Database resources of the National Center for Biotechnology Information.

PubMed

Sayers, Eric W; Barrett, Tanya; Benson, Dennis A; Bryant, Stephen H; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M; DiCuccio, Michael; Edgar, Ron; Federhen, Scott; Feolo, Michael; Geer, Lewis Y; Helmberg, Wolfgang; Kapustin, Yuri; Landsman, David; Lipman, David J; Madden, Thomas L; Maglott, Donna R; Miller, Vadim; Mizrachi, Ilene; Ostell, James; Pruitt, Kim D; Schuler, Gregory D; Sequeira, Edwin; Sherry, Stephen T; Shumway, Martin; Sirotkin, Karl; Souvorov, Alexandre; Starchenko, Grigory; Tatusova, Tatiana A; Wagner, Lukas; Yaschenko, Eugene; Ye, Jian

2009-01-01

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART) and the PubChem suite of small molecule databases. Augmenting many of the web applications is custom implementation of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

Mining Genotype-Phenotype Associations from Public Knowledge Sources via Semantic Web Querying.

PubMed

Kiefer, Richard C; Freimuth, Robert R; Chute, Christopher G; Pathak, Jyotishman

2013-01-01

Gene Wiki Plus (GeneWiki+) and the Online Mendelian Inheritance in Man (OMIM) are publicly available resources for sharing information about disease-gene and gene-SNP associations in humans. While immensely useful to the scientific community, both resources are manually curated, thereby making the data entry and publication process time-consuming, and to some degree, error-prone. To this end, this study investigates Semantic Web technologies to validate existing and potentially discover new genotype-phenotype associations in GWP and OMIM. In particular, we demonstrate the applicability of SPARQL queries for identifying associations not explicitly stated for commonly occurring chronic diseases in GWP and OMIM, and report our preliminary findings for coverage, completeness, and validity of the associations. Our results highlight the benefits of Semantic Web querying technology to validate existing disease-gene associations as well as identify novel associations although further evaluation and analysis is required before such information can be applied and used effectively.

Database resources of the National Center for Biotechnology Information.

PubMed

Sayers, Eric W; Barrett, Tanya; Benson, Dennis A; Bolton, Evan; Bryant, Stephen H; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M; DiCuccio, Michael; Federhen, Scott; Feolo, Michael; Fingerman, Ian M; Geer, Lewis Y; Helmberg, Wolfgang; Kapustin, Yuri; Landsman, David; Lipman, David J; Lu, Zhiyong; Madden, Thomas L; Madej, Tom; Maglott, Donna R; Marchler-Bauer, Aron; Miller, Vadim; Mizrachi, Ilene; Ostell, James; Panchenko, Anna; Phan, Lon; Pruitt, Kim D; Schuler, Gregory D; Sequeira, Edwin; Sherry, Stephen T; Shumway, Martin; Sirotkin, Karl; Slotta, Douglas; Souvorov, Alexandre; Starchenko, Grigory; Tatusova, Tatiana A; Wagner, Lukas; Wang, Yanli; Wilbur, W John; Yaschenko, Eugene; Ye, Jian

2011-01-01

In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Electronic PCR, OrfFinder, Splign, ProSplign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), IBIS, Biosystems, Peptidome, OMSSA, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

V2R mutations and nephrogenic diabetes insipidus.

PubMed

Bichet, Daniel G

2009-01-01

Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. Nephrogenic failure to concentrate urine maximally may be due to a defect in vasopressin-induced water permeability of the distal tubules and collecting ducts, to insufficient buildup of the corticopapillary interstitial osmotic gradient, or to a combination of these two factors. Thus, the broadest definition of the term NDI embraces any antidiuretic hormone-resistant urinary-concentrating defect, including medullary disease with low interstitial osmolality, renal failure, and osmotic diuresis. About 90% of patients with congenital NDI are males with X-linked recessive NDI (OMIM 304800)(1) and have mutations in the AVP receptor 2 (AVPR2) gene that codes for the vasopressin V(2) receptor; the gene is located in chromosome region Xq28. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800)(1). Mutations have been identified in the aquaporin-2 gene (AQP2, OMIM 107777)(1), which is located in chromosome region 12q13 and codes for the vasopressin-sensitive water channel. NDI is clinically distinguishable from neurohypophyseal diabetes insipidus (OMIM 125700(1); also referred to as central or neurogenic diabetes insipidus) by a lack of response to exogenous AVP and by plasma levels of AVP that rise normally with increase in plasma osmolality. Hereditary neurohypophyseal diabetes insipidus is secondary to mutations in the gene encoding AVP (OMIM 192340)(1). Neurohypophyseal diabetes insipidus is also a component of autosomal recessive Wolfram syndrome 1 or DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) (OMIM 222300)(1), an autosomal recessive disorder. Other inherited disorders with complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium include Bartter syndrome (OMIM 601678)(1) and cystinosis (OMIM 219800)(1), while long-term lithium administration is the main cause of acquired NDI. Here, we use the gene symbols approved by the HUGO Gene Nomenclature Committee (http://www.gene.ucl.ac.uk/nomenclature) and provide OMIM entry numbers [OMIM (Online Mendelian Inheritance in Man)(1); McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD), 2000; World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/]. Copyright © 2009 Elsevier Inc. All rights reserved.

Publication of nuclear magnetic resonance experimental data with semantic web technology and the application thereof to biomedical research of proteins.

PubMed

Yokochi, Masashi; Kobayashi, Naohiro; Ulrich, Eldon L; Kinjo, Akira R; Iwata, Takeshi; Ioannidis, Yannis E; Livny, Miron; Markley, John L; Nakamura, Haruki; Kojima, Chojiro; Fujiwara, Toshimichi

2016-05-05

The nuclear magnetic resonance (NMR) spectroscopic data for biological macromolecules archived at the BioMagResBank (BMRB) provide a rich resource of biophysical information at atomic resolution. The NMR data archived in NMR-STAR ASCII format have been implemented in a relational database. However, it is still fairly difficult for users to retrieve data from the NMR-STAR files or the relational database in association with data from other biological databases. To enhance the interoperability of the BMRB database, we present a full conversion of BMRB entries to two standard structured data formats, XML and RDF, as common open representations of the NMR-STAR data. Moreover, a SPARQL endpoint has been deployed. The described case study demonstrates that a simple query of the SPARQL endpoints of the BMRB, UniProt, and Online Mendelian Inheritance in Man (OMIM), can be used in NMR and structure-based analysis of proteins combined with information of single nucleotide polymorphisms (SNPs) and their phenotypes. We have developed BMRB/XML and BMRB/RDF and demonstrate their use in performing a federated SPARQL query linking the BMRB to other databases through standard semantic web technologies. This will facilitate data exchange across diverse information resources.

Mining Genotype-Phenotype Associations from Public Knowledge Sources via Semantic Web Querying

PubMed Central

Kiefer, Richard C.; Freimuth, Robert R.; Chute, Christopher G; Pathak, Jyotishman

Gene Wiki Plus (GeneWiki+) and the Online Mendelian Inheritance in Man (OMIM) are publicly available resources for sharing information about disease-gene and gene-SNP associations in humans. While immensely useful to the scientific community, both resources are manually curated, thereby making the data entry and publication process time-consuming, and to some degree, error-prone. To this end, this study investigates Semantic Web technologies to validate existing and potentially discover new genotype-phenotype associations in GWP and OMIM. In particular, we demonstrate the applicability of SPARQL queries for identifying associations not explicitly stated for commonly occurring chronic diseases in GWP and OMIM, and report our preliminary findings for coverage, completeness, and validity of the associations. Our results highlight the benefits of Semantic Web querying technology to validate existing disease-gene associations as well as identify novel associations although further evaluation and analysis is required before such information can be applied and used effectively. PMID:24303249

Pituitary gene mutations and the growth hormone pathway.

PubMed

Moseley, C T; Phillips, J A

2000-01-01

Hereditary forms of pituitary insufficiency not associated with anatomic defects of the central nervous system, hypothalamus, or pituitary are a heterogeneous group of disorders that result from interruptions at different points in the hypothalamic-pituitary-somatomedin-peripheral tissue axis. These different types of pituitary dwarfism can be classified on the level of the defect; mode of inheritance; whether the phenotype is isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD); whether the hormone is absent, deficient, or abnormal; and, in patients with GH resistance, whether insulin-like growth factor 1 (IGF1) is deficient due to GH receptor or IGF1 defects. Information on each disorder is summarized. More detailed information can be obtained through the electronic database Online Mendelian Inheritance in Man which is available at http://www3.ncbi.nlm.nih.gov/Omim/.

Inferring Higher Functional Information for RIKEN Mouse Full-Length cDNA Clones With FACTS

PubMed Central

Nagashima, Takeshi; Silva, Diego G.; Petrovsky, Nikolai; Socha, Luis A.; Suzuki, Harukazu; Saito, Rintaro; Kasukawa, Takeya; Kurochkin, Igor V.; Konagaya, Akihiko; Schönbach, Christian

2003-01-01

FACTS (Functional Association/Annotation of cDNA Clones from Text/Sequence Sources) is a semiautomated knowledge discovery and annotation system that integrates molecular function information derived from sequence analysis results (sequence inferred) with functional information extracted from text. Text-inferred information was extracted from keyword-based retrievals of MEDLINE abstracts and by matching of gene or protein names to OMIM, BIND, and DIP database entries. Using FACTS, we found that 47.5% of the 60,770 RIKEN mouse cDNA FANTOM2 clone annotations were informative for text searches. MEDLINE queries yielded molecular interaction-containing sentences for 23.1% of the clones. When disease MeSH and GO terms were matched with retrieved abstracts, 22.7% of clones were associated with potential diseases, and 32.5% with GO identifiers. A significant number (23.5%) of disease MeSH-associated clones were also found to have a hereditary disease association (OMIM Morbidmap). Inferred neoplastic and nervous system disease represented 49.6% and 36.0% of disease MeSH-associated clones, respectively. A comparison of sequence-based GO assignments with informative text-based GO assignments revealed that for 78.2% of clones, identical GO assignments were provided for that clone by either method, whereas for 21.8% of clones, the assignments differed. In contrast, for OMIM assignments, only 28.5% of clones had identical sequence-based and text-based OMIM assignments. Sequence, sentence, and term-based functional associations are included in the FACTS database (http://facts.gsc.riken.go.jp/), which permits results to be annotated and explored through web-accessible keyword and sequence search interfaces. The FACTS database will be a critical tool for investigating the functional complexity of the mouse transcriptome, cDNA-inferred interactome (molecular interactions), and pathome (pathologies). PMID:12819151

WormQTLHD—a web database for linking human disease to natural variation data in C. elegans

PubMed Central

van der Velde, K. Joeri; de Haan, Mark; Zych, Konrad; Arends, Danny; Snoek, L. Basten; Kammenga, Jan E.; Jansen, Ritsert C.; Swertz, Morris A.; Li, Yang

2014-01-01

Interactions between proteins are highly conserved across species. As a result, the molecular basis of multiple diseases affecting humans can be studied in model organisms that offer many alternative experimental opportunities. One such organism—Caenorhabditis elegans—has been used to produce much molecular quantitative genetics and systems biology data over the past decade. We present WormQTLHD (Human Disease), a database that quantitatively and systematically links expression Quantitative Trait Loci (eQTL) findings in C. elegans to gene–disease associations in man. WormQTLHD, available online at http://www.wormqtl-hd.org, is a user-friendly set of tools to reveal functionally coherent, evolutionary conserved gene networks. These can be used to predict novel gene-to-gene associations and the functions of genes underlying the disease of interest. We created a new database that links C. elegans eQTL data sets to human diseases (34 337 gene–disease associations from OMIM, DGA, GWAS Central and NHGRI GWAS Catalogue) based on overlapping sets of orthologous genes associated to phenotypes in these two species. We utilized QTL results, high-throughput molecular phenotypes, classical phenotypes and genotype data covering different developmental stages and environments from WormQTL database. All software is available as open source, built on MOLGENIS and xQTL workbench. PMID:24217915

WormQTLHD--a web database for linking human disease to natural variation data in C. elegans.

PubMed

van der Velde, K Joeri; de Haan, Mark; Zych, Konrad; Arends, Danny; Snoek, L Basten; Kammenga, Jan E; Jansen, Ritsert C; Swertz, Morris A; Li, Yang

2014-01-01

Interactions between proteins are highly conserved across species. As a result, the molecular basis of multiple diseases affecting humans can be studied in model organisms that offer many alternative experimental opportunities. One such organism-Caenorhabditis elegans-has been used to produce much molecular quantitative genetics and systems biology data over the past decade. We present WormQTL(HD) (Human Disease), a database that quantitatively and systematically links expression Quantitative Trait Loci (eQTL) findings in C. elegans to gene-disease associations in man. WormQTL(HD), available online at http://www.wormqtl-hd.org, is a user-friendly set of tools to reveal functionally coherent, evolutionary conserved gene networks. These can be used to predict novel gene-to-gene associations and the functions of genes underlying the disease of interest. We created a new database that links C. elegans eQTL data sets to human diseases (34 337 gene-disease associations from OMIM, DGA, GWAS Central and NHGRI GWAS Catalogue) based on overlapping sets of orthologous genes associated to phenotypes in these two species. We utilized QTL results, high-throughput molecular phenotypes, classical phenotypes and genotype data covering different developmental stages and environments from WormQTL database. All software is available as open source, built on MOLGENIS and xQTL workbench.

