dependencies, normalization, to logical design generator.

  9. Lessons learned in creating spacecraft computer systems: Implications for using Ada (R) for the space station

    NASA Technical Reports Server (NTRS)

    Tomayko, James E.

    1986-01-01

    Twenty-five years of spacecraft onboard computer development have resulted in a better understanding of the requirements for effective, efficient, and fault tolerant flight computer systems. Lessons from eight flight programs (Gemini, Apollo, Skylab, Shuttle, Mariner, Voyager, and Galileo) and three reserach programs (digital fly-by-wire, STAR, and the Unified Data System) are useful in projecting the computer hardware configuration of the Space Station and the ways in which the Ada programming language will enhance the development of the necessary software. The evolution of hardware technology, fault protection methods, and software architectures used in space flight in order to provide insight into the pending development of such items for the Space Station are reviewed.

  10. AdaNET Dynamic Software Inventory (DSI) prototype component acquisition plan

    NASA Technical Reports Server (NTRS)

    Hanley, Lionel

    1989-01-01

    A component acquisition plan contains the information needed to evaluate, select, and acquire software and hardware components necessary for successful completion of the AdaNET Dynamic Software Inventory (DSI) Management System Prototype. This plan will evolve and be applicable to all phases of the DSI prototype development. Resources, budgets, schedules, and organizations related to component acquisition activities are provided. A purpose and description of a software or hardware component which is to be acquired are presented. Since this is a plan for acquisition of all components, this section is not applicable. The procurement activities and events conducted by the acquirer are described and who is responsible is identified, where the activity will be performed, and when the activities will occur for each planned procurement. Acquisition requirements describe the specific requirements and standards to be followed during component acquisition. The activities which will take place during component acquisition are described. A list of abbreviations and acronyms, and a glossary are contained.

  11. Distribution of Isotopic and Environmental Tracers in Groundwater, Northern Ada County, Southwestern Idaho

    USGS Publications Warehouse

    Adkins, Candice B.; Bartolino, James R.

    2010-01-01

    Residents of northern Ada County, Idaho, depend on groundwater for domestic and agricultural uses. The population of this area is growing rapidly and groundwater resources must be understood for future water-resource management. The U.S. Geological Survey, in cooperation with the Idaho Department of Water Resources, used a suite of isotopic and environmental tracers to gain a better understanding of groundwater ages, recharge sources, and flowpaths in northern Ada County. Thirteen wells were sampled between September and October 2009 for field parameters, major anions and cations, nutrients, oxygen and hydrogen isotopes, tritium, radiocarbon, chlorofluorocarbons, and dissolved gasses. Well depths ranged from 30 to 580 feet below land surface. Wells were grouped together based on their depth and geographic location into the following four categories: shallow aquifer, intermediate/deep aquifer, Willow Creek aquifer, and Dry Creek aquifer. Major cations and anions indicated calcium-bicarbonate and sodium-bicarbonate water types in the study area. Oxygen and hydrogen isotopes carried an oxygen-18 excess signature, possibly indicating recharge from evaporated sources or water-rock interactions in the subsurface. Chlorofluorocarbons detected modern (post-1940s) recharge in every well sampled; tritium data indicated modern water (post-1951) in seven, predominantly shallow wells. Nutrient concentrations tended to be greater in wells signaling recent recharge based on groundwater age dating, thus confirming the presence of recent recharge in these wells. Corrected radiocarbon results generated estimated residence times from modern to 5,100 years before present. Residence time tended to increase with depth, as confirmed by all three age-tracers. The disagreement among residence times indicates that samples were well-mixed and that the sampled aquifers contain a mixture of young and old recharge. Due to a lack of data, no conclusions about sources of recharge could be drawn

  12. Effects of ADA and ADM when Utilized in the Measure of Educational Need in State School Finance Plans. Occasional Paper #16.

    ERIC Educational Resources Information Center

    McLoone, Eugene P.

    From the 1920s through the 1950s, most states used average daily attendance (ADA) in state equalization plans. Beginning in the middle of the 1950s, many states began to use average daily membership (ADM) in such plans. The essential features of any equalization aid plan are (1) a measure of need (such as ADA or ADM), (2) a measure of wealth or…

  13. When the Americans with Disabilities Act Goes Online: Application of the ADA to the Internet and the Worldwide Web. Position Paper.

    ERIC Educational Resources Information Center

    National Council on Disability, Washington, DC.

    This paper addresses the issue of how the Americans with Disabilities Act (ADA) applies to commercial and other private sector Web sites. Beginning with a brief discussion of the role electronic communication plays in our lives, the paper then considers the placement of the ADA in the context of current technology and of computer usage in the…

  14. Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

    PubMed Central

    Vijayamahantesh; Amit, Ajay; Dikhit, Manas R.; Pandey, Raj K.; Singh, Kuljit; Mishra, Ritesh; Das, V. N. R; Das, Pradeep; Bimal, Sanjiva

    2016-01-01

    Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL. PMID:27186641

  15. Atrial natriuretic peptide in the locus coeruleus and its possible role in the regulation of arterial blood pressure, fluid and electrolyte homeostasis

    SciTech Connect

    Geiger, H.; Sterzel, R.B. ); Bahner, U.; Heidland, A. ); Palkovits, M. )

    1991-01-01

    Atrial natriuretic factor (ANP) is present in neuronal cells of the locus coeruleus and its vicinity in the pontine tegmentum and moderate amount of ANP is detectable in this area by radioimmunoassay. The ANP is known as a neuropeptide which may influence the body salt and water homeostasis and blood pressure by targeting both central and peripheral regulatory mechanisms. Whether this pontine ANP cell group is involved in any of these regulatory mechanisms, the effect of various types of hypertension and experimental alterations in the salt and water balance on ANP levels was measured by radioimmunoassay in the locus coeruleus of rats. Adrenalectomy, as well as aldosterone and dexamethasone treatments failed to alter ANP levels in the locus coeruleus. Reduced ANP levels were measured in spontaneously hypertensive rats, and in diabetes insipidus rats with vasopressin replacement. In contrast to these situations, elevated ANP levels were found in rats with DOCA-salt or 1-Kidney-1-clip hypertension. These data suggest a link between ANP levels in the locus coeruleus and fluid volume homeostasis. Whether this link is causal and connected with the major activity of locus coeruleus neurons needs further information.

  16. Locus of control and psychological distress among the aged.

    PubMed

    Hale, W D; Hedgepeth, B E; Taylor, E B

    A relationship between locus of control and adjustment has been found in many studies of young adults, with externals generally reporting higher levels of psychological distress. However, studies of locus of control and adjustment in the aged have produced conflicting results. This investigation examined the relationship between locus of control and self-reported psychopathology in a sample of 139 residents of a retirement complex. Correlation coefficients were computed for locus of control and each of the nine symptom dimensions of the Brief Symptom Inventory. These analyses were carried out separately for males and for females to determine if locus of control orientation was associated with adjustment for both males and females. Results indicate that locus of control is correlated with self-reported psychopathology for older women but not for older men. These results and those of related investigations are discussed within the context of Rotter's social learning theory.

  17. 77 FR 45962 - Approval and Promulgation of State Implementation Plans: Idaho; Boise-Northern Ada County Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-02

    ... October 28, 2002 (67 FR 65713). The State submitted a second 10-year maintenance plan to EPA on February...-classified'' (56 FR 56746). On January 17, 2002, the State requested EPA redesignate the Northern Ada County... 12866 (58 FR 51735, October 4, 1993); Does not impose an information collection burden under...

  18. 77 FR 46008 - Approval and Promulgation of State Implementation Plans: Idaho; Boise-Northern Ada County Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-02

    ... County Air Quality Maintenance Area; Second 10-Year Carbon Monoxide Maintenance Plan AGENCY... Environmental Quality (IDEQ) submitted the Northern Ada County Air Quality Maintenance Area Second 10-year Carbon Monoxide Maintenance Plan on February 10, 2011. In accordance with the requirements of the...

  19. Law & Psychiatry: Has the ADA Been Reborn as a Tool of Broad Community Change for People With Mental Disabilities?

    PubMed

    Petrila, John

    2014-07-01

    Twenty-five years after enactment of the Americans with Disabilities Act (ADA), the U.S. Justice Department has begun to aggressively use the law to compel states to reform community care of individuals with mental disabilities. In this month's Law & Psychiatry column, the author highlights settlement agreements between Justice and the states of New York and Rhode Island that will produce sweeping changes in housing and employment for thousands of individuals with mental disabilities. Is the ADA's original promise finally being realized? The Americans with Disabilities Act (ADA) was enacted with the hope that it would result in the end of segregation based on disability. That promise has been only partially met. However, two recent settlement agreements between the U.S. Department of Justice and the states of New York and Rhode Island promise sweeping change in housing and employment for thousands of individuals with mental disabilities. This column describes the agreements, which adopt best practices as the foundation for community change and which suggest that the ADA may be reaching its full promise.

  20. Aquifer Tests and Characterization of Transmissivity, Ada-Vamoosa Aquifer on the Osage Reservation, Osage County, Oklahoma, 2006

    USGS Publications Warehouse

    Abbott, Marvin M.; DeHay, Kelli

    2008-01-01

    The Ada-Vamoosa aquifer of northeastern Oklahoma is a sedimentary bedrock aquifer of Pennsylvanian age that crops out over 800 square miles of the Osage Reservation. The Osage Nation needed additional information regarding the production potential of the aquifer to aid them in future development planning. To address this need, the U.S. Geological Survey, in cooperation with the Osage Nation, conducted a study of aquifer properties in the Ada-Vamoosa aquifer. This report presents the results of the aquifer tests from 20 wells in the Ada-Vamoosa aquifer and one well in a minor aquifer east of the Ada-Vamoosa outcrop on the Osage Reservation. Well information for 17 of the 21 wells in this report was obtained from the Indian Health Service. Data collected by the U.S. Geological Survey during this investigation are pumping well data from four domestic wells collected during the summer of 2006. Transmissivity values were calculated from well pumping data or were estimated from specific capacity values depending on the reliability of the data. The estimated transmissivity values are 1.1 to 4.3 times greater than the calculated transmissivity values. The calculated and estimated transmissivity values range from 5 to 1,000 feet squared per day.

  1. HPV16 E6-induced and E6AP-dependent inhibition of the transcriptional coactivator hADA3 in human cervical carcinoma cells.

    PubMed

    Hu, Ying; Ye, Feng; Lu, Weiguo; Hong, Die; Wan, Xiaoyun; Xie, Xing

    2009-03-01

    To determine whether there exists an additional pathway of E6 that is independent of direct P53 degradation and whether hADA3, a transcriptional coactivator, is involved in this process. We investigated the association between E6 and hADA3, as well as E6-associated protein (E6AP) and hADA3, in SiHa cells via RNA interference technique. Our results showed that the expression of hADA3 protein was significantly increased, cellular proliferation was decreased and apoptotic rate was increased in SiHa cells treated by E6 siRNA and E6AP siRNA respectively. Our results suggested that oncoprotein E6 inhibits hADA3 in cervical cancer cells and this process is E6AP-dependent.

  2. The developmental activation of the chicken lysozyme locus in transgenic mice requires the interaction of a subset of enhancer elements with the promoter.

    PubMed Central

    Huber, M C; Jägle, U; Krüger, G; Bonifer, C

    1997-01-01

    The complete chicken lysozyme locus is expressed in a position independent fashion in macrophages of transgenic mice and forms the identical chromatin structure as observed with the endogenous gene in chicken cells. Individual lysozyme cis -regulatory elements reorganize their chromatin structure at different developmental stages. Accordingly, their activities are developmentally regulated, indicating a differential role of these elements in locus activation. We have shown previously that a subset of enhancer elements and the promoter are sufficient to activate transcription of the chicken lysozyme gene at the correct developmental stage. Here, we analyzed to which grade the developmentally controlled chromatin reorganizing capacity of cis -regulatory elements in the 5'-region of the chicken lysozyme locus is dependent on promoter elements, and we examined whether the lysozyme locus carries a dominant chromatin reorganizing element. To this end we generated transgenic mouse lines carrying constructs with a deletion of the lysozyme promoter. Expression of the transgene in macrophages is abolished, however, the chromatin reorganizing ability of the cis -regulatory elements is differentially impaired. Some cis -elements require the interaction with the promoter to stabilize transcription factor complexes detectable as DNase I hypersensitive sites in chromatin, whereas other elements reorganize their chromatin structure autonomously. PMID:9224598

  3. Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation.

    PubMed

    Nützmann, Hans-Wilhelm; Reyes-Dominguez, Yazmid; Scherlach, Kirstin; Schroeckh, Volker; Horn, Fabian; Gacek, Agnieszka; Schümann, Julia; Hertweck, Christian; Strauss, Joseph; Brakhage, Axel A

    2011-08-23

    Sequence analyses of fungal genomes have revealed that the potential of fungi to produce secondary metabolites is greatly underestimated. In fact, most gene clusters coding for the biosynthesis of antibiotics, toxins, or pigments are silent under standard laboratory conditions. Hence, it is one of the major challenges in microbiology to uncover the mechanisms required for pathway activation. Recently, we discovered that intimate physical interaction of the important model fungus Aspergillus nidulans with the soil-dwelling bacterium Streptomyces rapamycinicus specifically activated silent fungal secondary metabolism genes, resulting in the production of the archetypal polyketide orsellinic acid and its derivatives. Here, we report that the streptomycete triggers modification of fungal histones. Deletion analysis of 36 of 40 acetyltransferases, including histone acetyltransferases (HATs) of A. nidulans, demonstrated that the Saga/Ada complex containing the HAT GcnE and the AdaB protein is required for induction of the orsellinic acid gene cluster by the bacterium. We also showed that Saga/Ada plays a major role for specific induction of other biosynthesis gene clusters, such as sterigmatocystin, terrequinone, and penicillin. Chromatin immunoprecipitation showed that the Saga/Ada-dependent increase of histone 3 acetylation at lysine 9 and 14 occurs during interaction of fungus and bacterium. Furthermore, the production of secondary metabolites in A. nidulans is accompanied by a global increase in H3K14 acetylation. Increased H3K9 acetylation, however, was only found within gene clusters. This report provides previously undescribed evidence of Saga/Ada dependent histone acetylation triggered by prokaryotes. PMID:21825172

  4. The cell: locus or object of inquiry?

    PubMed

    Bechtel, William

    2010-09-01

    Research in many fields of biology has been extremely successful in decomposing biological mechanisms to discover their parts and operations. It often remains a significant challenge for scientists to recompose these mechanisms to understand how they function as wholes and interact with the environments around them. This is true of the eukaryotic cell. Although initially identified in nineteenth-century cell theory as the fundamental unit of organisms, researchers soon learned how to decompose it into its organelles and chemical constituents and have been highly successful in understanding how these carry out many operations important to life. The emphasis on decomposition is particularly evident in modern cell biology, which for the most part has viewed the cell as merely a locus of the mechanisms responsible for vital phenomena. The cell, however, is also an integrated system and for some explanatory purposes it is essential to recompose it and understand it as an organized whole. I illustrate both the virtues of decomposition (treating the cell as a locus) and recomposition (treating the cell as an object) with recent work on circadian rhythms. Circadian researchers have both identified critical intracellular operations that maintain endogenous oscillations and have also addressed the integration of cells into multicellular systems in which cells constitute units.

  5. Interallelic complementation at the mouse Mitf locus.

    PubMed Central

    Steingrímsson, Eiríkur; Arnheiter, Heinz; Hallsson, Jón Hallsteinn; Lamoreux, M Lynn; Copeland, Neal G; Jenkins, Nancy A

    2003-01-01

    Mutations at the mouse microphthalmia locus (Mitf) affect the development of different cell types, including melanocytes, retinal pigment epithelial cells of the eye, and osteoclasts. The MITF protein is a member of the MYC supergene family of basic-helix-loop-helix-leucine-zipper (bHLHZip) transcription factors and is known to regulate the expression of cell-specific target genes by binding DNA as homodimer or as heterodimer with related proteins. The many mutations isolated at the locus have different effects on the phenotype and can be arranged in an allelic series in which the phenotypes range from near normal to white microphthalmic animals with osteopetrosis. Previous investigations have shown that certain combinations of Mitf alleles complement each other, resulting in a phenotype more normal than that of each homozygote alone. Here we analyze this interallelic complementation in detail and show that it is limited to one particular allele, Mitf(Mi-white) (Mitf(Mi-wh)), a mutation affecting the DNA-binding domain. Both loss- and gain-of-function mutations are complemented, as are other Mitf mutations affecting the DNA-binding domain. Furthermore, this behavior is not restricted to particular cell types: Both eye development and coat color phenotypes are complemented. Our analysis suggests that Mitf(Mi-wh)-associated interallelic complementation is due to the unique biochemical nature of this mutation. PMID:12586714

  6. Evolution of the mating type locus: insights gained from the dimorphic primary fungal pathogens Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii.