SIDD: A Semantically Integrated Database towards a Global View of Human Disease

PubMed Central

Cheng, Liang; Wang, Guohua; Li, Jie; Zhang, Tianjiao; Xu, Peigang; Wang, Yadong

2013-01-01

Background A number of databases have been developed to collect disease-related molecular, phenotypic and environmental features (DR-MPEs), such as genes, non-coding RNAs, genetic variations, drugs, phenotypes and environmental factors. However, each of current databases focused on only one or two DR-MPEs. There is an urgent demand to develop an integrated database, which can establish semantic associations among disease-related databases and link them to provide a global view of human disease at the biological level. This database, once developed, will facilitate researchers to query various DR-MPEs through disease, and investigate disease mechanisms from different types of data. Methodology To establish an integrated disease-associated database, disease vocabularies used in different databases are mapped to Disease Ontology (DO) through semantic match. 4,284 and 4,186 disease terms from Medical Subject Headings (MeSH) and Online Mendelian Inheritance in Man (OMIM) respectively are mapped to DO. Then, the relationships between DR-MPEs and diseases are extracted and merged from different source databases for reducing the data redundancy. Conclusions A semantically integrated disease-associated database (SIDD) is developed, which integrates 18 disease-associated databases, for researchers to browse multiple types of DR-MPEs in a view. A web interface allows easy navigation for querying information through browsing a disease ontology tree or searching a disease term. Furthermore, a network visualization tool using Cytoscape Web plugin has been implemented in SIDD. It enhances the SIDD usage when viewing the relationships between diseases and DR-MPEs. The current version of SIDD (Jul 2013) documents 4,465,131 entries relating to 139,365 DR-MPEs, and to 3,824 human diseases. The database can be freely accessed from: http://mlg.hit.edu.cn/SIDD. PMID:24146757

Clique-based data mining for related genes in a biomedical database.

PubMed

Matsunaga, Tsutomu; Yonemori, Chikara; Tomita, Etsuji; Muramatsu, Masaaki

2009-07-01

Progress in the life sciences cannot be made without integrating biomedical knowledge on numerous genes in order to help formulate hypotheses on the genetic mechanisms behind various biological phenomena, including diseases. There is thus a strong need for a way to automatically and comprehensively search from biomedical databases for related genes, such as genes in the same families and genes encoding components of the same pathways. Here we address the extraction of related genes by searching for densely-connected subgraphs, which are modeled as cliques, in a biomedical relational graph. We constructed a graph whose nodes were gene or disease pages, and edges were the hyperlink connections between those pages in the Online Mendelian Inheritance in Man (OMIM) database. We obtained over 20,000 sets of related genes (called 'gene modules') by enumerating cliques computationally. The modules included genes in the same family, genes for proteins that form a complex, and genes for components of the same signaling pathway. The results of experiments using 'metabolic syndrome'-related gene modules show that the gene modules can be used to get a coherent holistic picture helpful for interpreting relations among genes. We presented a data mining approach extracting related genes by enumerating cliques. The extracted gene sets provide a holistic picture useful for comprehending complex disease mechanisms.

The status of online Mendelian inheritance in man (OMIM) medio 1994.

PubMed Central

Pearson, P; Francomano, C; Foster, P; Bocchini, C; Li, P; McKusick, V

1994-01-01

During the last year many changes have been introduced into the system of maintaining OMIM. There are three major components of the reorganization. First, a distributed editorial system was introduced which provides a three-tiered editorial board with senior editors, science writers and subject editors. Second, MIM entries have been restructured to provide separate gene and phenotype information and to organize them into separate catalogs. The restructuring also establishes clearly defined sections for entering new information, converts old entries to the new structure, and establishes a file maintenance and editorial system in SGML format. Third, the entry numbering and naming system has been modified. In addition, the information has been made available through a variety of output media, including books, CD-ROM and online access based on the IRx, WAIS, Gopher and WWW formats. PMID:7937048

Resources for comparing the speed and performance of medical autocoders.

PubMed

Berman, Jules J

2004-06-15

Concept indexing is a popular method for characterizing medical text, and is one of the most important early steps in many data mining efforts. Concept indexing differs from simple word or phrase indexing because concepts are typically represented by a nomenclature code that binds a medical concept to all equivalent representations. A concept search on the term renal cell carcinoma would be expected to find occurrences of hypernephroma, and renal carcinoma (concept equivalents). The purpose of this study is to provide freely available resources to compare speed and performance among different autocoders. These tools consist of: 1) a public domain autocoder written in Perl (a free and open source programming language that installs on any operating system); 2) a nomenclature database derived from the unencumbered subset of the publicly available Unified Medical Language System; 3) a large corpus of autocoded output derived from a publicly available medical text. A simple lexical autocoder was written that parses plain-text into a listing of all 1,2,3, and 4-word strings contained in text, assigning a nomenclature code for text strings that match terms in the nomenclature. The nomenclature used is the unencumbered subset of the 2003 Unified Medical Language System (UMLS). The unencumbered subset of UMLS was reduced to exclude homonymous one-word terms and proper names, resulting in a term/code data dictionary containing about a half million medical terms. The Online Mendelian Inheritance in Man (OMIM), a 92+ Megabyte publicly available medical opus, was used as sample medical text for the autocoder. The autocoding Perl script is remarkably short, consisting of just 38 command lines. The 92+ Megabyte OMIM file was completely autocoded in 869 seconds on a 2.4 GHz processor (less than 10 seconds per Megabyte of text). The autocoded output file (9,540,442 bytes) contains 367,963 coded terms from OMIM and is distributed with this manuscript. A public domain Perl script is provided that can parse through plain-text files of any length, matching concepts against an external nomenclature. The script and associated files can be used freely to compare the speed and performance of autocoding software.

Deciphering the Relationship between Obesity and Various Diseases from a Network Perspective

PubMed Central

Zhang, Yu-Hang; Wang, ShaoPeng; Zhang, YunHua

2017-01-01

The number of obesity cases is rapidly increasing in developed and developing countries, thereby causing significant health problems worldwide. The pathologic factors of obesity at the molecular level are not fully characterized, although the imbalance between energy intake and consumption is widely recognized as the main reason for fat accumulation. Previous studies reported that obesity can be caused by the dysfunction of genes associated with other diseases, such as myocardial infarction, hence providing new insights into dissecting the pathogenesis of obesity by investigating its associations with other diseases. In this study, we investigated the relationship between obesity and diseases from Online Mendelian Inheritance in Man (OMIM) databases on the protein–protein interaction (PPI) network. The obesity genes and genes of one OMIM disease were mapped onto the network, and the interaction scores between the two gene sets were investigated on the basis of the PPI of individual gene pairs, thereby inferring the relationship between obesity and this disease. Results suggested that diseases related to nutrition and endocrine are the top two diseases that are closely associated with obesity. This finding is consistent with our general knowledge and indicates the reliability of our obtained results. Moreover, we inferred that diseases related to psychiatric factors and bone may also be highly related to obesity because the two diseases followed the diseases related to nutrition and endocrine according to our results. Numerous obesity–disease associations were identified in the literature to confirm the relationships between obesity and the aforementioned four diseases. These new results may help understand the underlying molecular mechanisms of obesity–disease co-occurrence and provide useful insights for disease prevention and intervention. PMID:29258237

Glycogen debranching enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide pyrophosphatase 2 (ENPP2_1), glutathione S-transferase 3 (GSTM3_3) and mannosidase (MAN2B2) metabolism computational network analysis between chimpanzee and human left cerebrum.

PubMed

Sun, Lingjun; Wang, Lin; Jiang, Minghu; Huang, Juxiang; Lin, Hong

2011-12-01

We identified significantly higher expression of the genes glycogen debranching enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide pyrophosphatase 2 (ENPP2_1), glutathione S-transferase 3 (GSTM3_3) and mannosidase (MAN2B2) from human left cerebrums versus chimpanzees. Yet the distinct low- and high-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism networks between chimpanzee and human left cerebrum remain to be elucidated. Here, we constructed low- and high-expression activated and inhibited upstream and downstream AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network between chimpanzee and human left cerebrum in GEO data set by gene regulatory network inference method based on linear programming and decomposition procedure, under covering AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 pathway and matching metabolism enrichment analysis by CapitalBio MAS 3.0 integration of public databases, including Gene Ontology, KEGG, BioCarta, GenMapp, Intact, UniGene, OMIM, etc. Our results show that the AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network has more activated and less inhibited molecules in chimpanzee, but less activated and more inhibited in the human left cerebrum. We inferred stronger carbohydrate, glutathione and proteoglycan metabolism, ATPase activity, but weaker base excision repair, arachidonic acid and drug metabolism as a result of inducing cell growth in low-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network of chimpanzee left cerebrum; whereas stronger lipid metabolism, amino acid catabolism, DNA repair but weaker inflammatory response, cell proliferation, glutathione and carbohydrate metabolism as a result of inducing cell differentiation in high-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network of human left cerebrum. Our inferences are consistent with recent reports and computational activation and inhibition gene number patterns, respectively.

Assessing toxic effects of [Omim]Cl and [Omim]BF4 in zebrafish adults using a biomarker approach.

PubMed

Liu, Tong; Guo, Yingying; Wang, Jinhua; Wang, Jun; Zhu, Lusheng; Zhang, Jun; Zhang, Cheng

2016-04-01

In the present study, the toxic effects of 1-octyl-3-methylimidazolium chloride ([Omim]Cl) and 1-octyl-3-methylimidazolium tetrafluoroborate ([Omim]BF4) on the zebrafish livers were studied at 0, 5, 10, 20, and 40 mg L(-1) on the 7th and 14th days. In addition, the concentrations of [Omim]Cl and [Omim]BF4 in the test water, the acute toxicity of the two ionic liquids (ILs), and the influence of anions on the toxicity of the ILs were evaluated. The acute toxicity test results showed 50 % lethal concentration (LC50) values of 152.3 ± 12.1 mg L(-1) for [Omim]Cl and 144.0 ± 11.4 mg L(-1) for [Omim]BF4. At the lowest concentration investigated (5 mg L(-1)), [Omim]Cl and [Omim]BF4 did not significantly affect zebrafish during the exposure period. However, the toxic effects of these substances were enhanced as dosing concentrations and exposure times were increased. Levels of reactive oxygen species (ROS) were significantly enhanced on the 7th day after 20 mg L(-1) and on the 14th day after 10 mg L(-1) of either substance was applied, resulting in oxidative damage, such as lipid peroxidation and DNA damage. The experimental results also indicated little effect of the anions on the toxicity of ILs and consistent toxic effects of [Omim]Cl and [Omim]BF4. Graphical Abstract The graphical abstract for the present study after exposure to [Omim]Cl and [Omim]BF4. The letter R represents the anions Cl(-) and BF4 (.)

Functional insights from the distribution and role of homopeptide repeat-containing proteins

PubMed Central

Faux, Noel G.; Bottomley, Stephen P.; Lesk, Arthur M.; Irving, James A.; Morrison, John R.; de la Banda, Maria Garcia; Whisstock, James C.

2005-01-01

Expansion of “low complex” repeats of amino acids such as glutamine (Poly-Q) is associated with protein misfolding and the development of degenerative diseases such as Huntington's disease. The mechanism by which such regions promote misfolding remains controversial, the function of many repeat-containing proteins (RCPs) remains obscure, and the role (if any) of repeat regions remains to be determined. Here, a Web-accessible database of RCPs is presented. The distribution and evolution of RCPs that contain homopeptide repeats tracts are considered, and the existence of functional patterns investigated. Generally, it is found that while polyamino acid repeats are extremely rare in prokaryotes, several eukaryote putative homologs of prokaryote RCP—involved in important housekeeping processes—retain the repetitive region, suggesting an ancient origin for certain repeats. Within eukarya, the most common uninterrupted amino acid repeats are glutamine, asparagines, and alanine. Interestingly, while poly-Q repeats are found in vertebrates and nonvertebrates, poly-N repeats are only common in more primitive nonvertebrate organisms, such as insects and nematodes. We have assigned function to eukaryote RCPs using Online Mendelian Inheritance in Man (OMIM), the Human Reference Protein Database (HRPD), FlyBase, and Wormpep. Prokaryote RCPs were annotated using BLASTp searches and Gene Ontology. These data reveal that the majority of RCPs are involved in processes that require the assembly of large, multiprotein complexes, such as transcription and signaling. PMID:15805494

BIOSPIDA: A Relational Database Translator for NCBI.

PubMed

Hagen, Matthew S; Lee, Eva K

2010-11-13

As the volume and availability of biological databases continue widespread growth, it has become increasingly difficult for research scientists to identify all relevant information for biological entities of interest. Details of nucleotide sequences, gene expression, molecular interactions, and three-dimensional structures are maintained across many different databases. To retrieve all necessary information requires an integrated system that can query multiple databases with minimized overhead. This paper introduces a universal parser and relational schema translator that can be utilized for all NCBI databases in Abstract Syntax Notation (ASN.1). The data models for OMIM, Entrez-Gene, Pubmed, MMDB and GenBank have been successfully converted into relational databases and all are easily linkable helping to answer complex biological questions. These tools facilitate research scientists to locally integrate databases from NCBI without significant workload or development time.

Exploring supervised and unsupervised methods to detect topics in biomedical text

PubMed Central

Lee, Minsuk; Wang, Weiqing; Yu, Hong

2006-01-01

Background Topic detection is a task that automatically identifies topics (e.g., "biochemistry" and "protein structure") in scientific articles based on information content. Topic detection will benefit many other natural language processing tasks including information retrieval, text summarization and question answering; and is a necessary step towards the building of an information system that provides an efficient way for biologists to seek information from an ocean of literature. Results We have explored the methods of Topic Spotting, a task of text categorization that applies the supervised machine-learning technique naïve Bayes to assign automatically a document into one or more predefined topics; and Topic Clustering, which apply unsupervised hierarchical clustering algorithms to aggregate documents into clusters such that each cluster represents a topic. We have applied our methods to detect topics of more than fifteen thousand of articles that represent over sixteen thousand entries in the Online Mendelian Inheritance in Man (OMIM) database. We have explored bag of words as the features. Additionally, we have explored semantic features; namely, the Medical Subject Headings (MeSH) that are assigned to the MEDLINE records, and the Unified Medical Language System (UMLS) semantic types that correspond to the MeSH terms, in addition to bag of words, to facilitate the tasks of topic detection. Our results indicate that incorporating the MeSH terms and the UMLS semantic types as additional features enhances the performance of topic detection and the naïve Bayes has the highest accuracy, 66.4%, for predicting the topic of an OMIM article as one of the total twenty-five topics. Conclusion Our results indicate that the supervised topic spotting methods outperformed the unsupervised topic clustering; on the other hand, the unsupervised topic clustering methods have the advantages of being robust and applicable in real world settings. PMID:16539745

Inductive matrix completion for predicting gene-disease associations.

PubMed

Natarajan, Nagarajan; Dhillon, Inderjit S

2014-06-15

Most existing methods for predicting causal disease genes rely on specific type of evidence, and are therefore limited in terms of applicability. More often than not, the type of evidence available for diseases varies-for example, we may know linked genes, keywords associated with the disease obtained by mining text, or co-occurrence of disease symptoms in patients. Similarly, the type of evidence available for genes varies-for example, specific microarray probes convey information only for certain sets of genes. In this article, we apply a novel matrix-completion method called Inductive Matrix Completion to the problem of predicting gene-disease associations; it combines multiple types of evidence (features) for diseases and genes to learn latent factors that explain the observed gene-disease associations. We construct features from different biological sources such as microarray expression data and disease-related textual data. A crucial advantage of the method is that it is inductive; it can be applied to diseases not seen at training time, unlike traditional matrix-completion approaches and network-based inference methods that are transductive. Comparison with state-of-the-art methods on diseases from the Online Mendelian Inheritance in Man (OMIM) database shows that the proposed approach is substantially better-it has close to one-in-four chance of recovering a true association in the top 100 predictions, compared to the recently proposed Catapult method (second best) that has <15% chance. We demonstrate that the inductive method is particularly effective for a query disease with no previously known gene associations, and for predicting novel genes, i.e. genes that are previously not linked to diseases. Thus the method is capable of predicting novel genes even for well-characterized diseases. We also validate the novelty of predictions by evaluating the method on recently reported OMIM associations and on associations recently reported in the literature. Source code and datasets can be downloaded from http://bigdata.ices.utexas.edu/project/gene-disease. © The Author 2014. Published by Oxford University Press.

BIOSPIDA: A Relational Database Translator for NCBI

PubMed Central

Hagen, Matthew S.; Lee, Eva K.

2010-01-01

As the volume and availability of biological databases continue widespread growth, it has become increasingly difficult for research scientists to identify all relevant information for biological entities of interest. Details of nucleotide sequences, gene expression, molecular interactions, and three-dimensional structures are maintained across many different databases. To retrieve all necessary information requires an integrated system that can query multiple databases with minimized overhead. This paper introduces a universal parser and relational schema translator that can be utilized for all NCBI databases in Abstract Syntax Notation (ASN.1). The data models for OMIM, Entrez-Gene, Pubmed, MMDB and GenBank have been successfully converted into relational databases and all are easily linkable helping to answer complex biological questions. These tools facilitate research scientists to locally integrate databases from NCBI without significant workload or development time. PMID:21347013

Atlas - a data warehouse for integrative bioinformatics.

PubMed

Shah, Sohrab P; Huang, Yong; Xu, Tao; Yuen, Macaire M S; Ling, John; Ouellette, B F Francis

2005-02-21

We present a biological data warehouse called Atlas that locally stores and integrates biological sequences, molecular interactions, homology information, functional annotations of genes, and biological ontologies. The goal of the system is to provide data, as well as a software infrastructure for bioinformatics research and development. The Atlas system is based on relational data models that we developed for each of the source data types. Data stored within these relational models are managed through Structured Query Language (SQL) calls that are implemented in a set of Application Programming Interfaces (APIs). The APIs include three languages: C++, Java, and Perl. The methods in these API libraries are used to construct a set of loader applications, which parse and load the source datasets into the Atlas database, and a set of toolbox applications which facilitate data retrieval. Atlas stores and integrates local instances of GenBank, RefSeq, UniProt, Human Protein Reference Database (HPRD), Biomolecular Interaction Network Database (BIND), Database of Interacting Proteins (DIP), Molecular Interactions Database (MINT), IntAct, NCBI Taxonomy, Gene Ontology (GO), Online Mendelian Inheritance in Man (OMIM), LocusLink, Entrez Gene and HomoloGene. The retrieval APIs and toolbox applications are critical components that offer end-users flexible, easy, integrated access to this data. We present use cases that use Atlas to integrate these sources for genome annotation, inference of molecular interactions across species, and gene-disease associations. The Atlas biological data warehouse serves as data infrastructure for bioinformatics research and development. It forms the backbone of the research activities in our laboratory and facilitates the integration of disparate, heterogeneous biological sources of data enabling new scientific inferences. Atlas achieves integration of diverse data sets at two levels. First, Atlas stores data of similar types using common data models, enforcing the relationships between data types. Second, integration is achieved through a combination of APIs, ontology, and tools. The Atlas software is freely available under the GNU General Public License at: http://bioinformatics.ubc.ca/atlas/

Atlas – a data warehouse for integrative bioinformatics

PubMed Central

Shah, Sohrab P; Huang, Yong; Xu, Tao; Yuen, Macaire MS; Ling, John; Ouellette, BF Francis

2005-01-01

Background We present a biological data warehouse called Atlas that locally stores and integrates biological sequences, molecular interactions, homology information, functional annotations of genes, and biological ontologies. The goal of the system is to provide data, as well as a software infrastructure for bioinformatics research and development. Description The Atlas system is based on relational data models that we developed for each of the source data types. Data stored within these relational models are managed through Structured Query Language (SQL) calls that are implemented in a set of Application Programming Interfaces (APIs). The APIs include three languages: C++, Java, and Perl. The methods in these API libraries are used to construct a set of loader applications, which parse and load the source datasets into the Atlas database, and a set of toolbox applications which facilitate data retrieval. Atlas stores and integrates local instances of GenBank, RefSeq, UniProt, Human Protein Reference Database (HPRD), Biomolecular Interaction Network Database (BIND), Database of Interacting Proteins (DIP), Molecular Interactions Database (MINT), IntAct, NCBI Taxonomy, Gene Ontology (GO), Online Mendelian Inheritance in Man (OMIM), LocusLink, Entrez Gene and HomoloGene. The retrieval APIs and toolbox applications are critical components that offer end-users flexible, easy, integrated access to this data. We present use cases that use Atlas to integrate these sources for genome annotation, inference of molecular interactions across species, and gene-disease associations. Conclusion The Atlas biological data warehouse serves as data infrastructure for bioinformatics research and development. It forms the backbone of the research activities in our laboratory and facilitates the integration of disparate, heterogeneous biological sources of data enabling new scientific inferences. Atlas achieves integration of diverse data sets at two levels. First, Atlas stores data of similar types using common data models, enforcing the relationships between data types. Second, integration is achieved through a combination of APIs, ontology, and tools. The Atlas software is freely available under the GNU General Public License at: PMID:15723693

HypoxiaDB: a database of hypoxia-regulated proteins

PubMed Central

Khurana, Pankaj; Sugadev, Ragumani; Jain, Jaspreet; Singh, Shashi Bala

2013-01-01

There has been intense interest in the cellular response to hypoxia, and a large number of differentially expressed proteins have been identified through various high-throughput experiments. These valuable data are scattered, and there have been no systematic attempts to document the various proteins regulated by hypoxia. Compilation, curation and annotation of these data are important in deciphering their role in hypoxia and hypoxia-related disorders. Therefore, we have compiled HypoxiaDB, a database of hypoxia-regulated proteins. It is a comprehensive, manually-curated, non-redundant catalog of proteins whose expressions are shown experimentally to be altered at different levels and durations of hypoxia. The database currently contains 72 000 manually curated entries taken on 3500 proteins extracted from 73 peer-reviewed publications selected from PubMed. HypoxiaDB is distinctive from other generalized databases: (i) it compiles tissue-specific protein expression changes under different levels and duration of hypoxia. Also, it provides manually curated literature references to support the inclusion of the protein in the database and establish its association with hypoxia. (ii) For each protein, HypoxiaDB integrates data on gene ontology, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, protein–protein interactions, protein family (Pfam), OMIM (Online Mendelian Inheritance in Man), PDB (Protein Data Bank) structures and homology to other sequenced genomes. (iii) It also provides pre-compiled information on hypoxia-proteins, which otherwise requires tedious computational analysis. This includes information like chromosomal location, identifiers like Entrez, HGNC, Unigene, Uniprot, Ensembl, Vega, GI numbers and Genbank accession numbers associated with the protein. These are further cross-linked to respective public databases augmenting HypoxiaDB to the external repositories. (iv) In addition, HypoxiaDB provides an online sequence-similarity search tool for users to compare their protein sequences with HypoxiaDB protein database. We hope that HypoxiaDB will enrich our knowledge about hypoxia-related biology and eventually will lead to the development of novel hypothesis and advancements in diagnostic and therapeutic activities. HypoxiaDB is freely accessible for academic and non-profit users via http://www.hypoxiadb.com. Database URL: http://www.hypoxiadb.com PMID:24178989

Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko

2010-08-19

Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene couldmore » be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding techniques for fine mapping of breakpoints in papillary thyroid cancer (PTC).« less

The Nuclear Protein Database (NPD): sub-nuclear localisation and functional annotation of the nuclear proteome

PubMed Central

Dellaire, G.; Farrall, R.; Bickmore, W.A.

2003-01-01

The Nuclear Protein Database (NPD) is a curated database that contains information on more than 1300 vertebrate proteins that are thought, or are known, to localise to the cell nucleus. Each entry is annotated with information on predicted protein size and isoelectric point, as well as any repeats, motifs or domains within the protein sequence. In addition, information on the sub-nuclear localisation of each protein is provided and the biological and molecular functions are described using Gene Ontology (GO) terms. The database is searchable by keyword, protein name, sub-nuclear compartment and protein domain/motif. Links to other databases are provided (e.g. Entrez, SWISS-PROT, OMIM, PubMed, PubMed Central). Thus, NPD provides a gateway through which the nuclear proteome may be explored. The database can be accessed at http://npd.hgu.mrc.ac.uk and is updated monthly. PMID:12520015

PhenoTips: patient phenotyping software for clinical and research use.

PubMed

Girdea, Marta; Dumitriu, Sergiu; Fiume, Marc; Bowdin, Sarah; Boycott, Kym M; Chénier, Sébastien; Chitayat, David; Faghfoury, Hanna; Meyn, M Stephen; Ray, Peter N; So, Joyce; Stavropoulos, Dimitri J; Brudno, Michael

2013-08-01

We have developed PhenoTips: open source software for collecting and analyzing phenotypic information for patients with genetic disorders. Our software combines an easy-to-use interface, compatible with any device that runs a Web browser, with a standardized database back end. The PhenoTips' user interface closely mirrors clinician workflows so as to facilitate the recording of observations made during the patient encounter. Collected data include demographics, medical history, family history, physical and laboratory measurements, physical findings, and additional notes. Phenotypic information is represented using the Human Phenotype Ontology; however, the complexity of the ontology is hidden behind a user interface, which combines simple selection of common phenotypes with error-tolerant, predictive search of the entire ontology. PhenoTips supports accurate diagnosis by analyzing the entered data, then suggesting additional clinical investigations and providing Online Mendelian Inheritance in Man (OMIM) links to likely disorders. By collecting, classifying, and analyzing phenotypic information during the patient encounter, PhenoTips allows for streamlining of clinic workflow, efficient data entry, improved diagnosis, standardization of collected patient phenotypes, and sharing of anonymized patient phenotype data for the study of rare disorders. Our source code and a demo version of PhenoTips are available at http://phenotips.org. © 2013 WILEY PERIODICALS, INC.