    PubMed

    Fraser, James A; Stajich, Jason E; Tarcha, Eric J; Cole, Garry T; Inglis, Diane O; Sil, Anita; Heitman, Joseph

    2007-04-01

    Sexual reproduction of fungi is governed by the mating type (MAT) locus, a specialized region of the genome encoding key transcriptional regulators that direct regulatory networks to specify cell identity and fate. Knowledge of MAT locus structure and evolution has been considerably advanced in recent years as a result of genomic analyses that enable the definition of MAT locus sequences in many species as well as provide an understanding of the evolutionary plasticity of this unique region of the genome. Here, we extend this analysis to define the mating type locus of three dimorphic primary human fungal pathogens, Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii, using genomic analysis, direct sequencing, and bioinformatics. These studies provide evidence that all three species possess heterothallic bipolar mating type systems, with isolates encoding either a high-mobility-group (HMG) domain or an alpha-box transcriptional regulator. These genes are intact in all loci examined and have not been subject to loss or decay, providing evidence that the loss of fertility upon passage in H. capsulatum is not attributable to mutations at the MAT locus. These findings also suggest that an extant sexual cycle remains to be defined in both Coccidioides species, in accord with population genetic evidence. Based on these MAT sequences, a facile PCR test was developed that allows the mating type to be rapidly ascertained. Finally, these studies highlight the evolutionary forces shaping the MAT locus, revealing examples in which flanking genes have been inverted or subsumed and incorporated into an expanding MAT locus, allowing us to propose an expanded model for the evolution of the MAT locus in the phylum Ascomycota. PMID:17337636

  7. Water quality of the Quaternary and Ada-Vamoosa aquifers on the Osage Reservation, Osage County, Oklahoma, 1997

    USGS Publications Warehouse

    Abbott, Marvin M.

    2000-01-01

    The project was to provide information on the quality of ground water from rural-domestic-water wells within the Osage Reservation and compare the water-quality to proximity to oil wells. About 38,500 oil wells have been drilled in the Reservation since drilling began in 1896. About 1,480 square miles or 64 percent of the Reservation is within a quarter mile of an oil well. The unconfined Quaternary sand aquifer covers about 315 square miles or about 14 percent of the Reservation and the confined Ada-Vamoosa sandstone aquifer covers about 800 square miles or about 35 percent of the Reservation. Fifty-eight percent of the Quaternary aquifer and 69 percent of the outcrop area of the Ada-Vamoosa aquifer are within a quarter mile of an oil well . One hundred twenty domestic ground-water wells were sampled from the Quaternary and Ada-Vamoosa aquifers. Forty-nine percent of the Reservation is underlain by the aquifers. Ground-water quality is good on most of the Reservation, but the use of domestic water-supply wells tend to minimize water-quality problems. Existing water-supply wells commonly are located in areas that produce usable volumes of potable water. Several constituents in samples from the Ada-Vamoosa-aquifer within a quarter mile of an oil well were significantly greater than from the aquifer not near oil wells. The constituents include specific conductance, dissolved solids, sodium, sulfate, chloride, bromide, and silica. These ions are probably derived from brine water. In the Ada-Vamoosa aquifer subgroups, 57 percent of the samples near oil wells and 24 percent of the samples not near oil wells had dissolved-solids concentrations greater than 500 milligrams per liter. The water quality in the Quaternary and Ada-Vamoosa aquifers is similar in areas where no oil wells have been drilled but is significantly different for several constituents. Median concentrations of major constituents from the Ada-Vamoosa aquifer not near oil wells were less than or equal to

  8. Data set for comparison of cellular dynamics between human AAVS1 locus-modified and wild-type cells

    PubMed Central

    Mizutani, Takeomi; Haga, Hisashi; Kawabata, Kazushige

    2016-01-01

    This data article describes cellular dynamics, such as migration speed and mobility of the cytoskeletal protein, of wild-type human fibroblast cells and cells with a modified adeno-associated virus integration site 1 (AAVS1) locus on human chromosome 19. Insertion of exogenous gene into the AAVS1 locus has been conducted in recent biological researches. Previously, our data showed that the AAVS1-modification changes cellular contractile force (Mizutani et al., 2015 [1]). To assess if this AAVS1-modification affects cell migration, we compared cellular migration speed and turnover of cytoskeletal protein in human fibroblasts and fibroblasts with a green fluorescent protein gene knocked-in at the AAVS1 locus in this data article. Cell nuclei were stained and changes in their position attributable to cell migration were analyzed. Fluorescence recovery was observed after photobleaching for the fluorescent protein-tagged myosin regulatory light chain. Data here are related to the research article “Transgene Integration into the Human AAVS1 Locus Enhances Myosin II-Dependent Contractile Force by Reducing Expression of Myosin Binding Subunit 85” [1]. PMID:26937449

  9. ABI3 controls embryo degreening through Mendel's I locus

    PubMed Central

    Delmas, Frédéric; Sankaranarayanan, Subramanian; Deb, Srijani; Widdup, Ellen; Bournonville, Céline; Bollier, Norbert; Northey, Julian G. B.; McCourt, Peter; Samuel, Marcus A.

    2013-01-01

    Chlorophyll (chl) is essential for light capture and is the starting point that provides the energy for photosynthesis and thus plant growth. Obviously, for this reason, retention of the green chlorophyll pigment is considered a desirable crop trait. However, the presence of chlorophyll in mature seeds can be an undesirable trait that can affect seed maturation, seed oil quality, and meal quality. Occurrence of mature green seeds in oil crops such as canola and soybean due to unfavorable weather conditions during seed maturity is known to cause severe losses in revenue. One recently identified candidate that controls the chlorophyll degradation machinery is the stay-green gene, SGR1 that was mapped to Mendel’s I locus responsible for cotyledon color (yellow versus green) in peas. A defect in SGR1 leads to leaf stay-green phenotypes in Arabidopsis and rice, but the role of SGR1 in seed degreening and the signaling machinery that converges on SGR1 have remained elusive. To decipher the gene regulatory network that controls degreening in Arabidopsis, we have used an embryo stay-green mutant to demonstrate that embryo degreening is achieved by the SGR family and that this whole process is regulated by the phytohormone abscisic acid (ABA) through ABSCISIC ACID INSENSITIVE 3 (ABI3); a B3 domain transcription factor that has a highly conserved and essential role in seed maturation, conferring desiccation tolerance. Misexpression of ABI3 was sufficient to rescue cold-induced green seed phenotype in Arabidopsis. This finding reveals a mechanistic role for ABI3 during seed degreening and thus targeting of this pathway could provide a solution to the green seed problem in various oil-seed crops. PMID:24043799

  10. Externality and Locus of Control in Obese Children.

    ERIC Educational Resources Information Center

    Isbitsky, Joyce Renee; White, Donna Romano

    1981-01-01

    Significant sex differences indicated that boys generally ate more than girls and held more internal locus of control expectancies. However, obese and normal-weighted children were not differentiated by their performance on either food-related measures nor by their locus of control expectancies. (Author/MP)

  11. Anxiety, locus of control and appraisal of air pollution

    SciTech Connect

    Navarro, P.L.; Simpson-Housley, P.; de Man, A.F.

    1987-06-01

    100 residents of Santiago de Chile took part in a study of the relationship among locus of control, trait-anxiety, and perception of air pollution. Concern over the problem of atmospheric pollution and number of antipollution measures taken was related to trait-anxiety. Locus of control was associated with variation in awareness of pollution hazard.

  12. Locus of Control in Underachieving and Achieving Gifted Students.

    ERIC Educational Resources Information Center

    McClelland, Robert; And Others

    1991-01-01

    This study, with 87 underachieving and 77 achieving gifted students in grades 6-9, found that general locus of control measures did not differentiate between the 2 groups, that both scored significantly higher on positive internal than on negative internal locus of control, and that there were no gender or grade effects. (Author/DB)

  13. Locus of Control and Marital Stability: A Longitudinal Study.

    ERIC Educational Resources Information Center

    Constantine, John A.; Bahr, Stephen J.

    1980-01-01

    Investigated relationship between locus of control and marital stability of young men. Factors derived from locus of control measures included leadership, personal, and fate scales. Results indicated the only significant difference was on the leadership scale between men remaining married and those who did not. (RC)

  14. Personality and Locus of Control among School Children

    ERIC Educational Resources Information Center

    Pandya, Archana A.; Jogsan, Yogesh A.

    2013-01-01

    The main purpose of this investigation is to find out the sex differences in personality traits and locus of control among school children. A total 60 children (30 boys and 30 girls) were taken as a sample. The research tool for personality, children personality questionnaire was used, which was made by Cattell and Porter. Locus of control was…

  15. 40 CFR 798.5200 - Mouse visible specific locus test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... result, one of which is a statistically significant dose-related increase in the number of specific locus... a statistically significant dose-related increase in the number of specific locus mutations or a... eukaryotes which are the carriers of the genetic information for the species. (c) Reference......

  16. The Cajal Body and Histone Locus Body

    PubMed Central

    Nizami, Zehra; Deryusheva, Svetlana; Gall, Joseph G.

    2010-01-01

    The Cajal body (CB) is a nuclear organelle present in all eukaryotes that have been carefully studied. It is identified by the signature protein coilin and by CB-specific RNAs (scaRNAs). CBs contain high concentrations of splicing small nuclear ribonucleoproteins (snRNPs) and other RNA processing factors, suggesting that they are sites for assembly and/or posttranscriptional modification of the splicing machinery of the nucleus. The histone locus body (HLB) contains factors required for processing histone pre-mRNAs. As its name implies, the HLB is associated with the genes that code for histones, suggesting that it may function to concentrate processing factors at their site of action. CBs and HLBs are present throughout the interphase of the cell cycle, but disappear during mitosis. The biogenesis of CBs shows the features of a self-organizing structure. PMID:20504965

  17. Identifying a novel locus for psoriatic arthritis

    PubMed Central

    Budu-Aggrey, Ashley; Bowes, John

    2016-01-01

    A number of studies have identified genetic risk loci for PsA, the majority of which also confer risk for psoriasis. The stronger heritability of PsA in comparison with psoriasis suggests that there should be risk loci that are specific for PsA. Identifying such loci could potentially inform therapy development to provide more effective treatments for PsA patients, especially with a considerable proportion being non-responsive to current therapies. Evidence of a PsA-specific locus has been previously found at HLA-B27 within the MHC region. A recent study has provided evidence of non-HLA risk loci that are specific for PsA at IL23R, PTPN22 and on chromosome 5q31. Functional characterization of these loci will provide further understanding of the pathways underlying PsA, and enable us to apply genetic findings for patient benefit. PMID:26255310

  18. Software architecture for a distributed real-time system in Ada, with application to telerobotics

    NASA Technical Reports Server (NTRS)

    Olsen, Douglas R.; Messiora, Steve; Leake, Stephen

    1992-01-01

    The architecture structure and software design methodology presented is described in the context of telerobotic application in Ada, specifically the Engineering Test Bed (ETB), which was developed to support the Flight Telerobotic Servicer (FTS) Program at GSFC. However, the nature of the architecture is such that it has applications to any multiprocessor distributed real-time system. The ETB architecture, which is a derivation of the NASA/NBS Standard Reference Model (NASREM), defines a hierarchy for representing a telerobot system. Within this hierarchy, a module is a logical entity consisting of the software associated with a set of related hardware components in the robot system. A module is comprised of submodules, which are cyclically executing processes that each perform a specific set of functions. The submodules in a module can run on separate processors. The submodules in the system communicate via command/status (C/S) interface channels, which are used to send commands down and relay status back up the system hierarchy. Submodules also communicate via setpoint data links, which are used to transfer control data from one submodule to another. A submodule invokes submodule algorithms (SMA's) to perform algorithmic operations. Data that describe or models a physical component of the system are stored as objects in the World Model (WM). The WM is a system-wide distributed database that is accessible to submodules in all modules of the system for creating, reading, and writing objects.

  19. Classification of patterns for diffuse lung diseases in thoracic CT images by AdaBoost algorithm

    NASA Astrophysics Data System (ADS)

    Kuwahara, Masayuki; Kido, Shoji; Shouno, Hayaru

    2009-02-01

    CT images are considered as effective for differential diagnosis of diffuse lung diseases. However, the diagnosis of diffuse lung diseases is a difficult problem for the radiologists, because they show a variety of patterns on CT images. So, our purpose is to construct a computer-aided diagnosis (CAD) system for classification of patterns for diffuse lung diseases in thoracic CT images, which gives both quantitative and objective information as a second opinion, to decrease the burdens of radiologists. In this article, we propose a CAD system based on the conventional pattern recognition framework, which consists of two sub-systems; one is feature extraction part and the other is classification part. In the feature extraction part, we adopted a Gabor filter, which can extract patterns such like local edges and segments from input textures, as a feature extraction of CT images. In the recognition part, we used a boosting method. Boosting is a kind of voting method by several classifiers to improve decision precision. We applied AdaBoost algorithm for boosting method. At first, we evaluated each boosting component classifier, and we confirmed they had not enough performances in classification of patterns for diffuse lung diseases. Next, we evaluated the performance of boosting method. As a result, by use of our system, we could improve the classification rate of patterns for diffuse lung diseases.

  20. Fusion of Optimized Indicators from Advanced Driver Assistance Systems (ADAS) for Driver Drowsiness Detection

    PubMed Central

    Daza, Iván G.; Bergasa, Luis M.; Bronte, Sebastián; Yebes, J. Javier; Almazán, Javier; Arroyo, Roberto

    2014-01-01

    This paper presents a non-intrusive approach for monitoring driver drowsiness using the fusion of several optimized indicators based on driver physical and driving performance measures, obtained from ADAS (Advanced Driver Assistant Systems) in simulated conditions. The paper is focused on real-time drowsiness detection technology rather than on long-term sleep/awake regulation prediction technology. We have developed our own vision system in order to obtain robust and optimized driver indicators able to be used in simulators and future real environments. These indicators are principally based on driver physical and driving performance skills. The fusion of several indicators, proposed in the literature, is evaluated using a neural network and a stochastic optimization method to obtain the best combination. We propose a new method for ground-truth generation based on a supervised Karolinska Sleepiness Scale (KSS). An extensive evaluation of indicators, derived from trials over a third generation simulator with several test subjects during different driving sessions, was performed. The main conclusions about the performance of single indicators and the best combinations of them are included, as well as the future works derived from this study. PMID:24412904

  1. Fusion of optimized indicators from Advanced Driver Assistance Systems (ADAS) for driver drowsiness detection.

    PubMed

    Daza, Iván García; Bergasa, Luis Miguel; Bronte, Sebastián; Yebes, Jose Javier; Almazán, Javier; Arroyo, Roberto

    2014-01-09

    This paper presents a non-intrusive approach for monitoring driver drowsiness using the fusion of several optimized indicators based on driver physical and driving performance measures, obtained from ADAS (Advanced Driver Assistant Systems) in simulated conditions. The paper is focused on real-time drowsiness detection technology rather than on long-term sleep/awake regulation prediction technology. We have developed our own vision system in order to obtain robust and optimized driver indicators able to be used in simulators and future real environments. These indicators are principally based on driver physical and driving performance skills. The fusion of several indicators, proposed in the literature, is evaluated using a neural network and a stochastic optimization method to obtain the best combination. We propose a new method for ground-truth generation based on a supervised Karolinska Sleepiness Scale (KSS). An extensive evaluation of indicators, derived from trials over a third generation simulator with several test subjects during different driving sessions, was performed. The main conclusions about the performance of single indicators and the best combinations of them are included, as well as the future works derived from this study.

  2. Stream channel cross sections for a reach of the Boise River in Ada County, Idaho

    USGS Publications Warehouse

    Hortness, Jon E.; Werner, Douglas C.

    1999-01-01

    The Federal Emergency Management Agency produces maps of areas that are likely to be inundated during major floods, usually the 100-year, or 1-percent probability, flood. The maps, called Flood Insurance Rate Maps, are used to determine flood insurance rates for homes, businesses, or other structures located in flood-prone areas. State and local governments also use these maps for help with, among other things, development planning and disaster mitigation. During the period October 1997 through December 1998, the initial phase of a hydraulic analysis project of the Boise River from Barber Dam to the Ada/Canyon County boundary, the U.S. Geological Survey collected stream channel cross-section data at 238 locations along the river and documented 108 elevation reference marks established for horizontal and vertical control. In the final phase of the project, the Survey will use these data to determine water-surface elevations for the 10-, 50-, 100-, and 500-year floods and to define floodway limits. The Federal Emergency Management Agency will use the results of this hydraulic analysis to update the 100- and 500-year flood boundaries and the floodway limits on their Flood Insurance Rate Maps.

  3. Conformational flexibility and subunit arrangement of the modular yeast Spt-Ada-Gcn5 acetyltransferase complex.

    PubMed

    Setiaputra, Dheva; Ross, James D; Lu, Shan; Cheng, Derrick T; Dong, Meng-Qiu; Yip, Calvin K

    2015-04-17

    The Spt-Ada-Gcn5 acetyltransferase (SAGA) complex is a highly conserved, 19-subunit histone acetyltransferase complex that activates transcription through acetylation and deubiquitination of nucleosomal histones in Saccharomyces cerevisiae. Because SAGA has been shown to display conformational variability, we applied gradient fixation to stabilize purified SAGA and systematically analyzed this flexibility using single-particle EM. Our two- and three-dimensional studies show that SAGA adopts three major conformations, and mutations of specific subunits affect the distribution among these. We also located the four functional modules of SAGA using electron microscopy-based labeling and transcriptional activator binding analyses and show that the acetyltransferase module is localized in the most mobile region of the complex. We further comprehensively mapped the subunit interconnectivity of SAGA using cross-linking mass spectrometry, revealing that the Spt and Taf subunits form the structural core of the complex. These results provide the necessary restraints for us to generate a model of the spatial arrangement of all SAGA subunits. According to this model, the chromatin-binding domains of SAGA are all clustered in one face of the complex that is highly flexible. Our results relate information of overall SAGA structure with detailed subunit level interactions, improving our understanding of its architecture and flexibility.

  4. The Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex in Aspergillus nidulans.

    PubMed

    Georgakopoulos, Paraskevi; Lockington, Robin A; Kelly, Joan M

    2013-01-01

    A mutation screen in Aspergillus nidulans uncovered mutations in the acdX gene that led to altered repression by acetate, but not by glucose. AcdX of A. nidulans is highly conserved with Spt8p of Saccharomyces cerevisiae, and since Spt8p is a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex, the SAGA complex may have a role in acetate repression in A. nidulans. We used a bioinformatic approach to identify genes encoding most members of the SAGA complex in A. nidulans, and a proteomic analysis to confirm that most protein components identified indeed exist as a complex in A. nidulans. No apparent compositional differences were detected in mycelia cultured in acetate compared to glucose medium. The methods used revealed apparent differences between Yeast and A. nidulans in the deubiquitination (DUB) module of the complex, which in S. cerevisiae consists of Sgf11p, Sus1p, and Ubp8p. Although a convincing homologue of S. cerevisiae Ubp8p was identified in the A. nidulans genome, there were no apparent homologues for Sus1p and Sgf11p. In addition, when the SAGA complex was purified from A. nidulans, members of the DUB module were not co-purified with the complex, indicating that functional homologues of Sus1p and Sgf11p were not part of the complex. Thus, deubiquitination of H2B-Ub in stress conditions is likely to be regulated differently in A. nidulans compared to S. cerevisiae.

  5. Locus of Control Orientation: Parents, Peers, and Place.

    PubMed

    Ahlin, Eileen M; Lobo Antunes, Maria João

    2015-09-01

    An internal locus of control contributes to positive youth outcomes such as a general well-being and academic success, while also serving as a protective factor against exposure to community violence and reducing negative behaviors like violence. Despite these benefits, very little is known about antecedents of an internal locus of control orientation. Without an understanding of what factors contribute to the development of an internal locus of control, it is not clear how to best encourage its formation. This study uses data from the Project on Human Development in Chicago Neighborhoods to examine whether various mesosystem variables (family management strategies, peer interactions, neighborhood context, and individual-level characteristics) are associated with an internal locus of control orientation among 1,076 youth ages 9-19 living in 78 Chicago neighborhoods. Study participants were Hispanic (46 %), African American (34 %), and White (15 %), and 50 % were female. The findings suggest that, while most levels of the mesosystem influence locus of control orientation, family management strategies are more prominent determinants of an internal locus of control than peers, neighborhood context, or individual characteristics. Parental supervision over the time a youth spends at home and family socioeconomic status are consistent predictors of an internal locus of control, while harsh discipline is associated with an external locus of control. The discussion examines the import of various parenting techniques in shaping an internal locus of control and considers future avenues for research to further unpack how antecedents of locus of control can vary across youth. PMID:25617000

  6. Locus of Control Orientation: Parents, Peers, and Place.

    PubMed

    Ahlin, Eileen M; Lobo Antunes, Maria João

    2015-09-01

    An internal locus of control contributes to positive youth outcomes such as a general well-being and academic success, while also serving as a protective factor against exposure to community violence and reducing negative behaviors like violence. Despite these benefits, very little is known about antecedents of an internal locus of control orientation. Without an understanding of what factors contribute to the development of an internal locus of control, it is not clear how to best encourage its formation. This study uses data from the Project on Human Development in Chicago Neighborhoods to examine whether various mesosystem variables (family management strategies, peer interactions, neighborhood context, and individual-level characteristics) are associated with an internal locus of control orientation among 1,076 youth ages 9-19 living in 78 Chicago neighborhoods. Study participants were Hispanic (46 %), African American (34 %), and White (15 %), and 50 % were female. The findings suggest that, while most levels of the mesosystem influence locus of control orientation, family management strategies are more prominent determinants of an internal locus of control than peers, neighborhood context, or individual characteristics. Parental supervision over the time a youth spends at home and family socioeconomic status are consistent predictors of an internal locus of control, while harsh discipline is associated with an external locus of control. The discussion examines the import of various parenting techniques in shaping an internal locus of control and considers future avenues for research to further unpack how antecedents of locus of control can vary across youth.

  7. The SANT domain of Ada2 is required for normal acetylation of histones by the yeast SAGA complex.

    PubMed

    Sterner, David E; Wang, Xun; Bloom, Melissa H; Simon, Gabriel M; Berger, Shelley L

    2002-03-01

    Transcription is regulated through chromatin remodeling and histone modification, mediated by large protein complexes. Histone and nucleosome interaction has been shown to be mediated by specific chromatin domains called bromodomains and chromodomains. Here we provide evidence for a similar function of two additional domains within the yeast SAGA complex, containing the histone acetyltransferase Gcn5. We have analyzed deletion and substitution mutations within Gcn5 and Ada2, an interacting protein within SAGA, and have identified substrate recognition functions within the SANT domain of Ada2 and regions of the histone acetyltransferase domain of Gcn5 that are distinct from catalytic function itself. These results suggest that histone and nucleosomal substrate recognition by SAGA involves multiple conserved domains and proteins, beyond those that have been previously identified. PMID:11777910

  8. Using naturalistic driving films as a design tool for investigating driver requirements in HMI design for ADAS.

    PubMed

    Wang, Minjuan; Sun, Dong; Chen, Fang

    2012-01-01

    In recent years, there are many naturalistic driving projects have been conducted, such as the 100-Car Project (Naturalistic Driving study in United State), EuroFOT(European Large-Scale Field Operational Tests on Vehicle Systems), SeMi- FOT(Sweden Michigan Naturalistic Field Operational Test and etc. However, those valuable naturalistic driving data hasn't been applied into Human-machine Interaction (HMI) design for Advanced Driver Assistance Systems (ADAS), a good HMI design for ADAS requires a deep understanding of drive environment and the interactions between the driving car and other road users in different situations. The results demonstrated the benefits of using naturalistic driving films as a mean for enhancing focus group discussion for better understanding driver's needs and traffic environment constraints. It provided an efficient tool for designers to have inside knowledge about drive and the needs for information presentation; The recommendations for how to apply this method is discussed in the paper.

  9. HMGB1 binds to the rs7903146 locus in TCF7L2 in human pancreatic islets.

    PubMed

    Zhou, Yuedan; Oskolkov, Nikolay; Shcherbina, Liliya; Ratti, Joyce; Kock, Kian-Hong; Su, Jing; Martin, Brian; Oskolkova, Malin Zackrisson; Göransson, Olga; Bacon, Julie; Li, Weimin; Bucciarelli, Saskia; Cilio, Corrado; Brazma, Alvis; Thatcher, Bradley; Rung, Johan; Wierup, Nils; Renström, Erik; Groop, Leif; Hansson, Ola

    2016-07-15

    The intronic SNP rs7903146 in the T-cell factor 7-like 2 gene (TCF7L2) is the common genetic variant most highly associated with Type 2 diabetes known to date. The risk T-allele is located in an open chromatin region specific to human pancreatic islets of Langerhans, thereby accessible for binding of regulatory proteins. The risk T-allele locus exhibits stronger enhancer activity compared to the non-risk C-allele. The aim of this study was to identify transcriptional regulators that bind the open chromatin region in the rs7903146 locus and thereby potentially regulate TCF7L2 expression and activity. Using affinity chromatography followed by Edman sequencing, we identified one candidate regulatory protein, i.e. high-mobility group protein B1 (HMGB1). The binding of HMGB1 to the rs7903146 locus was confirmed in pancreatic islets from human deceased donors, in HCT116 and in HEK293 cell lines using: (i) protein purification on affinity columns followed by Western blot, (ii) chromatin immunoprecipitation followed by qPCR and (iii) electrophoretic mobility shift assay. The results also suggested that HMGB1 might have higher binding affinity to the C-allele of rs7903146 compared to the T-allele, which was supported in vitro using Dynamic Light Scattering, possibly in a tissue-specific manner. The functional consequence of HMGB1 depletion in HCT116 and INS1 cells was reduced insulin and TCF7L2 mRNA expression, TCF7L2 transcriptional activity and glucose stimulated insulin secretion. These findings suggest that the rs7903146 locus might exert its enhancer function by interacting with HMGB1 in an allele dependent manner. PMID:26845344

  10. Study of the Alsys implementation of the Catalogue of Interface Features and Options for the Ada language for 80386 Unix

    NASA Technical Reports Server (NTRS)

    Gibson, James S.; Barnes, Michael J.; Ostermiller, Daniel L.

    1993-01-01

    A set of programs was written to test the functionality and performance of the Alsys Ada implementation of the Catalogue of Interface Features and Options (CIFO), a set of optional Ada packages for real-time applications. No problems were found with the task id, preemption control, or shared-data packages. Minor problems were found with the dispatching control, dynamic priority, events, non-waiting entry call, semaphore, and scheduling packages. The Alsys implementation is derived mostly from Release 2 of the CIFO standard, but includes some of the features of Release 3 and some modifications unique to Alsys. Performance measurements show that the semaphore and shared-data features are an order-of-magnitude faster than the same mechanisms using an Ada rendezvous. The non-waiting entry call is slightly faster than a standard rendezvous. The existence of errors in the implementation, the incompleteness of the documentation from the published standard impair the usefulness of this implementation. Despite those short-comings, the Alsys CIFO implementation might be of value in the development of real-time applications.

  11. Using vertical electrical soundings for characterizing hydrogeological and tectonic settings in Deir El-Adas area, Yarmouk Basin, Syria

    NASA Astrophysics Data System (ADS)

    Al-Fares, Walid

    2016-06-01

    The present study is aimed at characterizing the subsurface geological and tectonic structure in Deir El-Adas area, by using Vertical Electrical Sounding survey (VES) and hydrogeological investigations, in order to determine the causes of the failure for the majority of the wells drilled in the area. The survey data was treated in three different approaches including direct VES inversion, pseudo-2D method and horizontal profiling, in order to maximize the reliability of the data interpretation. The results revealed the presence of a local faulted anticline structure at the top of the Paleogene formation, underneath the basaltic outcrops where Deir El-Adas village is situated. The appearance of this subsurface anticline structure has complicated the local hydrogeological situation, and most likely led to limitation of the groundwater recharge in the area. Moreover, the performed piezometric and discharge maps indicated the presence of a notable groundwater watershed, in addition to feeble water productivity of the wells drilled adjacent to Deir El-Adas, mostly related to the subsurface geological and tectonic settings in the area.

  12. Low Cost Upper Atmosphere Sounder (LOCUS)

    NASA Astrophysics Data System (ADS)

    Gerber, Daniel; Swinyard, Bruce M.; Ellison, Brian N.; Aylward, Alan D.; Aruliah, Anasuya; Plane, John M. C.; Feng, Wuhu; Saunders, Christopher; Friend, Jonathan; Bird, Rachel; Linfield, Edmund H.; Davies, A. Giles; Parkes, Steve

    2014-05-01

    near future. We describe the current instrument configuration of LOCUS, and give a first preview of the expected science return such a mission would yield. The LOCUS instrument concept calls for four spectral bands, a first band at 4.7 THz to target atomic oxygen (O), a second band at 3.5 THz to target hydroxyl (OH), a third band at 1.1 THz to cover several diatomic species (NO, CO, O3, H2O) and finally a fourth band at 0.8 THz to retrieve pointing information from molecular oxygen (O2). LOCUS would be the first satellite instrument to measure atomic oxygen on a global scale with a precision that will allow the retrieval of the global O distribution. It would also be the first time that annual and diurnal changes in O are measured. This will be a significant step forward in understanding the chemistry and dynamics of the MLT. Current indications (derived from CRISTA measurement) lead us to believe that current models only give a poor representation of upper atmospheric O. The secondary target species can help us to address additional scientific questions related to both Climate (distribution of climate relevant gases, highly geared cooling of the MLT in response to Climate change, increased occurrence of Polar Mesospheric Clouds (PMC), etc) and Space Weather (precipitation of electrically charged particles and impact on NOx chemistry, fluctuations of solar Lyman-alpha flux through shown in the the distribution of photochemically active species, etc).

  13. Dynamic chromatin: the regulatory domain organization of eukaryotic gene loci.

    PubMed

    Bonifer, C; Hecht, A; Saueressig, H; Winter, D M; Sippel, A E

    1991-10-01

    It is hypothesized that nuclear DNA is organized in topologically constrained loop domains defining basic units of higher order chromatin structure. Our studies are performed in order to investigate the functional relevance of this structural subdivision of eukaryotic chromatin for the control of gene expression. We used the chicken lysozyme gene locus as a model to examine the relation between chromatin structure and gene function. Several structural features of the lysozyme locus are known: the extension of the region of general DNAasel sensitivity of the active gene, the location of DNA-sequences with high affinity for the nuclear matrix in vitro, and the position of DNAasel hypersensitive chromatin sites (DHSs). The pattern of DHSs changes depending on the transcriptional status of the gene. Functional studies demonstrated that DHSs mark the position of cis-acting regulatory elements. Additionally, we discovered a novel cis-activity of the border regions of the DNAasel sensitive domain (A-elements). By eliminating the position effect on gene expression usually observed when genes are randomly integrated into the genome after transfection, A-elements possibly serve as punctuation marks for a regulatory chromatin domain. Experiments using transgenic mice confirmed that the complete structurally defined lysozyme gene domain behaves as an independent regulatory unit, expressing the gene in a tissue specific and position independent manner. These expression features were lost in transgenic mice carrying a construct, in which the A-elements as well as an upstream enhancer region were deleted, indicating the lack of a locus activation function on this construct. Experiments are designed in order to uncover possible hierarchical relationships between the different cis-acting regulatory elements for stepwise gene activation during cell differentiation. We are aiming at the definition of the basic structural and functional requirements for position independent and high

  14. Dynamic chromatin: the regulatory domain organization of eukaryotic gene loci.

    PubMed

    Bonifer, C; Hecht, A; Saueressig, H; Winter, D M; Sippel, A E

    1991-10-01

    It is hypothesized that nuclear DNA is organized in topologically constrained loop domains defining basic units of higher order chromatin structure. Our studies are performed in order to investigate the functional relevance of this structural subdivision of eukaryotic chromatin for the control of gene expression. We used the chicken lysozyme gene locus as a model to examine the relation between chromatin structure and gene function. Several structural features of the lysozyme locus are known: the extension of the region of general DNAasel sensitivity of the active gene, the location of DNA-sequences with high affinity for the nuclear matrix in vitro, and the position of DNAasel hypersensitive chromatin sites (DHSs). The pattern of DHSs changes depending on the transcriptional status of the gene. Functional studies demonstrated that DHSs mark the position of cis-acting regulatory elements. Additionally, we discovered a novel cis-activity of the border regions of the DNAasel sensitive domain (A-elements). By eliminating the position effect on gene expression usually observed when genes are randomly integrated into the genome after transfection, A-elements possibly serve as punctuation marks for a regulatory chromatin domain. Experiments using transgenic mice confirmed that the complete structurally defined lysozyme gene domain behaves as an independent regulatory unit, expressing the gene in a tissue specific and position independent manner. These expression features were lost in transgenic mice carrying a construct, in which the A-elements as well as an upstream enhancer region were deleted, indicating the lack of a locus activation function on this construct. Experiments are designed in order to uncover possible hierarchical relationships between the different cis-acting regulatory elements for stepwise gene activation during cell differentiation. We are aiming at the definition of the basic structural and functional requirements for position independent and high

  15. Genomic organization of the S-locus region of Brassica.

    PubMed

    Shiba, Hiroshi; Kenmochi, Masayuki; Sugihara, Minoru; Iwano, Megumi; Kawasaki, Shinji; Suzuki, Go; Watanabe, Masao; Isogai, Akira; Takayama, Seiji

    2003-03-01

    To gain some insights into the structure of the S-locus and the mechanisms that have kept its diversity, a 75-kb genomic fragment containing the self-incompatibility (S) locus region was isolated from the S12-haplotype of Brassica rapa and compared with those of other S-haplotypes. The region around the S determinant genes was highly polymorphic and filled with S-haplotype-specific intergenic sequences. The diverse genomic structure must contribute to the suppression of recombination at the S-locus.