Orofacial manifestations of achondroplasia

PubMed Central

Rohilla, Smriti; Kaushik, Atul; Vinod, V.C.; Tanwar, Renu; Kumar, Munish

2012-01-01

Achondroplasia (Online Mendelian Inheritance in Man [OMIM] 100800), is considered as a form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of special interest in the field of dentistry because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control requires special precautions during dental management. The current case report highlights the orofacial manifestations of Achondroplasia in a young pediatric patient, along with the multidisciplinary treatment (including the dental treatment) done for the patient which also might help the general practitioners in better understanding of the condition. PMID:27298609

Management and analysis of genomic functional and phenotypic controlled annotations to support biomedical investigation and practice.

PubMed

Masseroli, Marco

2007-07-01

The growing available genomic information provides new opportunities for novel research approaches and original biomedical applications that can provide effective data management and analysis support. In fact, integration and comprehensive evaluation of available controlled data can highlight information patterns leading to unveil new biomedical knowledge. Here, we describe Genome Function INtegrated Discover (GFINDer), a Web-accessible three-tier multidatabase system we developed to automatically enrich lists of user-classified genes with several functional and phenotypic controlled annotations, and to statistically evaluate them in order to identify annotation categories significantly over- or underrepresented in each considered gene class. Genomic controlled annotations from Gene Ontology (GO), KEGG, Pfam, InterPro, and Online Mendelian Inheritance in Man (OMIM) were integrated in GFINDer and several categorical tests were implemented for their analysis. A controlled vocabulary of inherited disorder phenotypes was obtained by normalizing and hierarchically structuring disease accompanying signs and symptoms from OMIM Clinical Synopsis sections. GFINDer modular architecture is well suited for further system expansion and for sustaining increasing workload. Testing results showed that GFINDer analyses can highlight gene functional and phenotypic characteristics and differences, demonstrating its value in supporting genomic biomedical approaches aiming at understanding the complex biomolecular mechanisms underlying patho-physiological phenotypes, and in helping the transfer of genomic results to medical practice.

Three degradation pathways of 1-octyl-3-methylimidazolium cation by activated sludge from wastewater treatment process.

PubMed

Cho, Chul-Woong; Pham, Thi Phuong Thuy; Kim, Sok; Song, Myung-Hee; Chung, Yun-Jo; Yun, Yeoung-Sang

2016-03-01

The biodegradability and degradation pathways of 1-octyl-3-methylimidazolium cation [OMIM](+) by microbial community of wastewater treatment plant in Jeonju city, Korea were investigated. It was found that [OMIM](+) could be easily degraded by the microbial community. New degradation products and pathways of [OMIM](+) were identified, which are partially different from previous results (Green Chem. 2008, 10, 214-224). For the analysis of the degradation pathways and intermediates, the mass peaks observed in the range m/z of 50-300 were screened by using a tandem mass spectrometer (MS), and their fragmentation patterns were investigated by MS/MS. Surprisingly, we found three different degradation pathways of [OMIM](+), which were separated according to the initially oxidized position i.e. middle of the long alkyl chain, end of the long alkyl chain, and end of the short alkyl chain. The degradation pathways showed that the long and short alkyl chains of [OMIM](+) gradually degraded by repeating oxidation and carbon release. The results presented here shows that [OMIM](+) can be easily biodegraded through three different degradation pathways in wastewater treatment plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of phosphatidylinositol-3-OH-kinase (PI3-kinase) and respiratory burst enzymes in the [omim][BF4]-mediated toxic mode of action in mussel hemocytes.

PubMed

Belavgeni, Alexia; Dailianis, Stefanos

2017-09-01

The present study investigates the role of phosphatidylinositol-3-OH-kinase (PI3-kinase) and respiratory burst enzymes, NADPH oxidase and NO synthase, in the 1-methyl-3-octylimidazolium tetrafluoroborate ([omim][BF 4 ])-mediated toxic mode of action in mussel hemocytes. Specifically, cell viability (using the neutral red uptake assay) was primarily tested in hemocytes treated with different concentrations of [omim][BF 4 ] (0.1-10 mg L -1 ) and thereafter [omim][BF 4 ]-mediated oxidative (in terms of superoxide anions/O 2 - and nitric oxide/NO generation, as well as the enhancement of lipid peroxidation by-products, in terms of malondialdehyde/MDA) and genotoxic (in terms of DNA damage) effects were determined in hemocytes treated with 1 mg L -1 [omim][BF 4 ]. Moreover, in order to investigate, even indirectly and non-entirely specific, the role of PI3-kinase, NADPH oxidase and NO synthase, the [omim][BF 4 ]-mediated effects were also investigated in hemocytes pre-incubated with wortmannin (50 nM), diphenyleneiodonium chloride (DPI 10 μM) and N G -nitro- l -arginine methyl ester (l-NAME 10 μM), respectively. The results showed that [omim][BF 4 ] ability to enhance O 2 - , NO, MDA and DNA damage, via its interaction with cellular membranes, was significantly attenuated in the presence of each inhibitor in almost all cases. The current findings revealed for the first time that certain signaling molecules, such as PI3-kinase, as well as respiratory burst enzymes activation, such as NADPH oxidase and NO synthase, could merely attribute to the [omim][BF 4 ]-mediated mode of action, thus enriching our knowledge for the molecular mechanisms of ILs toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mimvec: a deep learning approach for analyzing the human phenome.

PubMed

Gan, Mingxin; Li, Wenran; Zeng, Wanwen; Wang, Xiaojian; Jiang, Rui

2017-09-21

The human phenome has been widely used with a variety of genomic data sources in the inference of disease genes. However, most existing methods thus far derive phenotype similarity based on the analysis of biomedical databases by using the traditional term frequency-inverse document frequency (TF-IDF) formulation. This framework, though intuitive, not only ignores semantic relationships between words but also tends to produce high-dimensional vectors, and hence lacks the ability to precisely capture intrinsic semantic characteristics of biomedical documents. To overcome these limitations, we propose a framework called mimvec to analyze the human phenome by making use of the state-of-the-art deep learning technique in natural language processing. We converted 24,061 records in the Online Mendelian Inheritance in Man (OMIM) database to low-dimensional vectors using our method. We demonstrated that the vector presentation not only effectively enabled classification of phenotype records against gene ones, but also succeeded in discriminating diseases of different inheritance styles and different mechanisms. We further derived pairwise phenotype similarities between 7988 human inherited diseases using their vector presentations. With a joint analysis of this phenome with multiple genomic data, we showed that phenotype overlap indeed implied genotype overlap. We finally used the derived phenotype similarities with genomic data to prioritize candidate genes and demonstrated advantages of this method over existing ones. Our method is capable of not only capturing semantic relationships between words in biomedical records but also alleviating the dimensional disaster accompanying the traditional TF-IDF framework. With the approaching of precision medicine, there will be abundant electronic records of medicine and health awaiting for deep analysis, and we expect to see a wide spectrum of applications borrowing the idea of our method in the near future.

Enabling online studies of conceptual relationships between medical terms: developing an efficient web platform.

PubMed

Albin, Aaron; Ji, Xiaonan; Borlawsky, Tara B; Ye, Zhan; Lin, Simon; Payne, Philip Ro; Huang, Kun; Xiang, Yang

2014-10-07

The Unified Medical Language System (UMLS) contains many important ontologies in which terms are connected by semantic relations. For many studies on the relationships between biomedical concepts, the use of transitively associated information from ontologies and the UMLS has been shown to be effective. Although there are a few tools and methods available for extracting transitive relationships from the UMLS, they usually have major restrictions on the length of transitive relations or on the number of data sources. Our goal was to design an efficient online platform that enables efficient studies on the conceptual relationships between any medical terms. To overcome the restrictions of available methods and to facilitate studies on the conceptual relationships between medical terms, we developed a Web platform, onGrid, that supports efficient transitive queries and conceptual relationship studies using the UMLS. This framework uses the latest technique in converting natural language queries into UMLS concepts, performs efficient transitive queries, and visualizes the result paths. It also dynamically builds a relationship matrix for two sets of input biomedical terms. We are thus able to perform effective studies on conceptual relationships between medical terms based on their relationship matrix. The advantage of onGrid is that it can be applied to study any two sets of biomedical concept relations and the relations within one set of biomedical concepts. We use onGrid to study the disease-disease relationships in the Online Mendelian Inheritance in Man (OMIM). By crossvalidating our results with an external database, the Comparative Toxicogenomics Database (CTD), we demonstrated that onGrid is effective for the study of conceptual relationships between medical terms. onGrid is an efficient tool for querying the UMLS for transitive relations, studying the relationship between medical terms, and generating hypotheses.

[A novel mutation in KCNB1 gene in a child with neuropsychiatric comorbidities with both intellectual disability and epilepsy and review of literature].

PubMed

Miao, P; Peng, J; Chen, C; Gai, N; Yin, F

2017-02-02

Objective: To explore the association between the phenotype and KCNB1 gene mutation. Method: Clinical information including physical features, laboratory and genetic data of one patient of mental retardation with refractory epilepsy from Department of Pediatrics, Xiangya Hospital in January 2016 was analyzed. This patient was discovered to have KCNB1 gene mutations through whole exome sequencing. Relevant information about KCNB1 gene mutation was searched and collected from Pubmed, CNKI, Human Gene Mutation Database(HGMD) and Online Mendelian Inheritance in Man(OMIM). Searching was done using "KCNB1" as a keyword. Result: A 3.5 years old boy who visited our hospital firstly at the age of 2 years because of development delay came for follow up as he developed seizures.The forms included tonic, clonic seizures and spasm. The condition became more severe 10 months later. Electroencephalogram(EEG) showed high frequency discharge (>85%). He had poor response to multiple anti-epileptic drugs, methylprednisolone and ketogenic diet. At the age of 3, he started to have mental regression. Whole exome-sequencing study (trios) identified a novel heterozygous mutation c. G1136T (p.G379V) in KCNB1, which is not available in the databases mentioned above. This is the first case report of KCNB1 gene mutation in China. Eight cases have been reported so far worldwide and all of them were diagnosed with refractory epilepsy. Those 8 reported cases of encephalopathy were all due to de novo mutation. Conclusion: The main clinical features of patients with KCNB1 mutations include severe to profound intellectual disability, intractable seizures, hypotonia and regression of cognition and motor activity which lead to poor prognosis.

Parkinson's disease candidate gene prioritization based on expression profile of midbrain dopaminergic neurons

PubMed Central

2010-01-01

Background Parkinson's disease is the second most common neurodegenerative disorder. The pathological hallmark of the disease is degeneration of midbrain dopaminergic neurons. Genetic association studies have linked 13 human chromosomal loci to Parkinson's disease. Identification of gene(s), as part of the etiology of Parkinson's disease, within the large number of genes residing in these loci can be achieved through several approaches, including screening methods, and considering appropriate criteria. Since several of the indentified Parkinson's disease genes are expressed in substantia nigra pars compact of the midbrain, expression within the neurons of this area could be a suitable criterion to limit the number of candidates and identify PD genes. Methods In this work we have used the combination of findings from six rodent transcriptome analysis studies on the gene expression profile of midbrain dopaminergic neurons and the PARK loci in OMIM (Online Mendelian Inheritance in Man) database, to identify new candidate genes for Parkinson's disease. Results Merging the two datasets, we identified 20 genes within PARK loci, 7 of which are located in an orphan Parkinson's disease locus and one, which had been identified as a disease gene. In addition to identifying a set of candidates for further genetic association studies, these results show that the criteria of expression in midbrain dopaminergic neurons may be used to narrow down the number of genes in PARK loci for such studies. PMID:20716345

Genetic architecture for human aggression: A study of gene-phenotype relationship in OMIM.

PubMed

Zhang-James, Yanli; Faraone, Stephen V

2016-07-01

Genetic studies of human aggression have mainly focused on known candidate genes and pathways regulating serotonin and dopamine signaling and hormonal functions. These studies have taught us much about the genetics of human aggression, but no genetic locus has yet achieved genome-significance. We here present a review based on a paradoxical hypothesis that studies of rare, functional genetic variations can lead to a better understanding of the molecular mechanisms underlying complex multifactorial disorders such as aggression. We examined all aggression phenotypes catalogued in Online Mendelian Inheritance in Man (OMIM), an Online Catalog of Human Genes and Genetic Disorders. We identified 95 human disorders that have documented aggressive symptoms in at least one individual with a well-defined genetic variant. Altogether, we retrieved 86 causal genes. Although most of these genes had not been implicated in human aggression by previous studies, the most significantly enriched canonical pathways had been previously implicated in aggression (e.g., serotonin and dopamine signaling). Our findings provide strong evidence to support the causal role of these pathways in the pathogenesis of aggression. In addition, the novel genes and pathways we identified suggest additional mechanisms underlying the origins of human aggression. Genome-wide association studies with very large samples will be needed to determine if common variants in these genes are risk factors for aggression. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Biochemical toxicity and DNA damage of imidazolium-based ionic liquid with different anions in soil on Vicia faba seedlings.