  16. Distribution and origin of dissolved gases of groundwaters at Las Cañadas aquifer, Tenerife, Canary Islands

    NASA Astrophysics Data System (ADS)

    Marrero, R.; Melian, G.; Padron, E.; Sortino, F.; Hernandez Perez, P. A.; Lopez, D. L.; Perez, N.

    2009-12-01

    Volcanic aquifers commonly trap an important fraction of the main soluble components of fluids released from volcanic-hydrothermal system (CO2, SO2, H2S, HCl, HF, etc.). In particular, the interactions between volcanic gases and volcanic aquifers have been studied through hydrogeochemical parameters, as major and minor ions contents and dissolved gases in groundwaters. In the context of hydrogeochemical studies applied to active volcanic areas, studies of dissolved gases species in groundwater could be a useful tool to better understand the subsurface processes as gas-water-rock interaction or to strengthen the geochemical seismic-volcanic surveillance programs. In this work, we report the results of the geochemical characterization of dissolved gases (N2, O2, Ar, CO2, CH4, CO, H2, He, 222Rn, δ13CTDIC) in 96 groundwater samples from Las Cañadas aquifer (around Teide volcano) between May and October, 2006. The main aims of this work are: (1) to determine the background level of magmatic gas input in the aquifer during quiescent periods, (2) to better define the origin of dissolved gases in Las Cañadas aquifer, specially CO2, (3) to evaluate the gas-water-rock interaction processes occurring at depth, and (4) to delineate high permeable pathway of upward migration of volcanic-hydrothermal gases. In general, the dissolved gas phase in groundwaters of Las Cañadas aquifer is relatively enriched in endogenous gases (CO2, He and H2) while it is relatively depleted in atmospheric gases (N2, O2 and Ar). N2-O2-CO2 triangular diagram shows that dissolved gases in most of analyzed groundwater are variable mixtures of CO2-rich fluids from the volcanic-hydrothermal system (as represent the Teide fumaroles) with dissolved air. The relatively high N2/O2 ratio in some groundwater compared to the air saturated water suggests an O2 consumption during gas-water-rock interactions occurring at depth. Spatial distribution maps show anomalous concentration of 222Rn CH4, H2 and CO2

  17. Syzygium cumini is more effective in preventing the increase of erythrocytic ADA activity than phenolic compounds under hyperglycemic conditions in vitro.

    PubMed

    De Bona, Karine S; Bonfanti, Gabriela; Bitencourt, Paula E R; Cargnelutti, Lariane O; da Silva, Priscila S; da Silva, Thainan P; Zanette, Régis A; Pigatto, Aline S; Moretto, Maria B

    2014-06-01

    Syzygium cumini (S. cumini) is a plant known for its antidiabetic properties. The aim of this study was to evaluate the effect of Sc aqueous leaf extract (ASc) on adenosine deaminase (ADA) activity in erythrocytes (RBCs) exposed to high glucose concentrations (30 mM) in vitro. We also investigated the effects of the main phenolic compounds found in ASc (gallic acid, rutin, and chlorogenic acid) and the effects of insulin, caffeine, and dipyridamole, which are substances involved in the adenosine metabolism, on ADA activity in vitro. Blood samples were obtained from healthy volunteers and a suspension of RBCs was used for the determination of ADA activity. The results showed that: (1) the effect of ASc on ADA activity was more significant than the combination of phenolic compounds; (2) insulin, caffeine, or dipyridamole prevented high glucose increase of ADA activity at doses as low as 50 μU/mL, 25 μM, and 1 μM, respectively; (3) the inhibitory effect caused by ASc on erythrocyte ADA activity remained practically the same after the combination of the extract with insulin or caffeine; (4) when RBCs were exposed to ASc plus dipyridamole, this chemical attenuated the effect of ASc on ADA activity, suggesting an antagonism or a competition with ASc by the same site of action. Therefore, ASc was more effective in preventing the increase in ADA activity than phenolic compounds, suggesting that ASc may collaborate to improve endothelial dysfunction, antioxidant, anti-inflammatory, and antithrombotic properties of adenosine by affecting its metabolism. The results of this study help to provide evidence of the empirically supported benefits of the use of S. cumini in diabetes.

  18. Syzygium cumini is more effective in preventing the increase of erythrocytic ADA activity than phenolic compounds under hyperglycemic conditions in vitro.

    PubMed

    De Bona, Karine S; Bonfanti, Gabriela; Bitencourt, Paula E R; Cargnelutti, Lariane O; da Silva, Priscila S; da Silva, Thainan P; Zanette, Régis A; Pigatto, Aline S; Moretto, Maria B

    2014-06-01

    Syzygium cumini (S. cumini) is a plant known for its antidiabetic properties. The aim of this study was to evaluate the effect of Sc aqueous leaf extract (ASc) on adenosine deaminase (ADA) activity in erythrocytes (RBCs) exposed to high glucose concentrations (30 mM) in vitro. We also investigated the effects of the main phenolic compounds found in ASc (gallic acid, rutin, and chlorogenic acid) and the effects of insulin, caffeine, and dipyridamole, which are substances involved in the adenosine metabolism, on ADA activity in vitro. Blood samples were obtained from healthy volunteers and a suspension of RBCs was used for the determination of ADA activity. The results showed that: (1) the effect of ASc on ADA activity was more significant than the combination of phenolic compounds; (2) insulin, caffeine, or dipyridamole prevented high glucose increase of ADA activity at doses as low as 50 μU/mL, 25 μM, and 1 μM, respectively; (3) the inhibitory effect caused by ASc on erythrocyte ADA activity remained practically the same after the combination of the extract with insulin or caffeine; (4) when RBCs were exposed to ASc plus dipyridamole, this chemical attenuated the effect of ASc on ADA activity, suggesting an antagonism or a competition with ASc by the same site of action. Therefore, ASc was more effective in preventing the increase in ADA activity than phenolic compounds, suggesting that ASc may collaborate to improve endothelial dysfunction, antioxidant, anti-inflammatory, and antithrombotic properties of adenosine by affecting its metabolism. The results of this study help to provide evidence of the empirically supported benefits of the use of S. cumini in diabetes. PMID:24407852

  19. New acceptor-donor-acceptor (A-D-A) type copolymers for efficient organic photovoltaic devices

    NASA Astrophysics Data System (ADS)

    Ghomrasni, S.; Ayachi, S.; Alimi, K.

    2015-01-01

    Three new conjugated systems alternating acceptor-donor-acceptor (A-D-A) type copolymers have been investigated by means of Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT) at the 6-31g (d) level of theory. 4,4‧-Dimethoxy-chalcone, also called the 1,3-bis(4-methoxyphenyl)prop-2-en-1-one (BMP), has been used as a common acceptor moiety. It forced intra-molecular S⋯O interactions through alternating oligo-thiophene derivatives: 4-AlkylThiophenes (4-ATP), 4-AlkylBithiophenes (4-ABTP) and 4-Thienylene Vinylene (4-TEV) as donor moieties. The band gap, HOMO and LUMO electron distributions as well as optical properties were analyzed for each molecule. The fully optimized resulting copolymers showed low band gaps (2.2-2.8 eV) and deep HOMO energy levels ranging from -4.66 to -4.86 eV. A broad absorption [300-900 nm] covering the solar spectrum and absorption maxima ranges from 486 to 604 nm. In addition, organic photovoltaic cells (OPCs) based on alternating copolymers in bulk heterojunction (BHJ) composites with the 1-(3-methoxycarbonyl) propyl-1-phenyl-[6,6]-C61 (PCBM), as an acceptor, have been optimized. Thus, the band gap decreased to 1.62 eV, the power conversion efficiencies (PCEs) were about 3-5% and the open circuit voltage Voc of the resulting molecules decreased from 1.50 to 1.27 eV.

  20. Insights into behavioral vulnerability to differential sleep pressure and circadian phase from a functional ADA polymorphism.

    PubMed

    Reichert, Carolin F; Maire, Micheline; Gabel, Virginie; Viola, Antoine U; Kolodyazhniy, Vitaliy; Strobel, Werner; Götz, Thomas; Bachmann, Valérie; Landolt, Hans-Peter; Cajochen, Christian; Schmidt, Christina

    2014-04-01

    Sleep loss affects human behavior in a nonuniform manner, depending on the cognitive domain and also the circadian phase. Besides, evidence exists about stable interindividual variations in sleep loss-related performance impairments. Despite this evidence, only a few studies have considered both circadian phase and neurobehavioral domain when investigating trait-like vulnerability to sleep manipulation. By applying a randomized, crossover design with 2 sleep pressure conditions (40 h sleep deprivation vs. 40 h multiple naps), we investigated the influence of a human adenosine deaminase (ADA) polymorphism (rs73598374) on several behavioral measures throughout nearly 2 circadian cycles. Confirming earlier studies, we observed that under sleep deprivation the previously reported vulnerable G/A-allele carriers felt overall sleepier than G/G-allele carriers. As expected, this difference was no longer present when sleep pressure was reduced by the application of multiple naps. Concomitantly, well-being was worse in the G/A genotype under sleep loss when compared to the nap protocol, and n-back working memory performance appeared to be specifically susceptible to sleep-wake manipulation in this genotype. When considering psychomotor vigilance performance, however, a higher sensitivity to sleep-wake manipulation was detected in homozygous participants, but specifically at the end of the night and only for optimal task performance. Although these data are based on a small sample size and hence require replication (12 G/A- and 12 G/G-allele carriers), they confirm the assumption that interindividual differences regarding the effect of sleep manipulation highly depend on the cognitive task and circadian phase, and thus emphasize the necessity of a multimethodological approach. Moreover, they indicate that napping might be suitable to counteract endogenously heightened sleep pressure depending on the neurobehavioral domain.

  1. THE LOCUS COERULEUS AND CENTRAL CHEMOSENSITIVITY

    PubMed Central

    Gargaglioni, Luciane H.; Hartzler, Lynn K.; Putnam, Robert W.

    2010-01-01

    The locus coeruleus (LC) lies in the dorsal pons and supplies noradrenergic (NA) input to many regions of the brain, including respiratory control areas. The LC may provide tonic input for basal respiratory drive and is involved in central chemosensitivity since focal acidosis of the region stimulates ventilation and ablation reduces CO2-induced increased ventilation. The output of LC is modulated by both serotonergic and glutamatergic inputs. A large percentage of LC neurons are intrinsically activated by hypercapnia. This percentage and the magnitude of their response are highest in young neonates and decrease dramatically after postnatal day P10. The cellular bases for intrinsic chemosensitivity of LC neurons are comprised of multiple factors, primary among them being reduced extracellular and intracellular pH, which inhibit inwardly rectifying and voltage-gated K+ channels, and activate L-type Ca2+ channels. Activation of KCa channels in LC neurons may limit their ultimate response to hypercapnia. Finally, the LC mediates central chemosensitivity and contains pH-sensitive neurons in amphibians, suggesting that the LC has a long-standing phylogenetic role in respiratory control. PMID:20435170

  2. Sequence Variation Within the Fragile X Locus

    PubMed Central

    Mathews, Debra J.; Kashuk, Carl; Brightwell, Gale; Eichler, Evan E.; Chakravarti, Aravinda

    2001-01-01

    The human genome provides a reference sequence, which is a template for resequencing studies that aim to discover and interpret the record of common ancestry that exists in extant genomes. To understand the nature and pattern of variation and linkage disequilibrium comprising this history, we present a study of ∼31 kb spanning an ∼70 kb region of FMR1, sequenced in a sample of 20 humans (worldwide sample) and four great apes (chimp, bonobo, and gorilla). Twenty-five polymorphic sites and two insertion/deletions, distributed in 11 unique haplotypes, were identified among humans. Africans are the only geographic group that do not share any haplotypes with other groups. Parsimony analysis reveals two main clades and suggests that the four major human geographic groups are distributed throughout the phylogenetic tree and within each major clade. An African sample appears to be most closely related to the common ancestor shared with the three other geographic groups. Nucleotide diversity, π, for this sample is 2.63 ± 6.28 × 10−4. The mutation rate, μ, is 6.48 × 10−10 per base pair per year, giving an ancestral population size of ∼6200 and a time to the most recent common ancestor of ∼320,000 ± 72,000 per base pair per year. Linkage disequilibrium (LD) at the FMR1 locus, evaluated by conventional LD analysis and by the length of segment shared between any two chromosomes, is extensive across the region. PMID:11483579

  3. Chromosomal locus for staphylococcal enterotoxin B.

    PubMed Central

    Shafer, W M; Iandolo, J J

    1978-01-01

    The genetic locus of staphylococcal enterotoxin B (SEB) was investigated in the Staphylococcus aureus food-poisoning isolates, strains S6 and 277. Direct neutral sucrose gradient centrifugation analysis of sodium dodecyl sulfate-sodium chloride-mediated cleared lysates demonstrated that strain S6 contained a single 37S plasmid. Transductional analysis revealed that the 37S plasmid in S6 encoded for cadmium resistance (Cad) but not SEB. Additionally, elimination of cadmium resistance in S6 provided a plasmid-negative derivative that produced SEB at the same level as the parent. Examination of strain 277 showed two plasmids, a 37S species encoding for penicillin resistance (Penr) and a 21S species containing the gene(s) responsible for tetracycline resistance (Tetr). Elimination of the 37S, penr plasmid in 277 had no effect on SEB production, whereas introduction of the 21S tetr plasmid via transformation into strain 8325 (SEB--) did not confer enterotoxigenesis upon the transformants. The data obtained in this investigation suggest that the SEB gene(s) in these food-poisoning isolates of S. aureus is chromosomal. Images PMID:669796

  4. Essential Functional Interactions of Saga, a Saccharomyces Cerevisiae Complex of Spt, Ada, and Gcn5 Proteins, with the Snf/Swi and Srb/Mediator Complexes

    PubMed Central

    Roberts, S. M.; Winston, F.

    1997-01-01

    The Saccharomyces cerevisiae transcription factor Spt20/Ada5 was originally identified by mutations that suppress Ty insertion alleles and by mutations that suppress the toxicity caused by Gal4-VP16 overexpression. Here we present evidence for physical associations between Spt20/Ada5 and three other Spt proteins, suggesting that they exist in a complex. A related study demonstrates that this complex also contains the histone acetyltransferase, Gcn5, and Ada2. This complex has been named SAGA (Spt/Ada/Gcn5 acetyltransferase). To identify functions that genetically interact with SAGA, we have screened for mutations that cause lethality in an spt20Δ/ada5Δ mutant. Our screen identified mutations in SNF2, SIN4, and GAL11. These mutations affect two known transcription complexes: Snf/Swi, which functions in nucleosome remodeling, and Srb/mediator, which is required for regulated transcription by RNA polymerase II. Systematic analysis has demonstrated that spt20Δ/ada5Δand spt7Δ mutations cause lethality with every snf/swi and srb/mediator mutation tested. Furthermore, a gcn5Δ mutation causes severe sickness with snf/swi mutations, but not with srb/mediator mutations. These findings suggest that SAGA has multiple activities and plays critical roles in transcription by RNA polymerase II. PMID:9335585

  5. Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant

    PubMed Central

    Almeida, Rodrigo; Ricaño-Ponce, Isis; Kumar, Vinod; Deelen, Patrick; Szperl, Agata; Trynka, Gosia; Gutierrez-Achury, Javier; Kanterakis, Alexandros; Westra, Harm-Jan; Franke, Lude; Swertz, Morris A.; Platteel, Mathieu; Bilbao, Jose Ramon; Barisani, Donatella; Greco, Luigi; Mearin, Luisa; Wolters, Victorien M.; Mulder, Chris; Mazzilli, Maria Cristina; Sood, Ajit; Cukrowska, Bozena; Núñez, Concepción; Pratesi, Riccardo; Withoff, Sebo; Wijmenga, Cisca

    2014-01-01

    Using the Immunochip for genotyping, we identified 39 non-human leukocyte antigen (non-HLA) loci associated to celiac disease (CeD), an immune-mediated disease with a worldwide frequency of ∼1%. The most significant non-HLA signal mapped to the intronic region of 70 kb in the LPP gene. Our aim was to fine map and identify possible functional variants in the LPP locus. We performed a meta-analysis in a cohort of 25 169 individuals from six different populations previously genotyped using Immunochip. Imputation using data from the Genome of the Netherlands and 1000 Genomes projects, followed by meta-analysis, confirmed the strong association signal on the LPP locus (rs2030519, P = 1.79 × 10−49), without any novel associations. The conditional analysis on this top SNP-indicated association to a single common haplotype. By performing haplotype analyses in each population separately, as well as in a combined group of the four populations that reach the significant threshold after correction (P < 0.008), we narrowed down the CeD-associated region from 70 to 2.8 kb (P = 1.35 × 10−44). By intersecting regulatory data from the ENCODE project, we found a functional SNP, rs4686484 (P = 3.12 × 10−49), that maps to several B-cell enhancer elements and a highly conserved region. This SNP was also predicted to change the binding motif of the transcription factors IRF4, IRF11, Nkx2.7 and Nkx2.9, suggesting its role in transcriptional regulation. We later found significantly low levels of LPP mRNA in CeD biopsies compared with controls, thus our results suggest that rs4686484 is the functional variant in this locus, while LPP expression is decreased in CeD. PMID:24334606

  6. Environmental regulatory update table

    SciTech Connect

    Brown, K.J.; Langston, M.E.; Tucker, C.S.; Reed, R.M.

    1987-06-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  7. Genetic Organization of the citCDEF Locus and Identification of mae and clyR Genes from Leuconostoc mesenteroides

    PubMed Central

    Bekal-Si Ali, Sadjia; Diviès, Charles; Prévost, Hervé

    1999-01-01

    In this paper, we describe two open reading frames coding for a NAD-dependent malic enzyme (mae) and a putative regulatory protein (clyR) found in the upstream region of citCDEFG of Leuconostoc mesenteroides subsp. cremoris 195. The transcriptional analysis of the citrate lyase locus revealed one polycistronic mRNA covering the mae and citCDEF genes. This transcript was detected only on RNA prepared from cells grown in the presence of citrate. Primer extension experiments suggest that clyR and the citrate lyase operon are expressed from a bidirectional A-T-rich promoter region located between mae and clyR. PMID:10400601

  8. Multidimensional profiles of health locus of control in Hispanic Americans.

    PubMed

    Champagne, Brian R; Fox, Rina S; Mills, Sarah D; Sadler, Georgia Robins; Malcarne, Vanessa L

    2016-10-01

    Latent profile analysis identified health locus of control profiles among 436 Hispanic Americans who completed the Multidimensional Health Locus of Control scales. Results revealed four profiles: Internally Oriented-Weak, -Moderate, -Strong, and Externally Oriented. The profile groups were compared on sociocultural and demographic characteristics, health beliefs and behaviors, and physical and mental health outcomes. The Internally Oriented-Strong group had less cancer fatalism, religiosity, and equity health attributions, and more alcohol consumption than the other three groups; the Externally Oriented group had stronger equity health attributions and less alcohol consumption. Deriving multidimensional health locus of control profiles through latent profile analysis allows examination of the relationships of health locus of control subtypes to health variables.

  9. A highly polymorphic STR locus in Cannabis sativa.

    PubMed

    Hsieh, Hsing-Mei; Hou, Rur-Jyun; Tsai, Li-Chin; Wei, Chih-Sheng; Liu, Su-Wen; Huang, Li-Hung; Kuo, Yi-Chen; Linacre, Adrian; Lee, James Chun-I

    2003-01-01

    We report on the first short tandem repeat (STR) locus to be isolated from the plant Cannabis sativa. The STR locus, isolated by a hybrid-capture enrichment procedure, was found to contain a simple sequence repeat motif of 6 bp. This 6 bp repeat motif showed no variation in repeat length but with minor variations in repeat unit sequences. The data show the locus to be highly polymorphic with the number of repeat units ranging from 3 to 40 in 108 screened samples. The observed heterozygosity was approximately 87.04%. The forward and reverse primers (CS1F and CS1R) produced no PCR products in cross-reaction study from 20 species of plants, including highly related species such as Humulus japonicus and Nicotiana tabacum. This hexanucleotide repeat DNA locus could be used to identify cannabis samples and predict their genetic relationship as the test is specific to C. sativa and is highly reproducible.

  10. The agr locus regulates virulence and colonization genes in Clostridium difficile 027.

    PubMed

    Martin, Melissa J; Clare, Simon; Goulding, David; Faulds-Pain, Alexandra; Barquist, Lars; Browne, Hilary P; Pettit, Laura; Dougan, Gordon; Lawley, Trevor D; Wren, Brendan W

    2013-08-01

    The transcriptional regulator AgrA, a member of the LytTR family of proteins, plays a key role in controlling gene expression in some Gram-positive pathogens, including Staphylococcus aureus and Enterococcus faecalis. AgrA is encoded by the agrACDB global regulatory locus, and orthologues are found within the genome of most Clostridium difficile isolates, including the epidemic lineage 027/BI/NAP1. Comparative RNA sequencing of the wild type and otherwise isogenic agrA null mutant derivatives of C. difficile R20291 revealed a network of approximately 75 differentially regulated transcripts at late exponential growth phase, including many genes associated with flagellar assembly and function, such as the major structural subunit, FliC. Other differentially regulated genes include several involved in bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) synthesis and toxin A expression. C. difficile 027 R20291 agrA mutant derivatives were poorly flagellated and exhibited reduced levels of colonization and relapses in the murine infection model. Thus, the agr locus likely plays a contributory role in the fitness and virulence potential of C. difficile strains in the 027/BI/NAP1 lineage. PMID:23772065

  11. Dynamic estrogen receptor interactomes control estrogen-responsive trefoil Factor (TFF) locus cell-specific activities.

    PubMed

    Quintin, Justine; Le Péron, Christine; Palierne, Gaëlle; Bizot, Maud; Cunha, Stéphanie; Sérandour, Aurélien A; Avner, Stéphane; Henry, Catherine; Percevault, Frédéric; Belaud-Rotureau, Marc-Antoine; Huet, Sébastien; Watrin, Erwan; Eeckhoute, Jérôme; Legagneux, Vincent; Salbert, Gilles; Métivier, Raphaël

    2014-07-01

    Estradiol signaling is ideally suited for analyzing the molecular and functional linkages between the different layers of information directing transcriptional regulations: the DNA sequence, chromatin modifications, and the spatial organization of the genome. Hence, the estrogen receptor (ER) can bind at a distance from its target genes and engages timely and spatially coordinated processes to regulate their expression. In the context of the coordinated regulation of colinear genes, identifying which ER binding sites (ERBSs) regulate a given gene still remains a challenge. Here, we investigated the coordination of such regulatory events at a 2-Mb genomic locus containing the estrogen-sensitive trefoil factor (TFF) cluster of genes in breast cancer cells. We demonstrate that this locus exhibits a hormone- and cohesin-dependent reduction in the plasticity of its three-dimensional organization that allows multiple ERBSs to be dynamically brought to the vicinity of estrogen-sensitive genes. Additionally, by using triplex-forming oligonucleotides, we could precisely document the functional links between ER engagement at given ERBSs and the regulation of particular genes. Hence, our data provide evidence of a formerly suggested cooperation of enhancers toward gene regulation and also show that redundancy between ERBSs can occur.

  12. A genetic locus essential for formate-dependent growth of Bradyrhizobium japonicum.

    PubMed Central

    McClung, C R; Chelm, B K

    1987-01-01

    A genetic locus essential for the formate-dependent growth of Bradyrhizobium japonicum was isolated by complementation of ethyl methanesulfonate-induced mutants with a cosmid gene library of B. japonicum DNA. Three related cosmids containing 18.7 kilobase pairs of B. japonicum DNA in common were identified as being able to restore formate-dependent growth capability to mutants lacking either ribulosebisphosphate carboxylase or both ribulosebisphosphate carboxylase and phosphoribulokinase activities. To further localize the complementing gene(s), a series of four deletions spanning a total of 16.1 kilobase pairs were introduced into the B. japonicum chromosome. Each resulting deletion mutant lacked formate dehydrogenase activity and lacked ribulosebisphosphate carboxylase activity and immunologically detectable protein. Three of the four also lacked phosphoribulokinase activity. Two other mutants in which the deletion-bearing recombinant plasmid had integrated into the chromosome also lacked ribulosebisphosphate carboxylase activity and protein and phosphoribulokinase activities. The genetic locus defined by these mutants could contain the structural genes for these enzymes or a regulatory gene(s) controlling their expression or both. Images PMID:3036781

  13. Dynamic Estrogen Receptor Interactomes Control Estrogen-Responsive Trefoil Factor (TFF) Locus Cell-Specific Activities

    PubMed Central

    Quintin, Justine; Le Péron, Christine; Palierne, Gaëlle; Bizot, Maud; Cunha, Stéphanie; Sérandour, Aurélien A.; Avner, Stéphane; Henry, Catherine; Percevault, Frédéric; Belaud-Rotureau, Marc-Antoine; Huet, Sébastien; Watrin, Erwan; Eeckhoute, Jérôme; Legagneux, Vincent; Salbert, Gilles

    2014-01-01

    Estradiol signaling is ideally suited for analyzing the molecular and functional linkages between the different layers of information directing transcriptional regulations: the DNA sequence, chromatin modifications, and the spatial organization of the genome. Hence, the estrogen receptor (ER) can bind at a distance from its target genes and engages timely and spatially coordinated processes to regulate their expression. In the context of the coordinated regulation of colinear genes, identifying which ER binding sites (ERBSs) regulate a given gene still remains a challenge. Here, we investigated the coordination of such regulatory events at a 2-Mb genomic locus containing the estrogen-sensitive trefoil factor (TFF) cluster of genes in breast cancer cells. We demonstrate that this locus exhibits a hormone- and cohesin-dependent reduction in the plasticity of its three-dimensional organization that allows multiple ERBSs to be dynamically brought to the vicinity of estrogen-sensitive genes. Additionally, by using triplex-forming oligonucleotides, we could precisely document the functional links between ER engagement at given ERBSs and the regulation of particular genes. Hence, our data provide evidence of a formerly suggested cooperation of enhancers toward gene regulation and also show that redundancy between ERBSs can occur. PMID:24752895

  14. Differential expression of polycytosine-binding protein isoforms in adrenal gland, locus coeruleus and midbrain.

    PubMed

    Boschi, N M; Takeuchi, K; Sterling, C; Tank, A W

    2015-02-12

    Polycytosine-binding proteins (PCBPs) are RNA-binding proteins that participate in post-transcriptional control pathways. Among the diverse functions of these proteins is the interaction with a 27 nucleotide pyrimidine-rich domain within the 3'UTR of tyrosine hydroxylase (TH) mRNA. Mutations to this domain result in decreased stability of TH mRNA and loss of cAMP-mediated activation of TH mRNA translation. PCBPs are hypothesized to play key roles in these regulatory mechanisms. In order to further test this hypothesis, we examined the tissue distribution of PCBPs in catecholaminergic cells. Initial studies demonstrated that proteins from catecholaminergic tissues bind to TH mRNA 3'UTR sequences and these proteins have an apparent Mr of ∼ 44 kDa, which is close to the molecular sizes for PCBPs. Fluorescent immunohistochemistry and confocal microscopy was used to analyze the distribution of PCBP isoforms in TH-positive cells of the rat midbrain, locus coeruleus, and adrenal gland. Our results suggest that: (1) PCBP2 is the predominant isoform in TH-positive cells of the rat midbrain; (2) PCBP3 is the predominant isoform in TH-positive cells of the locus coeruleus; and (3) PCBP1 is the predominant isoform in the adrenal medulla. The localization of PCBP proteins to TH-positive cells in these catecholaminergic tissues is consistent with the hypothesis that PCBPs play a role in the regulation of TH expression.

  15. Type III secretion genes identify a putative virulence locus of Chlamydia.

    PubMed

    Hsia, R C; Pannekoek, Y; Ingerowski, E; Bavoil, P M

    1997-07-01

    Four genes of Chlamydia psittaci strain guinea pig inclusion conjunctivitis (GPIC), whose predicted products are highly homologous to structural and regulatory components of a contact-dependent or type III secretion apparatus, were isolated. Related to genes present in several animal and plant bacterial pathogens, these genes may represent a section of a previously undetected chromosomal virulence locus analogous to several recently described virulence-associated type III secretion loci. The existence of contact-dependent secretion in Chlamydia strongly suggests that these bacteria use pathogenic mechanisms that are similar to those of other intracellular bacterial pathogens. Unlike other intracellular bacteria, however, chlamydiae are metabolically inactive extracellularly and only become capable of global protein synthesis several hours after infection. This implies that chlamydial contact-dependent secretion is only active from within, uniquely after the bacteria have been internalized by eukaryotic cells. The possible role(s) of this pathway in chlamydial pathogenesis are discussed.

  16. Two-locus linkage analysis in multiple sclerosis (MS)

    SciTech Connect

    Tienari, P.J. Univ. of Helsinki ); Terwilliger, J.D.; Ott, J. ); Palo, J. ); Peltonen, L. )

    1994-01-15

    One of the major challenges in genetic linkage analyses is the study of complex diseases. The authors demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, they have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family member than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested. 41 refs., 6 tabs.

  17. Neurolinguistic programming training, trait anxiety, and locus of control.

    PubMed

    Konefal, J; Duncan, R C; Reese, M A

    1992-06-01

    Training in the neurolinguistic programming techniques of shifting perceptual position, visual-kinesthetic dissociation, timelines, and change-history, all based on experiential cognitive processing of remembered events, leads to an increased awareness of behavioral contingencies and a more sensitive recognition of environmental cues which could serve to lower trait anxiety and increase the sense of internal control. This study reports on within-person and between-group changes in trait anxiety and locus of control as measured on the Spielberger State-Trait Anxiety Inventory and Wallston, Wallston, and DeVallis' Multiple Health Locus of Control immediately following a 21-day residential training in neurolinguistic programming. Significant with-in-person decreases in trait-anxiety scores and increases in internal locus of control scores were observed as predicted. Chance and powerful other locus of control scores were unchanged. Significant differences were noted on trait anxiety and locus of control scores between European and U.S. participants, although change scores were similar for the two groups. These findings are consistent with the hypothesis that this training may lower trait-anxiety scores and increase internal locus of control scores. A matched control group was not available, and follow-up was unfortunately not possible. PMID:1620774

  18. [Health locus of control of patients in disease management programmes].