PubMed

Liu, Tong; Zhu, Lusheng; Wang, Jinhua; Wang, Jun; Zhang, Jun; Sun, Xi; Zhang, Cheng

2015-12-17

In the present study, the toxic effects of 1-octyl-3-methylimidazolium chloride ([Omim]Cl), 1-octyl-3-methylimidazolium bromide ([Omim]Br) and 1-octyl-3-methylimidazolium tetrafluoroborate ([Omim]BF4) in soil on Vicia faba (V. faba) seedlings at 0, 100, 200, 400, 600 and 800 mg kg(-1) were assessed for the first time at the cellular and molecular level. Moreover, the toxicity of these three ionic liquids (ILs) was evaluated, and the influence of anions on the toxicity of the ILs was assessed. The results showed that even at 100 mg kg(-1), the growth of V. faba seedlings was inhibited after exposure to the three ILs, and the inhibitory effect was enhanced with increasing concentrations of the three ILs. The level of reactive oxygen species (ROS) was increased after exposure to the three ILs, which resulted in lipid peroxidation, DNA damage and oxidative damage in the cells of the V. faba seedlings. In addition, the anion structure could influence the toxicity of ILs, and toxicity of the three tested ILs decreased in the following order: [Omim]BF4 > [Omim]Br > [Omim]Cl. Moreover, oxidative damage is the primary mechanism by which ILs exert toxic effects on crops, and ILs could reduce the agricultural productivity.

PGMapper: a web-based tool linking phenotype to genes.

PubMed

Xiong, Qing; Qiu, Yuhui; Gu, Weikuan

2008-04-01

With the availability of whole genome sequence in many species, linkage analysis, positional cloning and microarray are gradually becoming powerful tools for investigating the links between phenotype and genotype or genes. However, in these methods, causative genes underlying a quantitative trait locus, or a disease, are usually located within a large genomic region or a large set of genes. Examining the function of every gene is very time consuming and needs to retrieve and integrate the information from multiple databases or genome resources. PGMapper is a software tool for automatically matching phenotype to genes from a defined genome region or a group of given genes by combining the mapping information from the Ensembl database and gene function information from the OMIM and PubMed databases. PGMapper is currently available for candidate gene search of human, mouse, rat, zebrafish and 12 other species. Available online at http://www.genediscovery.org/pgmapper/index.jsp.

Ectrodactyly with aplasia of long bones (OMIM; 119100) in a large inbred Arab family with an apparent autosomal dominant inheritance and reduced penetrance: clinical and genetic analysis.

PubMed

Naveed, Mohammed; Al-Ali, Mahmoud T; Murthy, Sabita K; Al-Hajali, Sarah; Al-Khaja, Najib; Deutsch, Samuel; Bottani, Armand; Antonarakis, Stylianos E; Nath, Swapan K; Radhakrishna, Uppala

2006-07-01

Ectrodactyly with aplasia of long bones syndrome is one of the most recognizable defects involving the extremities. We have studied a very large eight-generation consanguineous Arab family from the United Arab Emirates (UAE) with multiple severe limb anomalies resembling this condition (OMIM; 119100), for which the affected gene is unknown. The pedigree consists of 145 individuals including 23 affected (14 males/9 females) with limb anomalies. Of these, 18 had tibial aplasia (TA) usually on the right side. The expression of the phenotype was variable and ranged from bilateral to unilateral TA with ectrodactyly and other defects of the extremities. The mode of inheritance appears to be autosomal dominant with reduced penetrance. There were 10 consanguineous marriages observed in this pedigree. This could suggest possible pseudodominance due to high frequency of the mutant allele. Candidate loci for the described syndrome include GLI3 (OMIM: 165240) on 7p13, sonic hedgehog; (OMIM: 600725) on 7q36, Langer-Giedion syndrome (OMIM: 150230) on 8q24.1 and split-hand/foot malformation 3 (OMIM: 600095) on 10q24. In addition, bilateral tibial hemimelia and unilateral absence of the ulna was previously observed to co-segregate with deletion of 8q24.1. Two-point linkage and haplotype analyses did not show the involvement of the above regions in this family. (c) 2006 Wiley-Liss, Inc.

Patome: a database server for biological sequence annotation and analysis in issued patents and published patent applications.

PubMed

Lee, Byungwook; Kim, Taehyung; Kim, Seon-Kyu; Lee, Kwang H; Lee, Doheon

2007-01-01

With the advent of automated and high-throughput techniques, the number of patent applications containing biological sequences has been increasing rapidly. However, they have attracted relatively little attention compared to other sequence resources. We have built a database server called Patome, which contains biological sequence data disclosed in patents and published applications, as well as their analysis information. The analysis is divided into two steps. The first is an annotation step in which the disclosed sequences were annotated with RefSeq database. The second is an association step where the sequences were linked to Entrez Gene, OMIM and GO databases, and their results were saved as a gene-patent table. From the analysis, we found that 55% of human genes were associated with patenting. The gene-patent table can be used to identify whether a particular gene or disease is related to patenting. Patome is available at http://www.patome.org/; the information is updated bimonthly.

Patome: a database server for biological sequence annotation and analysis in issued patents and published patent applications

PubMed Central

Lee, Byungwook; Kim, Taehyung; Kim, Seon-Kyu; Lee, Kwang H.; Lee, Doheon

2007-01-01

With the advent of automated and high-throughput techniques, the number of patent applications containing biological sequences has been increasing rapidly. However, they have attracted relatively little attention compared to other sequence resources. We have built a database server called Patome, which contains biological sequence data disclosed in patents and published applications, as well as their analysis information. The analysis is divided into two steps. The first is an annotation step in which the disclosed sequences were annotated with RefSeq database. The second is an association step where the sequences were linked to Entrez Gene, OMIM and GO databases, and their results were saved as a gene–patent table. From the analysis, we found that 55% of human genes were associated with patenting. The gene–patent table can be used to identify whether a particular gene or disease is related to patenting. Patome is available at ; the information is updated bimonthly. PMID:17085479

SNPdbe: constructing an nsSNP functional impacts database.

PubMed

Schaefer, Christian; Meier, Alice; Rost, Burkhard; Bromberg, Yana

2012-02-15

Many existing databases annotate experimentally characterized single nucleotide polymorphisms (SNPs). Each non-synonymous SNP (nsSNP) changes one amino acid in the gene product (single amino acid substitution;SAAS). This change can either affect protein function or be neutral in that respect. Most polymorphisms lack experimental annotation of their functional impact. Here, we introduce SNPdbe-SNP database of effects, with predictions of computationally annotated functional impacts of SNPs. Database entries represent nsSNPs in dbSNP and 1000 Genomes collection, as well as variants from UniProt and PMD. SAASs come from >2600 organisms; 'human' being the most prevalent. The impact of each SAAS on protein function is predicted using the SNAP and SIFT algorithms and augmented with experimentally derived function/structure information and disease associations from PMD, OMIM and UniProt. SNPdbe is consistently updated and easily augmented with new sources of information. The database is available as an MySQL dump and via a web front end that allows searches with any combination of organism names, sequences and mutation IDs. http://www.rostlab.org/services/snpdbe.

Investigation of toxic effects of imidazolium ionic liquids, [bmim][BF4] and [omim][BF4], on marine mussel Mytilus galloprovincialis with or without the presence of conventional solvents, such as acetone.

PubMed

Tsarpali, Vasiliki; Belavgeni, Alexia; Dailianis, Stefanos

2015-07-01

This study investigated the cytotoxic, oxidative and genotoxic effects of two commonly used imidazolium ionic liquids (ILs), [bmim][BF4] (1-butyl-3-methylimidazolium) and [omim][BF4] (1-methyl-3-octylimidazolium tetrafluoroborate), on the marine mussel Mytilus galloprovincialis, as well as whether acetone could mediate their toxic profile. In this context, mussels were firstly exposed to different concentrations of [bmim][BF4] or [omim][BF4], with or without the presence of acetone (at a final concentration of 0.06% v/v), for a period of 96h, in order to determine the concentration that causes 50% mussel mortality (LC50 values) in each case. Thereafter, mussels were exposed to sub- and non-lethal concentrations of ILs for investigating their ability to cause lysosomal membrane impairment (with the use of neutral red retention assay/NRRT), superoxide anion and lipid peroxidation byproduct (malondialdehyde/MDA) formation, as well as DNA damage and formation of nuclear abnormalities in hemocytes. The results showed that [omim][BF4] was more toxic than [bmim][BF4] in all cases, while the presence of acetone resulted in a slight attenuation of its toxicity. The different toxic behavior of ILs was further revealed by the significantly lower levels of NRRT values observed in [omim][BF4]-treated mussels, compared to those occurring in [bmim][BF4] in all cases. Similarly, [bmim][BF4]-mediated oxidative and genotoxic effects were observed only in the highest concentration tested (10mgL(-1)), while [omim][BF4]-mediated effects were enhanced at lower concentrations (0.01-0.05mgL(-1)). Overall, the present study showed that [bmim][BF4] and [omim][BF4] could induce not only lethal but also nonlethal effects on mussel M. galloprovincialis. The extent of [bmim][BF4] and/or [omim][BF4]-mediated effects could be ascribed to the length of each IL alkyl chain, as well as to their lipophilicity. Moreover, the role of acetone on the obtained toxic effects of the specific ILs was reported for the first time, giving evidence for its interaction with the ILs and the modulation of their toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

How the spontaneous insertion of amphiphilic imidazolium-based cations changes biological membranes: a molecular simulation study.

PubMed

Lim, Geraldine S; Jaenicke, Stephan; Klähn, Marco

2015-11-21

The insertion of 1-octyl-3-methylimidazolium cations (OMIM(+)) from a diluted aqueous ionic liquid (IL) solution into a model of a bacterial cell membrane is investigated. Subsequently, the mutual interactions of cations inside the membrane and their combined effect on membrane properties are derived. The ionic liquid solution and the membrane model are simulated using molecular dynamics in combination with empirical force fields. A high propensity of OMIM(+) for membrane insertion is observed, with a cation concentration at equilibrium inside the membrane 47 times larger than in the solvent. Once inserted, cations exhibit a weak effective attraction inside the membrane at a distance of 1.3 nm. At this free energy minimum, negatively charged phosphates of the phospholipids are sandwiched between two OMIM(+) to form energetically favorable OMIM(+)-phosphate-OMIM(+) types of coordination. The cation-cation association free energy is 5.9 kJ mol(-1), whereas the activation barrier for dissociation is 10.1 kJ mol(-1). Subsequently, OMIM(+) are inserted into the leaflet of the membrane bilayer that represents the extracellular side. The cations are evenly distributed with mutual cation distances according to the found optimum distance of 1.3 nm. Because of the short length of the cation alkyl chains compared to lipid fatty acids, voids are generated in the hydrophobic core of the membrane. These voids disorder the fatty acids, because they enable fatty acids to curl into these empty spaces and also cause a thinning of the membrane by 0.6 nm. Additionally, the membrane density increases at its center. The presence of OMIM(+) in the membrane facilitates the permeation of small molecules such as ammonia through the membrane, which is chosen as a model case for small polar solutes. The permeability coefficient of the membrane with respect to ammonia increases substantially by a factor of seven. This increase is caused by a reduction of the involved free energy barriers, which is effected by the cations through the thinning of the membrane and favorable interactions of the delocalized OMIM(+) charge with ammonia inside the membrane. Overall, the results indicate the antimicrobial effect of amphiphilic imidazolium-based cations that are found in various common ILs. This effect is caused by an alteration of the permeability of the bacterial membrane and other property changes.

Molecular and comparative genetics of mental retardation.

PubMed Central

Inlow, Jennifer K; Restifo, Linda L

2004-01-01

Affecting 1-3% of the population, mental retardation (MR) poses significant challenges for clinicians and scientists. Understanding the biology of MR is complicated by the extraordinary heterogeneity of genetic MR disorders. Detailed analyses of >1000 Online Mendelian Inheritance in Man (OMIM) database entries and literature searches through September 2003 revealed 282 molecularly identified MR genes. We estimate that hundreds more MR genes remain to be identified. A novel test, in which we distributed unmapped MR disorders proportionately across the autosomes, failed to eliminate the well-known X-chromosome overrepresentation of MR genes and candidate genes. This evidence argues against ascertainment bias as the main cause of the skewed distribution. On the basis of a synthesis of clinical and laboratory data, we developed a biological functions classification scheme for MR genes. Metabolic pathways, signaling pathways, and transcription are the most common functions, but numerous other aspects of neuronal and glial biology are controlled by MR genes as well. Using protein sequence and domain-organization comparisons, we found a striking conservation of MR genes and genetic pathways across the approximately 700 million years that separate Homo sapiens and Drosophila melanogaster. Eighty-seven percent have one or more fruit fly homologs and 76% have at least one candidate functional ortholog. We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR. PMID:15020472

Microcephaly, microtia, preauricular tags, choanal atresia and developmental delay in three unrelated patients: a mandibulofacial dysostosis distinct from Treacher Collins syndrome.

PubMed

Wieczorek, Dagmar; Gener, Blanca; González, Ma Jesús Martínez; Seland, Saskia; Fischer, Sven; Hehr, Ute; Kuechler, Alma; Hoefsloot, Lies H; de Leeuw, Nicole; Gillessen-Kaesbach, Gabriele; Lohmann, Dietmar R

2009-05-01

Treacher Collins syndrome (TCS, OMIM 154500) is a well-defined mandibulofacial dysostosis characterized by symmetric facial anomalies consisting of malar hypoplasia, coloboma of the lower eyelid, dysplastic ears, micrognathia, cleft palate and deafness. Other mandibulofacial dysostoses (MDs) such as Toriello (OMIM 301950), Bauru (OMIM 604830), Hedera-Toriello-Petty (OMIM 608257), and Guion-Almeida (OMIM 610536) syndromes are less well characterized and much rarer. Here we describe three unrelated patients showing clinical features overlapping with TCS, but who in addition have developmental delay, microcephaly and a distinct facial gestalt. Because of the distinct ear anomalies and the hearing loss a HOXA2 mutation was taken into account. CHARGE syndrome was discussed because of ear anomalies, choanal atresia, and developmental delay in our patients. But mutational analyses including sequencing of the TCOF1, the HOXA2, and the CHD7 genes, deletion screening of the TCOF1 gene as well as genomewide array analyses revealed normal results. We suggest that these three patients have a new type of mandibulofacial dysostosis. As all three cases are sporadic and both sexes are affected the pattern of inheritance might be autosomal dominant or autosomal recessive. Identification of additional patients will allow to further delineate the phenotype, to assign the inheritance pattern and to identify the molecular basis.

The prevalence of chromosomal deletions relating to developmental delay and/or intellectual disability in human euploid blastocysts.

PubMed

He, Wenyin; Sun, Xiaofang; Liu, Lian; Li, Man; Jin, Hua; Wang, Wei-Hua

2014-01-01

Chromosomal anomalies in human embryos produced by in vitro fertilization are very common, which include numerical (aneuploidy) and structural (deletion, duplication or others) anomalies. Our previous study indicated that chromosomal deletion(s) is the most common structural anomaly accounting for approximately 8% of euploid blastocysts. It is still unknown if these deletions in human euploid blastocysts have clinical significance. In this study, we analyzed 15 previously diagnosed euploid blastocysts that had chromosomal deletion(s) using Agilent oligonucleotide DNA microarray platform and localized the gene location in each deletion. Then, we used OMIM gene map and phenotype database to investigate if these deletions are related with some important genes that cause genetic diseases, especially developmental delay or intellectual disability. As results, we found that the detectable chromosomal deletion size with Agilent microarray is above 2.38 Mb, while the deletions observed in human blastocysts are between 11.6 to 103 Mb. With OMIM gene map and phenotype database information, we found that deletions can result in loss of 81-464 genes. Out of these genes, 34-149 genes are related with known genetic problems. Furthermore, we found that 5 out of 15 samples lost genes in the deleted region, which were related to developmental delay and/or intellectual disability. In conclusion, our data indicates that all human euploid blastocysts with chromosomal deletion(s) are abnormal and transfer of these embryos may cause birth defects and/or developmental and intellectual disabilities. Therefore, the embryos with chromosomal deletion revealed by DNA microarray should not be transferred to the patients, or further gene map and/or phenotype seeking is necessary before making a final decision.

G6PDdb, an integrated database of glucose-6-phosphate dehydrogenase (G6PD) mutations.

PubMed

Kwok, Colin J; Martin, Andrew C R; Au, Shannon W N; Lam, Veronica M S

2002-03-01

G6PDdb (http://www.rubic.rdg.ac.uk/g6pd/ or http://www.bioinf.org.uk/g6pd/) is a newly created web-accessible locus-specific mutation database for the human Glucose-6-phosphate dehydrogenase (G6PD) gene. The relational database integrates up-to-date mutational and structural data from various databanks (GenBank, Protein Data Bank, etc.) with biochemically characterized variants and their associated phenotypes obtained from published literature and the Favism website. An automated analysis of the mutations likely to have a significant impact on the structure of the protein has been performed using a recently developed procedure. The database may be queried online and the full results of the analysis of the structural impact of mutations are available. The web page provides a form for submitting additional mutation data and is linked to resources such as the Favism website, OMIM, HGMD, HGVBASE, and the PDB. This database provides insights into the molecular aspects and clinical significance of G6PD deficiency for researchers and clinicians and the web page functions as a knowledge base relevant to the understanding of G6PD deficiency and its management. Copyright 2002 Wiley-Liss, Inc.

Raine Syndrome (OMIM #259775), Caused By FAM20C Mutation, Is Congenital Sclerosing Osteomalacia With Cerebral Calcification (OMIM 259660).

PubMed

Whyte, Michael P; McAlister, William H; Fallon, Michael D; Pierpont, Mary Ella; Bijanki, Vinieth N; Duan, Shenghui; Otaify, Ghada A; Sly, William S; Mumm, Steven

2017-04-01

In 1985, we briefly reported infant sisters with a unique, lethal, autosomal recessive disorder designated congenital sclerosing osteomalacia with cerebral calcification. In 1986, this condition was entered into Mendelian Inheritance In Man (MIM) as osteomalacia, sclerosing, with cerebral calcification (MIM 259660). However, no attestations followed. Instead, in 1989 Raine and colleagues published an affected neonate considering unprecedented the striking clinical and radiographic features. In 1992, "Raine syndrome" entered MIM formally as osteosclerotic bone dysplasia, lethal (MIM #259775). In 2007, the etiology emerged as loss-of-function mutation of FAM20C that encodes family with sequence similarity 20, member C. FAM20C is highly expressed in embryonic calcified tissues and encodes a kinase (dentin matrix protein 4) for most of the secreted phosphoproteome including FGF23, osteopontin, and other regulators of skeletal mineralization. Herein, we detail the clinical, radiological, biochemical, histopathological, and FAM20C findings of our patients. Following premortem tetracycline labeling, the proposita's non-decalcified skeletal histopathology after autopsy indicated no rickets but documented severe osteomalacia. Archival DNA revealed the sisters were compound heterozygotes for a unique missense mutation and a novel deletion in FAM20C. Individuals heterozygous for the missense mutation seemed to prematurely fuse their metopic suture and develop a metopic ridge sometimes including trigonocephaly. Our findings clarify FAM20C's role in hard tissue formation and mineralization, and show that Raine syndrome is congenital sclerosing osteomalacia with cerebral calcification. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Toxic effects of ionic liquid 1-octyl-3-methylimidazolium tetrafluoroborate on soil enzyme activity and soil microbial community diversity.

PubMed

Sun, Xi; Zhu, Lusheng; Wang, Jinhua; Wang, Jun; Su, Benying; Liu, Tong; Zhang, Cheng; Gao, Chong; Shao, Yuting

2017-01-01

Ionic liquids (ILs) were considered as "green" solvents and have been used widely because of their excellent properties. But ILs are not as "green" as has been suggested, and the toxic effects of ILs on organisms have been shown in recent years. In the present study, the toxic effects of the IL 1-octyl-3-methylimidazolium tetrafluoroborate ([Omim]BF 4 ) on soil enzyme activity and soil microbial communities at three different concentrations (1.0, 5.0 and 10.0mg/kg) and a control treatment over 40 days of incubation time (sampled on days 10, 20, 30 and 40) were examined under laboratory conditions. The concentrations of [Omim]BF 4 in soils were detected by high performance liquid chromatography (HPLC) and the results indicated that [Omim]BF 4 were maintained stable in the soil during the exposure period. However, the enzyme activity results showed that urease activity was stimulated on day 20 and then decreased after 30 days of incubation. The activity of β-glucosidase was stimulated after 20 days of incubation in both treatment groups. Moreover, both dehydrogenase and acid phosphatase were inhibited at a high level (10.0mg/kg) only on day 20. The analysis of terminal restriction fragment length polymorphism (T-RFLP) revealed that the soil microbial community structures were altered by [Omim]BF 4 and that the soil microbial diversity and evenness of high levels (5.0mg/kg and 10.0mg/kg) treatments were decreased. Moreover, the dominant structure of the microbial communities was not changed by [Omim]BF 4 . Furthermore, the abundance of the ammonia monooxygenase (amoA) genes of both ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) was examined using real time polymerase chain reaction (RT-PCR). The results revealed that the copy numbers of the amoA-gene were decreased by [Omim]BF 4 with the 5.0 and 10.0mg/kg treatments. Based on the experiment, we concluded that high levels (5.0 and 10.0mg/kg) of [Omim]BF 4 could have significantly toxic effects on soil enzyme activities and the diversity of the microbial communities. Copyright © 2016 Elsevier Inc. All rights reserved.

An ensemble rank learning approach for gene prioritization.

PubMed

Lee, Po-Feng; Soo, Von-Wun

2013-01-01

Several different computational approaches have been developed to solve the gene prioritization problem. We intend to use the ensemble boosting learning techniques to combine variant computational approaches for gene prioritization in order to improve the overall performance. In particular we add a heuristic weighting function to the Rankboost algorithm according to: 1) the absolute ranks generated by the adopted methods for a certain gene, and 2) the ranking relationship between all gene-pairs from each prioritization result. We select 13 known prostate cancer genes in OMIM database as training set and protein coding gene data in HGNC database as test set. We adopt the leave-one-out strategy for the ensemble rank boosting learning. The experimental results show that our ensemble learning approach outperforms the four gene-prioritization methods in ToppGene suite in the ranking results of the 13 known genes in terms of mean average precision, ROC and AUC measures.

Graphical user interfaces for symbol-oriented database visualization and interaction

NASA Astrophysics Data System (ADS)

Brinkschulte, Uwe; Siormanolakis, Marios; Vogelsang, Holger

1997-04-01

In this approach, two basic services designed for the engineering of computer based systems are combined: a symbol-oriented man-machine-service and a high speed database-service. The man-machine service is used to build graphical user interfaces (GUIs) for the database service; these interfaces are stored using the database service. The idea is to create a GUI-builder and a GUI-manager for the database service based upon the man-machine service using the concept of symbols. With user-definable and predefined symbols, database contents can be visualized and manipulated in a very flexible and intuitive way. Using the GUI-builder and GUI-manager, a user can build and operate its own graphical user interface for a given database according to its needs without writing a single line of code.

Report of a Novel SHOX Missense Variant in a Boy With Short Stature and His Mother With Leri–Weill Dyschondrosteosis

PubMed Central

Lucchetti, Laura; Prontera, Paolo; Mencarelli, Amedea; Sallicandro, Ester; Mencarelli, Annalisa; Cofini, Marta; Leonardi, Alberto; Stangoni, Gabriela; Penta, Laura; Esposito, Susanna

2018-01-01

Heterozygous mutations in the SHOX gene or in the upstream and downstream enhancer elements are associated with 2–22% of cases of idiopathic short stature (OMIM #300582) and with 60% of cases of Leri–Weill dyschondrosteosis (OMIM #127300) with which female subjects are generally more severely affected. Approximately 80–90% of SHOX pathogenic variants are deletions or duplications, and the remaining 10–20% are point mutations that primarily give rise to missense variants. The clinical interpretation of novel variants, particularly missense variants, can be challenging and can remain of uncertain significance. Here, we describe a novel missense variant (c.1044 G>T, p.Arg118Met) in a Moroccan boy with a disproportionately short stature and without any radiological traits or bone deformities and in his mother, who had a disproportionately short stature and a Madelung deformity. This variant has not been reported to date in the updated SHOX allelic variant or Human Gene Mutation Databases nor is it listed as a polymorphism in the ExAC browser, dbSNP, or 1000G. This mutation was predicted to be deleterious by three different bioinformatics tools since it modifies an amino acid in a highly conserved DNA-binding domain of the SHOX protein. Based on this evidence, the patient was treated with recombinant human growth hormone. PMID:29692759

Mapping PDB chains to UniProtKB entries.

PubMed

Martin, Andrew C R

2005-12-01

UniProtKB/SwissProt is the main resource for detailed annotations of protein sequences. This database provides a jumping-off point to many other resources through the links it provides. Among others, these include other primary databases, secondary databases, the Gene Ontology and OMIM. While a large number of links are provided to Protein Data Bank (PDB) files, obtaining a regularly updated mapping between UniProtKB entries and PDB entries at the chain or residue level is not straightforward. In particular, there is no regularly updated resource which allows a UniProtKB/SwissProt entry to be identified for a given residue of a PDB file. We have created a completely automatically maintained database which maps PDB residues to residues in UniProtKB/SwissProt and UniProtKB/trEMBL entries. The protocol uses links from PDB to UniProtKB, from UniProtKB to PDB and a brute-force sequence scan to resolve PDB chains for which no annotated link is available. Finally the sequences from PDB and UniProtKB are aligned to obtain a residue-level mapping. The resource may be queried interactively or downloaded from http://www.bioinf.org.uk/pdbsws/.