    PubMed

    Schnee, M; Grikscheit, F

    2013-06-01

    Health locus of control beliefs plays a major role in improving self-management skills of the chronically ill - a main goal in disease management programmes (DMP). This study aims at characterising participants in disease management regarding their health locus of control. Data are based on 4 cross-sectional postal surveys between spring and autumn of 2006 and 2007 within the Health Care Monitor of the Bertelsmann Foundation. Among the 6 285 respondents, 1 266 are chronically ill and not enrolled in a DMP and 327 are participating in a DMP. A high internal locus of control (HLC) occurs significantly less often in DMP patients than in normal chronically ill patients (and healthy people) controlling for age, gender and social class. With increasing age, a high internal locus of control is also significantly less likely. When comparing healthy people, the chronically ill and the DMP participants a social gradient of a high internal locus of control belief can be observed. The weaker internal and higher doctor-related external locus of control of DMP participants should be carefully observed by the physician when trying to strengthen the patients' self-management skills. Evaluators of DMP should take into account the different baselines of DMP patients and relevant control groups and incorporate these differences into the evaluation.

  19. DNA Modification Study of Major Depressive Disorder: Beyond Locus-by-Locus Comparisons

    PubMed Central

    Oh, Gabriel; Wang, Sun-Chong; Pal, Mrinal; Chen, Zheng Fei; Khare, Tarang; Tochigi, Mamoru; Ng, Catherine; Yang, Yeqing A.; Kwan, Andrew; Kaminsky, Zachary A.; Mill, Jonathan; Gunasinghe, Cerisse; Tackett, Jennifer L.; Gottesman, Irving I.; Willemsen, Gonneke; de Geus, Eco J.C.; Vink, Jacqueline M.; Slagboom, P. Eline; Wray, Naomi R.; Heath, Andrew C.; Montgomery, Grant W.; Turecki, Gustavo; Martin, Nicholas G.; Boomsma, Dorret I.; McGuffin, Peter; Kustra, Rafal; Petronis, Art

    2014-01-01

    Background Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. Methods We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. Results In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. Conclusions Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations. PMID:25108803

  20. The human growth hormone gene is regulated by a multicomponent locus control region.

    PubMed Central

    Jones, B K; Monks, B R; Liebhaber, S A; Cooke, N E

    1995-01-01

    The five-member human growth hormone (hGH)/chorionic somatomammotropin (hCS) gene cluster encodes the pituitary-specific hGH-N gene and four highly related genes (hGH-V, hCS-A, hCS-B, and hCS-L) that are expressed only in the placenta. When the hGH-N or hCS-A gene, together with all previously identified cis-acting regulatory sequences, was integrated into the mouse genome, it was expressed only sporadically and at low levels in the transgenic target organs. DNase I mapping of chromatin from expressing and nonexpressing cell types was used to identify a pituitary-specific set of DNase I-hypersensitive sites (HS) and a set of HS common to both the pituitary and placenta, centered approximately 15 and 30 kb 5' of hGH-N, respectively. When contained on a cosmid insert in their native genomic configuration, these HS consistently directed high-level, pituitary-specific expression of hGH-N in transgenic mice and appeared to define a locus control region required for hGH-N expression. Individually, each set of HS was able to mediate position-independent hGH-N expression in the pituitary but demonstrated loss of physiologic control and loss of tissue specificity. The gene-proximal set of HS contained a potent enhancer activity in the pituitary, while the more distal set appeared to function primarily to establish site-of-integration independence. These data indicate that synergistic interactions among multiple elements are required to restrict hGH-N transcription to the pituitary and generate appropriate levels of expression. In addition, these results suggest a role for both shared and unique regulatory sequences in locus control region-mediated expression of the hGH/hCS gene cluster in the pituitary and possibly the placenta. PMID:8524268

  1. Flowering time modulation by a vacuolar SNARE via FLOWERING LOCUS C in Arabidopsis thaliana.

    PubMed

    Ebine, Kazuo; Uemura, Tomohiro; Nakano, Akihiko; Ueda, Takashi

    2012-01-01

    The transition of plant growth from vegetative to reproductive phases is one of the most important and dramatic events during the plant life cycle. In Arabidopsis thaliana, flowering promotion involves at least four genetically defined regulatory pathways, including the photoperiod-dependent, vernalization-dependent, gibberellin-dependent, and autonomous promotion pathways. Among these regulatory pathways, the vernalization-dependent and autonomous pathways are integrated by the expression of FLOWERING LOCUS C (FLC), a negative regulator of flowering; however, the upstream regulation of this locus has not been fully understood. The SYP22 gene encodes a vacuolar SNARE protein that acts in vacuolar and endocytic trafficking pathways. Loss of SYP22 function was reported to lead to late flowering in A. thaliana plants, but the mechanism has remained completely unknown. In this study, we demonstrated that the late flowering phenotype of syp22 was due to elevated expression of FLC caused by impairment of the autonomous pathway. In addition, we investigated the DOC1/BIG pathway, which is also suggested to regulate vacuolar/endosomal trafficking. We found that elevated levels of FLC transcripts accumulated in the doc1-1 mutant, and that syp22 phenotypes were exaggerated with a double syp22 doc1-1 mutation. We further demonstrated that the elevated expression of FLC was suppressed by ara6-1, a mutation in the gene encoding plant-unique Rab GTPase involved in endosomal trafficking. Our results indicated that vacuolar and/or endocytic trafficking is involved in the FLC regulation of flowering time in A. thaliana.

  2. Nuclear Regulatory Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... agenda on April 26, 2010 (75 FR 21960). For this edition of the NRC's regulatory agenda, the most... publication of the last NRC semiannual agenda on April 26, 2010 (75 FR 21960). Within each group, the rules... regulations to improve the control over the distribution of source material to exempt persons and to...

  3. Copy Number Variation and Transposable Elements Feature in Recent, Ongoing Adaptation at the Cyp6g1 Locus

    PubMed Central

    Schmidt, Joshua M.; Good, Robert T.; Appleton, Belinda; Sherrard, Jayne; Raymant, Greta C.; Bogwitz, Michael R.; Martin, Jon; Daborn, Phillip J.; Goddard, Mike E.; Batterham, Philip; Robin, Charles

    2010-01-01

    The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation mediated by cis-regulatory change. A fragment of an Accord transposable element inserted upstream of the Cyp6g1 gene is causally associated with resistance and has spread to high frequencies in populations around the world since the 1940s. Here we report the existence of a natural allelic series at this locus of D. melanogaster, involving copy number variation of Cyp6g1, and two additional transposable element insertions (a P and an HMS-Beagle). We provide evidence that this genetic variation underpins phenotypic variation, as the more derived the allele, the greater the level of DDT resistance. Tracking the spatial and temporal patterns of allele frequency changes indicates that the multiple steps of the allelic series are adaptive. Further, a DDT association study shows that the most resistant allele, Cyp6g1-[BP], is greatly enriched in the top 5% of the phenotypic distribution and accounts for ∼16% of the underlying phenotypic variation in resistance to DDT. In contrast, copy number variation for another candidate resistance gene, Cyp12d1, is not associated with resistance. Thus the Cyp6g1 locus is a major contributor to DDT resistance in field populations, and evolution at this locus features multiple adaptive steps occurring in rapid succession. PMID:20585622

  4. Epigenetic Properties and Identification of an Imprint Mark in the Nesp-Gnasxl Domain of the Mouse Gnas Imprinted Locus

    PubMed Central

    Coombes, Candice; Arnaud, Philippe; Gordon, Emma; Dean, Wendy; Coar, Elizabeth A.; Williamson, Christine M.; Feil, Robert; Peters, Jo; Kelsey, Gavin

    2003-01-01

    The Gnas locus in the mouse is imprinted with a complex arrangement of alternative transcripts defined by promoters with different patterns of monoallelic expression. The Gnas transcript is subject to tissue-specific imprinted expression, Nesp is expressed only from the maternal allele, and Gnasxl is expressed only from the paternal allele. The mechanisms controlling these expression patterns are not known. To identify potential imprinting regulatory regions, particularly for the reciprocally expressed Nesp and Gnasxl promoters, we examined epigenetic properties of the locus in gametes, embryonic stem cells, and fetal and adult tissues. The Nesp and Gnasxl promoter regions are contained in extensive CpG islands with methylation of the paternal allele at Nesp and the maternal allele at Gnasxl. Parental allele-specific DNase I-hypersensitive sites were found at these regions, which correlate with hypomethylation rather than actual expression status. A germ line methylation mark was identified covering the promoters for Gnasxl and the antisense transcript Nespas. Prominent DNase I-hypersensitive sites present on paternal alleles in embryonic stem cells are contained within this mark. This is the second gametic mark identified at Gnas and suggests that the Nesp and Gnasxl promoters are under separate control from the Gnas promoter. We propose models to account for the regulation of imprinting at the locus. PMID:12897124

  5. Murine lupus susceptibility locus Sle1a requires the expression of two sub-loci to induce inflammatory T cells.

    PubMed

    Cuda, C M; Zeumer, L; Sobel, E S; Croker, B P; Morel, L

    2010-10-01

    The NZM2410-derived Sle1a lupus susceptibility locus induces activated autoreactive CD4(+) T cells and reduces the number and function of Foxp3(+) regulatory T cells (Tregs). In this study, we first showed that Sle1a contributes to autoimmunity by increasing antinuclear antibody production when expressed on either NZB or NZW heterozygous genomes, and by enhancing the chronic graft versus host disease response indicating an expansion of the autoreactive B-cell pool. Screening two non-overlapping recombinants, the Sle1a.1 and Sle1a.2 intervals that cover the entire Sle1a locus, revealed that both Sle1a.1 and Sle1a.2 were necessary for the full Sle1a phenotype. Sle1a.1, and to a lesser extent Sle1a.2, significantly affected CD4(+) T-cell activation as well as Treg differentiation and function. Sle1a.2 also increased the production of autoreactive B cells. As the Sle1a.1 and Sle1a.2 intervals contain only 1 and 15 known genes, respectively, this study considerably reduces the number of candidate genes responsible for the production of autoreactive T cells. These results also show that the Sle1 locus is an excellent model for the genetic architecture of lupus, in which a major obligate phenotype results from the coexpression of multiple genetic variants with individual weak effects.

  6. Characterization of the bvgR Locus of Bordetella pertussis

    PubMed Central

    Merkel, Tod J.; Barros, Cassia; Stibitz, Scott

    1998-01-01

    Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors is dependent upon the bvg locus (originally designated the vir locus), which encodes two proteins: BvgA, a 23-kDa cytoplasmic protein, and BvgS, a 135-kDa transmembrane protein. It is proposed that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regulator which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the bvg locus. Expression of this class, the bvg-repressed genes (vrgs [for vir-repressed genes]), is reduced under conditions in which expression of the aforementioned bvg-activated virulence factors is maximal; this repression is dependent upon the presence of an intact bvgAS locus. We have previously identified a locus required for regulation of all of the known bvg-repressed genes in B. pertussis. This locus, designated bvgR, maps to a location immediately downstream of bvgAS. We have undertaken deletion and complementation studies, as well as sequence analysis, in order to identify the bvgR open reading frame and identify the cis-acting sequences required for regulated expression of bvgR. Studies utilizing transcriptional fusions of bvgR to the gene encoding alkaline phosphatase have demonstrated that bvgR is activated at the level of transcription and that this activation is dependent upon an intact bvgAS locus. PMID:9537363

  7. Regulatory guidance document

    SciTech Connect

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

  8. lcrR, a low-Ca2(+)-response locus with dual Ca2(+)-dependent functions in Yersinia pestis.

    PubMed Central

    Barve, S S; Straley, S C

    1990-01-01

    The low-Ca2+ response (Lcr) of Yersinia includes a regulatory cascade and a set of virulence-related proteins, one of which is the V antigen. The regulatory genes modulate both bacterial growth and expression of the virulence-related proteins in response to temperature and the presence of Ca2+ and nucleotides. In this study we defined a new Lcr locus, lcrR, in Yersinia pestis KIM. An lcrR mutant, obtained by insertion mutagenesis, failed to grow at 37 degrees C whether Ca2+ was present or not. However, it grew normally in the presence of ATP, showing that the Ca2(+)- and nucleotide-responsive mechanisms are separate in Y. pestis. The lcrR mutant was avirulent in mice, probably due to its compromised growth at 37 degrees C. beta-Galactosidase measurements and Northern (RNA blot) analysis revealed that lcrR transcription was regulated primarily by temperature. The DNA sequence of the lcrR locus contained a single open reading frame of 441 bases that could encode a protein with a molecular weight of 16,470 and a pI of 10.73. Expression of an lcrR-containing clone in Escherichia coli yielded a 16,000-molecular-weight protein. At 37 degrees C, the lcrR mutant strongly expressed V antigen and initiated lcrGVH transcription whether Ca2+ was present or not, indicating that this mutant had lost the transcriptional downregulation of lcrGVH shown by the parent in the presence of Ca2+. In the absence of Ca2+, the mutant failed to express LcrG, even though lcrGVH mRNA initiated upstream of lcrG at the normal sites. These data suggest that the lcrR locus is necessary for the regulation of LcrG expression in the absence of Ca2+. Therefore, this locus has a dual regulatory role in the low-Ca2+ response. Images PMID:1695896

  9. Application of ADA1 as a new marker enzyme in sandwich ELISA to study the effect of adenosine on activated monocytes

    PubMed Central

    Liu, Chengqian; Skaldin, Maksym; Wu, Chengxiang; Lu, Yuanan; Zavialov, Andrey V.

    2016-01-01

    Enzyme-linked immunosorbent assay (ELISA) is a valuable technique to detect antigens in biological fluids. Horse radish peroxidase (HRP) is one of the most common enzymes used for signal amplification in ELISA. Despite new advances in technology, such as a large-scale production of recombinant enzymes and availability of new detection systems, limited research is devoted to finding alternative enzymes and their substrates to amplify the ELISA signals. Here, HRP-avidin was substituted with the human adenosine deaminase (hADA1)-streptavidin complex and adenosine as a detection system in commercial ELISA kits. The hADA1 ELISA was successfully used to demonstrate that adenosine, bound to A1 and A3 adenosine receptors, increases cytokine secretion by LPS activated monocytes. We show that hADA1-based ELISA has the same sensitivity, and also provides identical results, as HRP ELISA. In addition, the sensitivity of hADA1-based ELISA could be easily adjusted by changing the adenosine concentration and the incubation time. Therefore, hADA1 could be used as a detection enzyme with any commercial ELISA kit with a wide range of concentration of antigens. PMID:27510152

  10. An AdaBoost Using a Weak-Learner Generating Several Weak-Hypotheses for Large Training Data of Natural Language Processing

    NASA Astrophysics Data System (ADS)

    Iwakura, Tomoya; Okamoto, Seishi; Asakawa, Kazuo

    AdaBoost is a method to create a final hypothesis by repeatedly generating a weak hypothesis in each training iteration with a given weak learner. AdaBoost-based algorithms are successfully applied to several tasks such as Natural Language Processing (NLP), OCR, and so on. However, learning on the training data consisting of large number of samples and features requires long training time. We propose a fast AdaBoost-based algorithm for learning rules represented by combination of features. Our algorithm constructs a final hypothesis by learning several weak-hypotheses at each iteration. We assign a confidence-rated value to each weak-hypothesis while ensuring a reduction in the theoretical upper bound of the training error of AdaBoost. We evaluate our methods with English POS tagging and text chunking. The experimental results show that the training speed of our algorithm are about 25 times faster than an AdaBoost-based learner, and about 50 times faster than Support Vector Machines with polynomial kernel on the average while maintaining state-of-the-art accuracy.

  11. Application of ADA1 as a new marker enzyme in sandwich ELISA to study the effect of adenosine on activated monocytes.

    PubMed

    Liu, Chengqian; Skaldin, Maksym; Wu, Chengxiang; Lu, Yuanan; Zavialov, Andrey V

    2016-01-01

    Enzyme-linked immunosorbent assay (ELISA) is a valuable technique to detect antigens in biological fluids. Horse radish peroxidase (HRP) is one of the most common enzymes used for signal amplification in ELISA. Despite new advances in technology, such as a large-scale production of recombinant enzymes and availability of new detection systems, limited research is devoted to finding alternative enzymes and their substrates to amplify the ELISA signals. Here, HRP-avidin was substituted with the human adenosine deaminase (hADA1)-streptavidin complex and adenosine as a detection system in commercial ELISA kits. The hADA1 ELISA was successfully used to demonstrate that adenosine, bound to A1 and A3 adenosine receptors, increases cytokine secretion by LPS activated monocytes. We show that hADA1-based ELISA has the same sensitivity, and also provides identical results, as HRP ELISA. In addition, the sensitivity of hADA1-based ELISA could be easily adjusted by changing the adenosine concentration and the incubation time. Therefore, hADA1 could be used as a detection enzyme with any commercial ELISA kit with a wide range of concentration of antigens. PMID:27510152

  12. Synthesis of an A-D-A type of molecule used as electron acceptor for improving charge transfer in organic solar cells

    NASA Astrophysics Data System (ADS)

    Zhang, Chao-Zhi; Gu, Shu-Duo; Shen, Dan; Yuan, Yang; Zhang, Mingdao

    2016-08-01

    Electron-accepting molecules play an important role in developing organic solar cells. A new type of A-D-A molecule, 3,6-di([7-(5-bromothiophen-2-yl)-1,5,2,4,6,8-dithiotetrazocin-3-yl]thiophen-2-yl)-9-(2-ethylhexyl)carbazole, was synthesized. The lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels are -3.55 and -5.85 eV, respectively. Therefore, the A-D-A type of compound could be used as electron acceptor for fabricating organic solar cell with a high open circuit voltage. Gibbs free energy (-49.2 kJ/mol) reveals that the process of A-D-A acceptor accepting an electron from poly(3-hexylthiophene) at excited state is spontaneous. The value of entropy (118 J/mol) in the process of an electron transferring from P3HT to the A-D-A acceptor at organic interface suggests that electrons generated from separation of electron-hole pairs at donor/acceptor interface would be delocalized efficiently. Therefore, the A-D-A molecule would be a potential acceptor for efficient organic BHJ solar cells.

  13. Locus equations are an acoustic expression of articulator synergy

    PubMed Central

    Iskarous, Khalil; Fowler, Carol A.; Whalen, D. H.

    2010-01-01

    The study investigated the articulatory basis of locus equations, regression lines relating F2 at the start of a Consonant-Vowel (CV) transition to F2 at the middle of the vowel, with C fixed and V varying. Several studies have shown that consonants of different places of articulation have locus equation slopes that descend from labial to velar to alveolar, and intercept magnitudes that increase in the opposite order. Using formulas from the theory of bivariate regression that express regression slopes and intercepts in terms of standard deviations and averages of the variables, it is shown that the slope directly encodes a well-established measure of coarticulation resistance. It is also shown that intercepts are directly related to the degree to which the tongue body assists the formation of the constriction for the consonant. Moreover, it is shown that the linearity of locus equations and the linear relation between locus equation slopes and intercepts originates in linearity in articulation between the horizontal position of the tongue dorsum in the consonant and to that in the vowel. It is concluded that slopes and intercepts of acoustic locus equations are measures of articulator synergy. PMID:20968373

  14. Regulatory sequence analysis tools.

    PubMed

    van Helden, Jacques

    2003-07-01

    The web resource Regulatory Sequence Analysis Tools (RSAT) (http://rsat.ulb.ac.be/rsat) offers a collection of software tools dedicated to the prediction of regulatory sites in non-coding DNA sequences. These tools include sequence retrieval, pattern discovery, pattern matching, genome-scale pattern matching, feature-map drawing, random sequence generation and other utilities. Alternative formats are supported for the representation of regulatory motifs (strings or position-specific scoring matrices) and several algorithms are proposed for pattern discovery. RSAT currently holds >100 fully sequenced genomes and these data are regularly updated from GenBank.

  15. Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes.

    PubMed

    Small, Kerrin S; Hedman, Asa K; Grundberg, Elin; Nica, Alexandra C; Thorleifsson, Gudmar; Kong, Augustine; Thorsteindottir, Unnur; Shin, So-Youn; Richards, Hannah B; Soranzo, Nicole; Ahmadi, Kourosh R; Lindgren, Cecilia M; Stefansson, Kari; Dermitzakis, Emmanouil T; Deloukas, Panos; Spector, Timothy D; McCarthy, Mark I

    2011-06-01

    Genome-wide association studies have identified many genetic variants associated with complex traits. However, at only a minority of loci have the molecular mechanisms mediating these associations been characterized. In parallel, whereas cis regulatory patterns of gene expression have been extensively explored, the identification of trans regulatory effects in humans has attracted less attention. Here we show that the type 2 diabetes and high-density lipoprotein cholesterol-associated cis-acting expression quantitative trait locus (eQTL) of the maternally expressed transcription factor KLF14 acts as a master trans regulator of adipose gene expression. Expression levels of genes regulated by this trans-eQTL are highly correlated with concurrently measured metabolic traits, and a subset of the trans-regulated genes harbor variants directly associated with metabolic phenotypes. This trans-eQTL network provides a mechanistic understanding of the effect of the KLF14 locus on metabolic disease risk and offers a potential model for other complex traits. PMID:21572415

  16. Rapid, large-scale purification and characterization of 'Ada protein' (O6 methylguanine-DNA methyltransferase) of E. coli.

    PubMed Central

    Bhattacharyya, D; Tano, K; Bunick, G J; Uberbacher, E C; Behnke, W D; Mitra, S

    1988-01-01

    The E. coli Ada protein (O6-methylguanine-DNA methyltransferase) has been purified using a high-level expression vector with a yield of about 3 mg per liter of E. coli culture. The 39-kDa protein has an extinction coefficient (E280 nm (1%)) of 5.3. Its isoelectric point of 7.1 is lower than that predicted from the amino acid content. The homogeneous Ada protein is fully active as a methyl acceptor from O6-methylguanine in DNA. Its reaction with O6-methylguanine in a synthetic DNA has a second-order rate constant of 1.1 x 10(9) M-1 min-1 at O degree C. Both the native form and the protein methylated at Cys-69 are monomeric. The CD spectrum suggests a low alpha-helical content and the radius of gyration of 23 A indicates a compact, globular shape. The middle region of the protein is sensitive to a variety of proteases, including an endogenous activity in E. coli, suggesting that the protein is composed of N-terminal and C-terminal domains connected by a hinge region. E. coli B has a higher level of this protease than does K12. Images PMID:3041376

  17. AdaRTE: adaptable dialogue architecture and runtime engine. A new architecture for health-care dialogue systems.

    PubMed

    Rojas-Barahona, L M; Giorgino, T

    2007-01-01

    Spoken dialogue systems have been increasingly employed to provide ubiquitous automated access via telephone to information and services for the non-Internet-connected public. In the health care context, dialogue systems have been successfully applied. Nevertheless, speech-based technology is not easy to implement because it requires a considerable development investment. The advent of VoiceXML for voice applications contributed to reduce the proliferation of incompatible dialogue interpreters, but introduced new complexity. As a response to these issues, we designed an architecture for dialogue representation and interpretation, AdaRTE, which allows developers to layout dialogue interactions through a high level formalism that offers both declarative and procedural features. AdaRTE aim is to provide a ground for deploying complex and adaptable dialogues whilst allows the experimentation and incremental adoption of innovative speech technologies. It provides the dynamic behavior of Augmented Transition Networks and enables the generation of different backends formats such as VoiceXML. It is especially targeted to the health care context, where a framework for easy dialogue deployment could reduce the barrier for a more widespread adoption of dialogue systems. PMID:17911878

  18. Region based stellate features combined with variable selection using AdaBoost learning in mammographic computer-aided detection.

    PubMed

    Kim, Dae Hoe; Choi, Jae Young; Ro, Yong Man

    2015-08-01

    In this paper, a new method is developed for extracting so-called region-based stellate features to correctly differentiate spiculated malignant masses from normal tissues on mammograms. In the proposed method, a given region of interest (ROI) for feature extraction is divided into three individual subregions, namely core, inner, and outer parts. The proposed region-based stellate features are then extracted to encode the different and complementary stellate pattern information by computing the statistical characteristics for each of the three different subregions. To further maximize classification performance, a novel variable selection algorithm based on AdaBoost learning is incorporated for choosing an optimal subset of variables of region-based stellate features. In particular, we develop a new variable selection metric (criteria) that effectively determines variable importance (ranking) within the conventional AdaBoost framework. Extensive and comparative experiments have been performed on the popular benchmark mammogram database (DB). Results show that our region-based stellate features (extracted from automatically segmented ROIs) considerably outperform other state-of-the-art features developed for mammographic spiculated mass detection or classification. Our results also indicate that combining region-based stellate features with the proposed variable selection strategy has an impressive effect on improving spiculated mass classification and detection.

  19. Altered E-NTPDase/E-ADA activities and CD39 expression in platelets of sickle cell anemia patients.

    PubMed

    Castilhos, Lívia G; Doleski, Pedro H; Adefegha, Stephen A; Becker, Lara V; Ruchel, Jader B; Leal, Daniela B R

    2016-04-01

    Sickle cell anemia (SCA) is a hemoglobinopathy characterized by hemolysis and vaso-occlusions caused by rigidly distorted red blood cells. Sickle cell crisis is associated with extracellular release of nucleotides and platelets, which are critical mediators of hemostasis participating actively in purinergic thromboregulatory enzymes system.This study aimed to investigate the activities of purinergic system ecto-enzymes present on the platelet surface as well as CD39 and CD73 expressions on platelets of SCA treated patients. Fifteen SCA treated patients and 30 health subjects (control group) were selected. Ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-5'-nucleotidase (E-5'-NT) and ecto-adenosine deaminase (E-ADA) activities were measured in platelets isolated from these individuals. Results demonstrated an increase of 41 % in the E-NTPDase for ATP hydrolysis, 52% for ADP hydrolysis and 60 % in the E-ADA activity in SCA patients (P<0.05); however, a two folds decrease in the CD39 expression in platelets was observed in the same group (P<0.01). The increased E-NTPDase activity could be a compensatory mechanism associated with the low expression of CD39 in platelets. Besides, alteration of these enzymes activities suggests that the purinergic system could be involved in the thromboregulatory process in SCA patients. PMID:27044834

  20. Regulation of a duplicated locus: Drosophila sloppy paired is replete with functionally overlapping enhancers.

    PubMed

    Fujioka, Miki; Jaynes, James B

    2012-02-15

    In order to investigate regulation and redundancy within the sloppy paired (slp) locus, we analyzed 30 kilobases of DNA encompassing the tandem, coordinately regulated slp1 and slp2 transcription units. We found a remarkable array of stripe enhancers with overlapping activities surrounding the slp1 transcription unit, and, unexpectedly, glial cell enhancers surrounding slp2. The slp stripe regulatory region generates 7 stripes at blastoderm, and later 14 stripes that persist throughout embryogenesis. Phylogenetic analysis among drosophilids suggests that the multiplicity of stripe enhancers did not evolve through recent duplication. Most of the direct integration among cis-regulatory modules appears to be simply additive, with one notable exception. Despite the apparent redundancy among stripe enhancers, transgenic rescue suggests that most are required for full function, to maintain wingless expression and parasegment boundaries throughout embryogenesis. Transgenic rescue also reveals indirect positive autoregulation by the 7 early stripes, without which alternate stripes within the 14-stripe pattern are lost, leading to embryos with a pair-rule phenotype.

  1. Endogenous retroviral long terminal repeats within the HLA-DQ locus.

    PubMed Central

    Kambhu, S; Falldorf, P; Lee, J S

    1990-01-01

    Two endogenous retroviral long terminal repeats (LTRs) were found in the human major histocompatibility complex locus HLA-DQ. The solo LTRs, unlinked to retrovirus structural genes, are located approximately 5 kilobases apart from each other and in the same transcriptional orientation, which is opposite to that for the HLA-DQB1 gene. These elements exhibit greater than 90% homology to the LTRs of the human endogenous retrovirus HERV-K10. The conservation of putative regulatory elements found within the LTRs and their position relative to the HLA-DQB1 gene suggest that these elements may confer distinct regulatory properties on genes in the HLA-DQ region. Polymorphic variation between different HLA haplotypes for the presence of the LTRs at this location and of the molecular architecture within this subregion is supported by polymerase chain reaction and Southern blot analysis. Comparisons of chromosomes with and without the LTRs in this region will provide a unique opportunity in the human genome to analyze transposition or integration of retroviral sequences. Images PMID:2114643

  2. 3 CFR - Regulatory Review

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... been learned since that time. Far more is now known about regulation—not only about when it is... interests of future generations; identify methods of ensuring that regulatory review does not produce...

  3. Two-locus sampling distributions and their application.

    PubMed Central

    Hudson, R R

    2001-01-01

    Methods of estimating two-locus sample probabilities under a neutral model are extended in several ways. Estimation of sample probabilities is described when the ancestral or derived status of each allele is specified. In addition, probabilities for two-locus diploid samples are provided. A method for using these two-locus probabilities to test whether an observed level of linkage disequilibrium is unusually large or small is described. In addition, properties of a maximum-likelihood estimator of the recombination parameter based on independent linked pairs of sites are obtained. A composite-likelihood estimator, for more than two linked sites, is also examined and found to work as well, or better, than other available ad hoc estimators. Linkage disequilibrium in the Xq28 and Xq25 region of humans is analyzed in a sample of Europeans (CEPH). The estimated recombination parameter is about five times smaller than one would expect under an equilibrium neutral model. PMID:11779816

  4. Tension versus ecological zones in a two-locus system.

    PubMed

    Hu, Xin-Sheng

    2005-08-01

    Previous theories show that tension and ecological zones are indistinguishable in terms of gene frequency clines. Here I analytically show that these two types of zones can be distinguished in terms of genetic statistics other than gene frequency. A two-locus cline model is examined with the assumptions of random mating, weak selection, no drift, no mutation, and multiplicative viabilities. The genetic statistics for distinguishing the two types of zones are the deviations of one- or two-locus genotypic frequencies from Hardy-Weinberg equilibrium (HWE) or from random association of gametes (RAG), and the deviations of additive and dominance variances from the values at HWE. These deviations have a discontinuous distribution in space and different extents of interruptions in the ecological zone with a sharp boundary, but exhibit a continuous distribution in the tension zone. Linkage disequilibrium enhances the difference between the deviations from HWE and from RAG for any two-locus genotypic frequency.

  5. Function and evolution of local repeats in the Firre locus

    PubMed Central

    Hacisuleyman, Ezgi; Shukla, Chinmay J.; Weiner, Catherine L.; Rinn, John L.

    2016-01-01

    More than half the human and mouse genomes are comprised of repetitive sequences, such as transposable elements (TEs), which have been implicated in many biological processes. In contrast, much less is known about other repeats, such as local repeats that occur in multiple instances within a given locus in the genome but not elsewhere. Here, we systematically characterize local repeats in the genomic locus of the Firre long noncoding RNA (lncRNA). We find a conserved function for the RRD repeat as a ribonucleic nuclear retention signal that is sufficient to retain an otherwise cytoplasmic mRNA in the nucleus. We also identified a repeat, termed R0, that can function as a DNA enhancer element within the intronic sequences of Firre. Collectively, our data suggest that local repeats can have diverse functionalities and molecular modalities in the Firre locus and perhaps more globally in other lncRNAs. PMID:27009974

  6. Molecular organization of the cut locus of Drosophila melanogaster.

    PubMed

    Jack, J W

    1985-10-01

    Mutations of the cut locus (ct) of Drosophila can be divided into four groups based on their phenotypes and complementation patterns. Each group alters the phenotype of a different set of tissues. Two hundred kilobases of ct DNA, located in 7B1-2, have been cloned by chromosomal walking, and the cloned sequences have been used to analyze more than 40 mutants. Based on the location of transposable element mutations and the extent of deficiencies and an inversion, four cut locus regions can be defined. Mutations in each region affect the phenotype of a different set of tissues. The most centromere proximal region contains mutations that are null for cut locus function. Within individual regions, a higher level of organization can be detected. PMID:2996782

  7. Locus coeruleus syndrome as a complication of tectal surgery.

    PubMed

    Kronenburg, Annick; Spliet, Wim G; Broekman, Marike; Robe, Pierre

    2015-01-01

    We describe a case of a 48-year-old woman who underwent a resection of a tectal pilocytic astrocytoma complicated by a sequence of fluctuating consciousness, psychosis with complex hallucinations and lasting sleeping disturbances in which she vividly acts out her dreams. Based on the clinical and anatomical evidence of this case, we propose the term locus coeruleus syndrome to describe this association of iatrogenic symptoms. Along with those of the locus coeruleus, lesions of the dorsal raphe nucleus, ventral tegmentum, substantia nigra pars compacta, the superior colliculus and other peduncular lesions (such as peduncular hallucinosis) are involved in the regulation of sleep-wake/arousal, behaviour, sleeping disorders and rapid eye movement atonia. However, iatrogenic lesion of the locus coeruleus could explain the complications on all levels in our patient. PMID:25903199

  8. Assessing the regulatory picture

    SciTech Connect

    Not Available

    1994-02-01

    This article addresses the safety of the nation's drinking water supply and discusses compliance of the Clean Water Act. Right now, the shape of the regulatory future is uncertain. The results of the D-DBP regulatory negotiation are imminent. Congress is ready to begin debating reauthorization of the Safe Drinking Water Act, and utilities are trying to comply with the regulations while trying not to price water out of the reach of some of their customers.