Acquired perforating dermatosis in a patient with Poland syndrome.

PubMed

Fistarol, Susanna K; Itin, Peter H

2003-01-01

Acquired perforating dermatosis (APD) is characterized by umbilicated 1- to 10-mm-measuring papulonodules with a central adherent oystershell-like keratotic plug, typically on the dorsa of the hands, forearms and over the knees. APD is associated with systemic diseases, especially diabetes mellitus and/or renal failure. Histologically the lesions show transepidermal elimination of altered dermal components into a cup-shaped epidermal depression. We present a 69-year-old man with coexisting APD and Poland syndrome (PS), an association not yet described. PS (OMIM 173800) is a rare congenital anomaly consisting of unilateral partial or total absence of the greater pectoralis muscle and ipsilateral symbrachydactyly. Most cases of PS are sporadic as it was in our case. Our patient had, in addition, an untreated diabetic condition, hyperuricaemia, dilated cardiomyopathy and a very recent pulmonary embolism. He responded to therapy with allopurinol. Copyright 2003 S. Karger AG, Basel

PhenoVar: a phenotype-driven approach in clinical genomics for the diagnosis of polymalformative syndromes

PubMed Central

2014-01-01

Background We propose a phenotype-driven analysis of encrypted exome data to facilitate the widespread implementation of exome sequencing as a clinical genetic screening test. Twenty test-patients with varied syndromes were selected from the literature. For each patient, the mutation, phenotypic data, and genetic diagnosis were available. Next, control exome-files, each modified to include one of these twenty mutations, were assigned to the corresponding test-patients. These data were used by a geneticist blinded to the diagnoses to test the efficiency of our software, PhenoVar. The score assigned by PhenoVar to any genetic diagnosis listed in OMIM (Online Mendelian Inheritance in Man) took into consideration both the patient’s phenotype and all variations present in the corresponding exome. The physician did not have access to the individual mutations. PhenoVar filtered the search using a cut-off phenotypic match threshold to prevent undesired discovery of incidental findings and ranked the OMIM entries according to diagnostic score. Results When assigning the same weight to all variants in the exome, PhenoVar predicted the correct diagnosis in 10/20 patients, while in 15/20 the correct diagnosis was among the 4 highest ranked diagnoses. When assigning a higher weight to variants known, or bioinformatically predicted, to cause disease, PhenoVar’s yield increased to 14/20 (18/20 in top 4). No incidental findings were identified using our cut-off phenotypic threshold. Conclusion The phenotype-driven approach described could render widespread use of ES more practical, ethical and clinically useful. The implications about novel disease identification, advancement of complex diseases and personalized medicine are discussed. PMID:24884844

Novel mutations of the SRD5A2 and AR genes in Thai patients with 46, XY disorders of sex development.

PubMed

Ittiwut, Chupong; Pratuangdejkul, Jaturong; Supornsilchai, Vichit; Muensri, Sasipa; Hiranras, Yodporn; Sahakitrungruang, Taninee; Watcharasindhu, Suttipong; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

2017-01-01

Abnormalities of dihydrotestosterone conversion [5α-reductase deficiency: online Mendelian inheritance in man (OMIM) 607306] or actions of androgens [partial androgen insensitivity syndrome (PAIS): OMIM 312300] during the 8th-12th weeks of gestation cause varying degrees of undervirilized external genitalia in 46, XY disorders of sex development (DSD) with increased testosterone production. The objective of the study was to determine clinical and genetic characteristics of Thai patients with 46, XY DSD. A cross-sectional study was conducted in 46, XY DSD with increased testosterone production (n=43) evaluated by a human chorionic gonadotropin (hCG) stimulation test or clinical features consistent with 5α-reductase deficiency or PAIS. PCR sequencing of the entire coding regions of the SRD5A2 and AR genes was performed. Molecular modeling analysis of the androgen receptor-ligand-binding domain (AR-LBD) of a novel mutation was constructed. Mutations were found in seven patients (16.3%): five (11.6%) and two (4.7%) patients had mutations in SRD5A2 and AR, respectively. Two novel mutations, SRD5A2 c.383A>G (p.Y128C) and AR c.2176C>T (p.R726C), were identified. Dimensional structural analysis of the novel mutated AR (p.R726C) revealed that it affected the co-activator binding [binding function-3 (BF-3)], not the testosterone binding site. Short phallus length was associated with 5α-reductase deficiency. Around 16.3% of our patients with 46, XY DSD had 5α-reductase deficiency or PAIS. Two novel mutations of SRD5A2 and AR were identified. The novel mutated AR (p.R726C) might affect the co-activator binding (BF-3), not the testosterone binding site.

The morbid anatomy of the human genome: chromosomal location of mutations causing disease.

PubMed Central

McKusick, V A; Amberger, J S

1993-01-01

Information is given in tabular form derived from a synopsis of the human gene map which has been updated continuously since 1973 as part of Mendelian Inheritance in Man (Johns Hopkins University Press, 10th ed, 1992) and of OMIM (Online Mendelian Inheritance in Man, available generally since 1987). The part of the synopsis reproduced here consists of chromosome by chromosome gene lists of loci for which there are associated disorders (table 1), a pictorial representation of this information (fig 1a-d), and an index of disorders for which the causative mutations have been mapped (table 2). In table 1, information on genes that have been located to specific chromosomal positions and are also the site of disease producing mutations is arranged by chromosome, starting with chromosome 1 and with the end of the short arm of the chromosome in each case. In table 2 an alphabetized list of these disorders and the chromosomal location of the mutation in each case are provided. Both in the 'Disorder' field of table 1 and in table 2, the numbers 1, 2, or 3 in parentheses after the name of the disorder indicate that its chromosomal location was determined by mapping of the wildtype gene (1), by mapping of the clinical phenotype (2), or by both strategies (3). PMID:8423603

Toxicity of two imidazolium ionic liquids, [bmim][BF4] and [omim][BF4], to standard aquatic test organisms: Role of acetone in the induced toxicity.

PubMed

Tsarpali, Vasiliki; Dailianis, Stefanos

2015-07-01

The main goal of this study was to investigate the toxicity of the imidazolium-based ionic liquids (ILs), [bmim][BF4] (1-butyl-3-methylimidazolium tetrafluoroborate) and [omim][BF4] (1-octyl-3-methylimidazolium tetrafluoroborate), in battery of standard aquatic toxicity test organisms. Specifically, exposure of the algae Scenedesmus rubescens, crustaceans Thamnocephalus platyurus and Artemia franciscana, rotifers Brachionus calyciflorus and Brachionus plicatilis and bivalve Mytilus galloprovincialis to different concentrations of [bmim][BF4], [omim][BF4] and/or a binary mixture of [bmim][BF4]-[omim][BF4] (1:1) with or without acetone (carrier solvent), revealed that solvent can differentially mediate ILs' toxic profile. Acetone's ability to differentially affect ILs' cation's alkyl chain length, as well as the hydrolysis of [BF4(-)] anions was evident. Given that the toxic potency of the tested ILs seemed to be equal or even higher (in some cases) than those of conventional organic solvents, the present study revealed that the characterization of imidazolium-based ILs as "green solvents" should not be generalized, at least in case of their natural occurrence in mixtures with organic solvents, such as acetone. Copyright © 2015 Elsevier Inc. All rights reserved.

ImmunemiR - A Database of Prioritized Immune miRNA Disease Associations and its Interactome.

PubMed

Prabahar, Archana; Natarajan, Jeyakumar

2017-01-01

MicroRNAs are the key regulators of gene expression and their abnormal expression in the immune system may be associated with several human diseases such as inflammation, cancer and autoimmune diseases. Elucidation of miRNA disease association through the interactome will deepen the understanding of its disease mechanisms. A specialized database for immune miRNAs is highly desirable to demonstrate the immune miRNA disease associations in the interactome. miRNAs specific to immune related diseases were retrieved from curated databases such as HMDD, miR2disease and PubMed literature based on MeSH classification of immune system diseases. The additional data such as miRNA target genes, genes coding protein-protein interaction information were compiled from related resources. Further, miRNAs were prioritized to specific immune diseases using random walk ranking algorithm. In total 245 immune miRNAs associated with 92 OMIM disease categories were identified from external databases. The resultant data were compiled as ImmunemiR, a database of prioritized immune miRNA disease associations. This database provides both text based annotation information and network visualization of its interactome. To our knowledge, ImmunemiR is the first available database to provide a comprehensive repository of human immune disease associated miRNAs with network visualization options of its target genes, protein-protein interactions (PPI) and its disease associations. It is freely available at http://www.biominingbu.org/immunemir/. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Remodeling Cildb, a popular database for cilia and links for ciliopathies

PubMed Central

2014-01-01

Background New generation technologies in cell and molecular biology generate large amounts of data hard to exploit for individual proteins. This is particularly true for ciliary and centrosomal research. Cildb is a multi–species knowledgebase gathering high throughput studies, which allows advanced searches to identify proteins involved in centrosome, basal body or cilia biogenesis, composition and function. Combined to localization of genetic diseases on human chromosomes given by OMIM links, candidate ciliopathy proteins can be compiled through Cildb searches. Methods Othology between recent versions of the whole proteomes was computed using Inparanoid and ciliary high throughput studies were remapped on these recent versions. Results Due to constant evolution of the ciliary and centrosomal field, Cildb has been recently upgraded twice, with new species whole proteomes and new ciliary studies, and the latter version displays a novel BioMart interface, much more intuitive than the previous ones. Conclusions This already popular database is designed now for easier use and is up to date in regard to high throughput ciliary studies. PMID:25422781

Microcephaly: general considerations and aids to nosology.

PubMed

Opitz, J M; Holt, M C

1990-01-01

Microcephaly is defined as an occipito-frontal head circumference (OFC) 2 or more standard deviations below the mean for age and sex using the new Roche et al. [Pediatrics 1987;79:706-712] charts, and corrected for parental OFC by the method of Weaver and Christian [J Pediatr 1980;96:990-994]. "Relative" microcephaly, i.e., a small head on a small child, may be associated with a much better intellectual prognosis than absolute microcephaly, although the average IQ of children with absolute microcephaly ascertained in a normal school system is normal when compared with that of appropriate control children. "Primary" microcephaly means an abnormal OFC at birth (corrected for gestational age and length), and "secondary" microcephaly a normal birth OFC with later, acquired microcephaly due to deceleration of brain growth reflecting infection, trauma, intoxication, metabolic disease, the Rett syndrome, or a true CNS degenerative disease. Some cases of syndromal microcephaly may be associated with normal intelligence including some "primordial dwarfs," children with Dubowitz syndrome, FAS, mild SC-Roberts syndrome, and an occasional Brachmann-de Lange individual. The nosology of (syndromal) microcephaly is extraordinarily complex and requires the assistance of special library resources and information retrieval expertise. At a minimum, it requires McKusick's Catalog of Mendelian Inheritance in Man (MIM); however, we find that our work is greatly enhanced by recently developed electronic databases such as MIM-online (OMIM), POSSUM, SYNDROME, and MEDLINE, as well. Three groups of syndromal and non-syndromal microcephaly are discussed selectively in order to illustrate the marvels of pleiotropy in human development and its abnormalities and the difficulties encountered in splitting and lumping entities with overlapping manifestations.

Comprehensive coverage of cardiovascular disease data in the disease portals at the Rat Genome Database.

PubMed

Wang, Shur-Jen; Laulederkind, Stanley J F; Hayman, G Thomas; Petri, Victoria; Smith, Jennifer R; Tutaj, Marek; Nigam, Rajni; Dwinell, Melinda R; Shimoyama, Mary

2016-08-01

Cardiovascular diseases are complex diseases caused by a combination of genetic and environmental factors. To facilitate progress in complex disease research, the Rat Genome Database (RGD) provides the community with a disease portal where genome objects and biological data related to cardiovascular diseases are systematically organized. The purpose of this study is to present biocuration at RGD, including disease, genetic, and pathway data. The RGD curation team uses controlled vocabularies/ontologies to organize data curated from the published literature or imported from disease and pathway databases. These organized annotations are associated with genes, strains, and quantitative trait loci (QTLs), thus linking functional annotations to genome objects. Screen shots from the web pages are used to demonstrate the organization of annotations at RGD. The human cardiovascular disease genes identified by annotations were grouped according to data sources and their annotation profiles were compared by in-house tools and other enrichment tools available to the public. The analysis results show that the imported cardiovascular disease genes from ClinVar and OMIM are functionally different from the RGD manually curated genes in terms of pathway and Gene Ontology annotations. The inclusion of disease genes from other databases enriches the collection of disease genes not only in quantity but also in quality. Copyright © 2016 the American Physiological Society.

ChiTaRS-3.1-the enhanced chimeric transcripts and RNA-seq database matched with protein-protein interactions.