  9. NRC regulatory initiatives

    SciTech Connect

    Johnson, T.C.

    1989-11-01

    The US Nuclear Regulatory Commission (NRC) is addressing several low-level waste disposal issues that will be important to waste generators and to States and Compacts developing new disposal capacity. These issues include Greater-Than-Class C (GTCC) waste, mixed waste, below regulatory concern (BRC) waste, and the low-level waste data base. This paper discusses these issues and their current status.

  10. Locus-specific view of flax domestication history.

    PubMed

    Fu, Yong-Bi; Diederichsen, Axel; Allaby, Robin G

    2012-01-01

    Crop domestication has been inferred genetically from neutral markers and increasingly from specific domestication-associated loci. However, some crops are utilized for multiple purposes that may or may not be reflected in a single domestication-associated locus. One such example is cultivated flax (Linum usitatissimum L.), the earliest oil and fiber crop, for which domestication history remains poorly understood. Oil composition of cultivated flax and pale flax (L. bienne Mill.) indicates that the sad2 locus is a candidate domestication locus associated with increased unsaturated fatty acid production in cultivated flax. A phylogenetic analysis of the sad2 locus in 43 pale and 70 cultivated flax accessions established a complex domestication history for flax that has not been observed previously. The analysis supports an early, independent domestication of a primitive flax lineage, in which the loss of seed dispersal through capsular indehiscence was not established, but increased oil content was likely occurred. A subsequent flax domestication process occurred that probably involved multiple domestications and includes lineages that contain oil, fiber, and winter varieties. In agreement with previous studies, oil rather than fiber varieties occupy basal phylogenetic positions. The data support multiple paths of flax domestication for oil-associated traits before selection of the other domestication-associated traits of seed dispersal loss and fiber production. The sad2 locus is less revealing about the origin of winter tolerance. In this case, a single domestication-associated locus is informative about the history of domesticated forms with the associated trait while partially informative on forms less associated with the trait.

  11. Neighborhood Vigilance, Health Locus of Control, and Smoking Abstinence

    PubMed Central

    Reitzel, Lorraine R.; Lahoti, Sejal; Li, Yisheng; Cao, Yumei; Wetter, David W.; Waters, Andrew J.; Vidrine, Jennifer Irvin

    2012-01-01

    Objectives To examine whether health locus of control mediated relations of self-reported neighborhood vigilance and biochemically verified, continuous short-term smoking abstinence among 200 smokers enrolled in a cohort study. Methods A nonparametric bootstrapping procedure was used to assess mediation. Results Health locus of control-chance mediated relations between neighborhood vigilance and smoking abstinence in analyses adjusted for sociodemographics and tobacco dependence (p < .05). Greater vigilance was associated with greater attributions that health was affected by chance, which was associated with a lower likelihood of smoking abstinence. Conclusions Results suggest that neighborhood perceptions influence residents’ attributions for health outcomes, which can affect smoking abstinence. PMID:23985180

  12. Reorganisation of Hoxd regulatory landscapes during the evolution of a snake-like body plan.

    PubMed

    Guerreiro, Isabel; Gitto, Sandra; Novoa, Ana; Codourey, Julien; Nguyen Huynh, Thi Hanh; Gonzalez, Federico; Milinkovitch, Michel C; Mallo, Moises; Duboule, Denis

    2016-01-01

    Within land vertebrate species, snakes display extreme variations in their body plan, characterized by the absence of limbs and an elongated morphology. Such a particular interpretation of the basic vertebrate body architecture has often been associated with changes in the function or regulation of Hox genes. Here, we use an interspecies comparative approach to investigate different regulatory aspects at the snake HoxD locus. We report that, unlike in other vertebrates, snake mesoderm-specific enhancers are mostly located within the HoxD cluster itself rather than outside. In addition, despite both the absence of limbs and an altered Hoxd gene regulation in external genitalia, the limb-associated bimodal HoxD chromatin structure is maintained at the snake locus. Finally, we show that snake and mouse orthologous enhancer sequences can display distinct expression specificities. These results show that vertebrate morphological evolution likely involved extensive reorganisation at Hox loci, yet within a generally conserved regulatory framework. PMID:27476854

  13. Transgene integration into the human AAVS1 locus enhances myosin II-dependent contractile force by reducing expression of myosin binding subunit 85.

    PubMed

    Mizutani, Takeomi; Li, Rui; Haga, Hisashi; Kawabata, Kazushige

    2015-09-18

    The adeno-associated virus site 1 (AAVS1) locus in the human genome is a strong candidate for gene therapy by insertion of an exogenous gene into the locus. The AAVS1 locus includes the coding region for myosin binding subunit 85 (MBS85). Although the function of MBS85 is not well understood, myosin II-dependent contractile force may be affected by altered expression of MBS85. The effect of altered expression of MBS85 on cellular contractile force should be examined prior to the application of gene therapy. In this study, we show that transgene integration into AAVS1 and consequent reduction of MBS85 expression changes myosin II-dependent cellular contractile force. We established a human fibroblast cell line with exogenous DNA knocked-in to AAVS1 (KI cells) using the CRISPR/Cas9 genome editing system. Western blotting analysis showed that KI cells had significantly reduced MBS85 expression. KI cells also showed greater cellular contractile force than control cells. The increased contractile force was associated with phosphorylation of the myosin II regulatory light chain (MRLC). Transfection of KI cells with an MBS85 expression plasmid restored cellular contractile force and phosphorylation of MRLC to the levels in control cells. These data suggest that transgene integration into the human AAVS1 locus induces an increase in cellular contractile force and thus should be considered as a gene therapy to effect changes in cellular contractile force.

  14. Transgenic mice containing a 248-kb yeast artificial chromosome carrying the human beta-globin locus display proper developmental control of human globin genes.

    PubMed Central

    Peterson, K R; Clegg, C H; Huxley, C; Josephson, B M; Haugen, H S; Furukawa, T; Stamatoyannopoulos, G

    1993-01-01

    Transgenic mice were generated using a purified 248-kb yeast artificial chromosome (YAC) bearing an intact 82-kb human beta-globin locus and 148 kb of flanking sequence. Seventeen of 148 F0 pups were transgenic. RNase protection analysis of RNA isolated from the blood of 13 gamma- and beta-globin-positive founders showed that only the human beta-globin gene was expressed in the adult founders. Studies of F1 and F2 fetuses demonstrated that the genes of the beta-locus YAC displayed the proper developmental switches in beta-like globin gene expression. Expression of epsilon- and gamma-globin, but not beta-globin, was observed in the yolk sac, there was only minor gamma and mostly beta expression in the 14-day liver, and only beta mRNA in the blood of the adult animals. Structural data showed that the locus was intact. These results indicate that it is now possible to dissect regulatory mechanisms within the context of an entire locus in vivo by using the ability to perform mutagenesis efficiently in yeast via homologous recombination, followed by purification of the altered YAC and its introduction into mice. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8356061

  15. Balancing selection on a regulatory region exhibiting ancient variation that predates human-neandertal divergence.

    PubMed

    Gokcumen, Omer; Zhu, Qihui; Mulder, Lubbertus C F; Iskow, Rebecca C; Austermann, Christian; Scharer, Christopher D; Raj, Towfique; Boss, Jeremy M; Sunyaev, Shamil; Price, Alkes; Stranger, Barbara; Simon, Viviana; Lee, Charles

    2013-04-01

    Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup) aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs) across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10⁻¹⁵). Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003) and positive Tajima's D (p = 0.00285) statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human-Neandertal divergence and is evolving under balancing selection, especially among European populations. PMID

  16. Heterotic Trait Locus (HTL) Mapping Identifies Intra-Locus Interactions That Underlie Reproductive Hybrid Vigor in Sorghum bicolor

    PubMed Central

    Ben-Israel, Imri; Kilian, Benjamin; Nida, Habte; Fridman, Eyal

    2012-01-01

    Identifying intra-locus interactions underlying heterotic variation among whole-genome hybrids is a key to understanding mechanisms of heterosis and exploiting it for crop and livestock improvement. In this study, we present the development and first use of the heterotic trait locus (HTL) mapping approach to associate specific intra-locus interactions with an overdominant heterotic mode of inheritance in a diallel population using Sorghum bicolor as the model. This method combines the advantages of ample genetic diversity and the possibility of studying non-additive inheritance. Furthermore, this design enables dissecting the latter to identify specific intra-locus interactions. We identified three HTLs (3.5% of loci tested) with synergistic intra-locus effects on overdominant grain yield heterosis in 2 years of field trials. These loci account for 19.0% of the heterotic variation, including a significant interaction found between two of them. Moreover, analysis of one of these loci (hDPW4.1) in a consecutive F2 population confirmed a significant 21% increase in grain yield of heterozygous vs. homozygous plants in this locus. Notably, two of the three HTLs for grain yield are in synteny with previously reported overdominant quantitative trait loci for grain yield in maize. A mechanism for the reproductive heterosis found in this study is suggested, in which grain yield increase is achieved by releasing the compensatory tradeoffs between biomass and reproductive output, and between seed number and weight. These results highlight the power of analyzing a diverse set of inbreds and their hybrids for unraveling hitherto unknown allelic interactions mediating heterosis. PMID:22761720

  17. Cia27 is a novel non-MHC arthritis severity locus on rat chromosome 10 syntenic to the rheumatoid arthritis 17q22-q25 locus.

    PubMed

    Brenner, M; Laragione, T; Yarlett, N C; Li, W; Mello, A; Gulko, P S

    2006-07-01

    Cia27 on rat chromosome 10 is a collagen-induced arthritis (CIA) severity quantitative trait locus originally identified in a study of (DA x ACI) F2. As an initial step towards the positional cloning of the Cia27 gene, a 17 cM (21 Mb) interval from the DA strain (arthritis-susceptible) containing the two-logarithm of odds support interval comprising Cia27 was introgressed into the ACI (arthritis-resistant) background through genotype-guided congenic breeding. ACI.DA(Cia27) congenics developed a significantly more severe form of arthritis (CIA), with a 5.9-fold increase in median arthritis severity index, a parameter known to correlate with synovial inflammation, and cartilage and bone erosions, compared with ACI (P< or =0.001). The arthritis severity enhancing effect could be detected from day 21 onwards. Rats heterozygous at the congenic interval developed a disease similar to ACI rats, suggesting that DA alleles operate in a recessive manner. Levels of autoantibodies anti-rat type II collagen did not correlate with arthritis severity. Synovial tissue mRNA levels of interleukin-1beta (IL-1beta) were significantly increased in ACI.DA(Cia27) congenics compared with ACI. These results demonstrate that Cia27 harbors a novel arthritis severity regulatory gene. The identification of this gene should facilitate the identification of the rheumatoid arthritis gene mapped to the human syntenic region on chromosome 17q22-q25. PMID:16691185

  18. On the Concept of Cis-regulatory Information: From Sequence Motifs to Logic Functions

    NASA Astrophysics Data System (ADS)

    Tarpine, Ryan; Istrail, Sorin

    The regulatory genome is about the “system level organization of the core genomic regulatory apparatus, and how this is the locus of causality underlying the twin phenomena of animal development and animal evolution” (E.H. Davidson. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution, Academic Press, 2006). Information processing in the regulatory genome is done through regulatory states, defined as sets of transcription factors (sequence-specific DNA binding proteins which determine gene expression) that are expressed and active at the same time. The core information processing machinery consists of modular DNA sequence elements, called cis-modules, that interact with transcription factors. The cis-modules “read” the information contained in the regulatory state of the cell through transcription factor binding, “process” it, and directly or indirectly communicate with the basal transcription apparatus to determine gene expression. This endowment of each gene with the information-receiving capacity through their cis-regulatory modules is essential for the response to every possible regulatory state to which it might be exposed during all phases of the life cycle and in all cell types. We present here a set of challenges addressed by our CYRENE research project aimed at studying the cis-regulatory code of the regulatory genome. The CYRENE Project is devoted to (1) the construction of a database, the cis-Lexicon, containing comprehensive information across species about experimentally validated cis-regulatory modules; and (2) the software development of a next-generation genome browser, the cis-Browser, specialized for the regulatory genome. The presentation is anchored on three main computational challenges: the Gene Naming Problem, the Consensus Sequence Bottleneck Problem, and the Logic Function Inference Problem.

  19. Dissecting a locus control region: facilitation of enhancer function by extended enhancer-flanking sequences.

    PubMed Central

    Aronow, B J; Ebert, C A; Valerius, M T; Potter, S S; Wiginton, D A; Witte, D P; Hutton, J J

    1995-01-01

    Using transgenic mice, we have defined novel gene regulatory elements, termed "facilitators." These elements bilaterally flank, by up to 1 kb, a 200-bp T-cell-specific enhancer domain in the human adenosine deaminase (ADA) gene. Facilitators were essential for gene copy-proportional and integration site-independent reporter expression in transgenic thymocytes, but they had no effect on the enhancer in transfected T cells. Both segments were required. Individual segments had no activity. A lack of facilitator function caused positional susceptibility and prevented DNase I-hypersensitive site formation at the enhancer. The segments were required to be at opposed ends of the enhancer, and they could not be grouped together. Reversing the orientation of a facilitator segment caused a partial loss of function, suggesting involvement of a stereospecific chromatin structure. trans-acting factor access to enhancer elements was modeled by exposing nuclei to a restriction endonuclease. The enhancer domain was accessible to the 4-cutter DpnII in a tissue- and cell-type-specific fashion. However, unlike DNase I hypersensitivity and gene expression, accessibility to the endonuclease could occur without the facilitator segments, suggesting that an accessible chromatin domain is an intermediate state in the activational pathway. These results suggest that facilitators (i) are distinct from yet positionally constrained to the enhancer, (ii) participate in a chromatin structure transition that is necessary for the DNase I hypersensitivity and the transcriptional activating function of the enhancer, and (iii) act after cell-type-specific accessibility to the enhancer sequences is established by factors that do not require the facilitators to be present. PMID:7823928

  20. Two-trait-locus linkage analysis: A powerful strategy for mapping complex genetic traits

    SciTech Connect

    Schork, N.J.; Boehnke, M. ); Terwilliger, J.D.; Ott, J. )

    1993-11-01

    Nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not exhibit simple Mendelian transmission. More complex models are required to explain the genetics of these important diseases. In this paper, the authors explore two-trait-locus, two-marker-locus linkage analysis in which two trait loci are mapped simultaneously to separate genetic markers. The authors compare the utility of this approach to standard one-trait-locus, one-marker-locus linkage analysis with and without allowance for heterogeneity. The authors also compare the utility of the two-trait-locus, two-marker-locus analysis to two-trait-locus, one-marker-locus linkage analysis. For common diseases, pedigrees are often bilineal, with disease genes entering via two or more unrelated pedigree members. Since such pedigrees often are avoided in linkage studies, the authors also investigate the relative information content of unilineal and bilineal pedigrees. For the dominant-or-recessive and threshold models that the authors consider, the authors find that two-trait-locus, two-marker-locus linkage analysis can provide substantially more linkage information, as measured by expected maximum lod score, than standard one-trait-locus, one-marker-locus methods, even allowing for heterogeneity, while, for a dominant-or-dominant generating model, one-locus models that allow for heterogeneity extract essentially as much information as the two-trait-locus methods. For these three models, the authors also find that bilineal pedigrees provide sufficient linkage information to warrant their inclusion in such studies. The authors discuss strategies for assessing the significance of the two linkages assumed in two-trait-locus, two-marker-locus models. 37 refs., 1 fig., 4 tabs.