PubMed

Gorohovski, Alessandro; Tagore, Somnath; Palande, Vikrant; Malka, Assaf; Raviv-Shay, Dorith; Frenkel-Morgenstern, Milana

2017-01-04

Discovery of chimeric RNAs, which are produced by chromosomal translocations as well as the joining of exons from different genes by trans-splicing, has added a new level of complexity to our study and understanding of the transcriptome. The enhanced ChiTaRS-3.1 database (http://chitars.md.biu.ac.il) is designed to make widely accessible a wealth of mined data on chimeric RNAs, with easy-to-use analytical tools built-in. The database comprises 34 922: chimeric transcripts along with 11 714: cancer breakpoints. In this latest version, we have included multiple cross-references to GeneCards, iHop, PubMed, NCBI, Ensembl, OMIM, RefSeq and the Mitelman collection for every entry in the 'Full Collection'. In addition, for every chimera, we have added a predicted Chimeric Protein-Protein Interaction (ChiPPI) network, which allows for easy visualization of protein partners of both parental and fusion proteins for all human chimeras. The database contains a comprehensive annotation for 34 922: chimeric transcripts from eight organisms, and includes the manual annotation of 200 sense-antiSense (SaS) chimeras. The current improvements in the content and functionality to the ChiTaRS database make it a central resource for the study of chimeric transcripts and fusion proteins. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Twenty years of audiology in a patient with Norrie disease.

PubMed

Halpin, Chris; Sims, Katherine

2008-11-01

To describe disease progression and treatment outcomes over a 20-year period (ages 5-25) in a young man with Norrie disease (occuloacousticocerebral dysplasia), ND; OMIM #310600. Affected individuals are born blind and develop progressive sensory loss with onset in adolescence. This disease is X-linked and has been associated with mutations of the NDP gene (Xp11.4). The patient was followed using repeated audiograms, as well as reports of educational progress and hearing aid use. The specific mutation was found by molecular analysis. The patient demonstrated progressive sensory loss with good preservation of word recognition. The loss was initially high frequency and asymmetric in adolescence and became more severe, more symmetric and affected practically all frequencies by the end of childhood. Educational progress was affected by the cognitive effects of the syndrome, and hearing aid use was very effective. A bilateral progressive sensory loss with good preservation of word recognition was documented in detail. The residual word recognition supported good use of hearing aids in this case.

amamutdb.no: A relational database for MAN2B1 allelic variants that compiles genotypes, clinical phenotypes, and biochemical and structural data of mutant MAN2B1 in α-mannosidosis.

PubMed

Riise Stensland, Hilde Monica Frostad; Frantzen, Gabrio; Kuokkanen, Elina; Buvang, Elisabeth Kjeldsen; Klenow, Helle Bagterp; Heikinheimo, Pirkko; Malm, Dag; Nilssen, Øivind

2015-06-01

α-Mannosidosis is an autosomal recessive lysosomal storage disorder caused by mutations in the MAN2B1 gene, encoding lysosomal α-mannosidase. The disorder is characterized by a range of clinical phenotypes of which the major manifestations are mental impairment, hearing impairment, skeletal changes, and immunodeficiency. Here, we report an α-mannosidosis mutation database, amamutdb.no, which has been constructed as a publicly accessible online resource for recording and analyzing MAN2B1 variants (http://amamutdb.no). Our aim has been to offer structured and relational information on MAN2B1 mutations and genotypes along with associated clinical phenotypes. Classifying missense mutations, as pathogenic or benign, is a challenge. Therefore, they have been given special attention as we have compiled all available data that relate to their biochemical, functional, and structural properties. The α-mannosidosis mutation database is comprehensive and relational in the sense that information can be retrieved and compiled across datasets; hence, it will facilitate diagnostics and increase our understanding of the clinical and molecular aspects of α-mannosidosis. We believe that the amamutdb.no structure and architecture will be applicable for the development of databases for any monogenic disorder. © 2015 WILEY PERIODICALS, INC.

HAEdb: a novel interactive, locus-specific mutation database for the C1 inhibitor gene.

PubMed

Kalmár, Lajos; Hegedüs, Tamás; Farkas, Henriette; Nagy, Melinda; Tordai, Attila

2005-01-01

Hereditary angioneurotic edema (HAE) is an autosomal dominant disorder characterized by episodic local subcutaneous and submucosal edema and is caused by the deficiency of the activated C1 esterase inhibitor protein (C1-INH or C1INH; approved gene symbol SERPING1). Published C1-INH mutations are represented in large universal databases (e.g., OMIM, HGMD), but these databases update their data rather infrequently, they are not interactive, and they do not allow searches according to different criteria. The HAEdb, a C1-INH gene mutation database (http://hae.biomembrane.hu) was created to contribute to the following expectations: 1) help the comprehensive collection of information on genetic alterations of the C1-INH gene; 2) create a database in which data can be searched and compared according to several flexible criteria; and 3) provide additional help in new mutation identification. The website uses MySQL, an open-source, multithreaded, relational database management system. The user-friendly graphical interface was written in the PHP web programming language. The website consists of two main parts, the freely browsable search function, and the password-protected data deposition function. Mutations of the C1-INH gene are divided in two parts: gross mutations involving DNA fragments >1 kb, and micro mutations encompassing all non-gross mutations. Several attributes (e.g., affected exon, molecular consequence, family history) are collected for each mutation in a standardized form. This database may facilitate future comprehensive analyses of C1-INH mutations and also provide regular help for molecular diagnostic testing of HAE patients in different centers.

The role of the cilium in hereditary tumor predisposition syndromes

PubMed Central

Klasson, Timothy D.; Giles, Rachel H.

2014-01-01

The primary cilium is a highly conserved cell organelle that is closely connected to processes involved in cell patterning and replication. Amongst their many functions, cilia act as “signal towers” through which cell-cell signaling cascades pass. Dysfunction of cilia or the myriad processes that are connected with cilium function can lead to disease. Due to the sheer number of cellular processes that at some point involve the primary cilium, the effects of misregulation are highly heterogeneous between different cell populations. However, because of the importance of primary cilia in the development, growth, patterning and orientation of cells and tissues, a common thread has emerged in which defective cilia can lead to disorganization, which can contribute to the growth of neoplasms, including cancer and pre-cancerous phenotypes. Because cilia are so vital for signaling during cell replication and the cell fate decisions that are important in childhood growth, symptoms often arise early in life. Here we review recent work connecting misregulation of the primary cilium with tumor formation in a variety of tissues in the developing body, with a particular focus on the syndromes in which classic tumor genes are mutated, including von Hippel-Lindau disease (OMIM 193300), adenomatous polyposis coli (OMIM 175100), tuberous sclerosis (OMIM 191100) and Birt-Hogg-Dubé syndrome (OMIM 135150). Timely diagnosis of these syndromes is essential for entry into appropriate screening protocols, which have been shown to effectively prolong life expectancy in these cohorts of patients. PMID:27625869

A possible cranio-oro-facial phenotype in Cockayne syndrome

PubMed Central

2013-01-01

Background Cockayne Syndrome CS (Type A – CSA; or CS Type I OMIM #216400) (Type B – CSB; or CS Type II OMIM #133540) is a rare autosomal recessive neurological disease caused by defects in DNA repair characterized by progressive cachectic dwarfism, progressive intellectual disability with cerebral leukodystrophy, microcephaly, progressive pigmentary retinopathy, sensorineural deafness photosensitivity and possibly orofacial and dental anomalies. Methods We studied the cranio-oro-facial status of a group of 17 CS patients from 15 families participating in the National Hospital Program for Clinical Research (PHRC) 2005 « Clinical and molecular study of Cockayne syndrome ». All patients were examined by two investigators using the Diagnosing Dental Defects Database (D[4]/phenodent) record form. Results Various oro-facial and dental anomalies were found: retrognathia; micrognathia; high- arched narrow palate; tooth crowding; hypodontia (missing permanent lateral incisor, second premolars or molars), screwdriver shaped incisors, microdontia, radiculomegaly, and enamel hypoplasia. Eruption was usually normal. Dental caries was associated with enamel defects, a high sugar/carbohydrate soft food diet, poor oral hygiene and dry mouth. Cephalometric analysis revealed mid-face hypoplasia, a small retroposed mandible and hypo-development of the skull. Conclusion CS patients may have associated oro-dental features, some of which may be more frequent in CS children – some of them being described for the first time in this paper (agenesis of second permanent molars and radiculomegaly). The high susceptibility to rampant caries is related to a combination of factors as well as enamel developmental defects. Specific attention to these anomalies may contribute to diagnosis and help plan management. PMID:23311583

DR-GAS: a database of functional genetic variants and their phosphorylation states in human DNA repair systems.

PubMed

Sehgal, Manika; Singh, Tiratha Raj

2014-04-01

We present DR-GAS(1), a unique, consolidated and comprehensive DNA repair genetic association studies database of human DNA repair system. It presents information on repair genes, assorted mechanisms of DNA repair, linkage disequilibrium, haplotype blocks, nsSNPs, phosphorylation sites, associated diseases, and pathways involved in repair systems. DNA repair is an intricate process which plays an essential role in maintaining the integrity of the genome by eradicating the damaging effect of internal and external changes in the genome. Hence, it is crucial to extensively understand the intact process of DNA repair, genes involved, non-synonymous SNPs which perhaps affect the function, phosphorylated residues and other related genetic parameters. All the corresponding entries for DNA repair genes, such as proteins, OMIM IDs, literature references and pathways are cross-referenced to their respective primary databases. DNA repair genes and their associated parameters are either represented in tabular or in graphical form through images elucidated by computational and statistical analyses. It is believed that the database will assist molecular biologists, biotechnologists, therapeutic developers and other scientific community to encounter biologically meaningful information, and meticulous contribution of genetic level information towards treacherous diseases in human DNA repair systems. DR-GAS is freely available for academic and research purposes at: http://www.bioinfoindia.org/drgas. Copyright © 2014 Elsevier B.V. All rights reserved.

Deep desulfurization by amphiphilic lanthanide-containing polyoxometalates in ionic-liquid emulsion systems under mild conditions.

PubMed

Xu, Junhua; Zhao, Shen; Ji, Yuanchun; Song, Yu-Fei

2013-01-07

Amphiphilic lanthanide-containing polyoxometalates (POMs) were prepared by surfactant encapsulation. Investigation of these lanthanide-containing POMs in oxidative desulfurization (ODS) showed that highly efficient deep desulfurization could be achieved in only 14 min with 100% conversion of dibenzothiophene under mild conditions by using (DDA)(9)LaW(10)/[omim]PF(6) (DDA=dimethyldioctadecylammonium, omim=1-octyl-3-methyl-imidazolium) in the presence of H(2) O(2) . Furthermore, deep desulfurization proceeds smoothly in model oil with an S content as low as 50 ppm. A scaled-up experiment in which the volume of model oil was increased from 5 to 1000 mL with S content of 1000 ppm indicated that about 99% sulfur removal can be achieved in 40 mins in an ionic-liquid emulsion system. To the best of our knowledge, the (DDA)(9)LaW(10)/[omim]PF(6) catalyst system with H(2)O(2) as oxidant is one of the most efficient desulfurization systems reported so far. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

PubMed Central

Köhler, Sebastian; Doelken, Sandra C.; Mungall, Christopher J.; Bauer, Sebastian; Firth, Helen V.; Bailleul-Forestier, Isabelle; Black, Graeme C. M.; Brown, Danielle L.; Brudno, Michael; Campbell, Jennifer; FitzPatrick, David R.; Eppig, Janan T.; Jackson, Andrew P.; Freson, Kathleen; Girdea, Marta; Helbig, Ingo; Hurst, Jane A.; Jähn, Johanna; Jackson, Laird G.; Kelly, Anne M.; Ledbetter, David H.; Mansour, Sahar; Martin, Christa L.; Moss, Celia; Mumford, Andrew; Ouwehand, Willem H.; Park, Soo-Mi; Riggs, Erin Rooney; Scott, Richard H.; Sisodiya, Sanjay; Vooren, Steven Van; Wapner, Ronald J.; Wilkie, Andrew O. M.; Wright, Caroline F.; Vulto-van Silfhout, Anneke T.; de Leeuw, Nicole; de Vries, Bert B. A.; Washingthon, Nicole L.; Smith, Cynthia L.; Westerfield, Monte; Schofield, Paul; Ruef, Barbara J.; Gkoutos, Georgios V.; Haendel, Melissa; Smedley, Damian; Lewis, Suzanna E.; Robinson, Peter N.

2014-01-01

The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online. PMID:24217912

Assured crew return vehicle man-systems integration standards

NASA Technical Reports Server (NTRS)

1991-01-01

This is Volume 6 of the Man-Systems Integration Standards (MSIS) family of documents, which is contained in several volumes and a relational database. Each volume has a specific purpose, and each has been assembled from the data contained in the relational database. Volume 6 serves as the Assured Crew Return Vehicle project man-systems integration design requirements. The data in this document is a subset of the data found in Volume 1 and defines the requirements which are pertinent to the Assured Crew Return Vehicle as defined in the SPRD. Additional data and guidelines are provided to assist in the design.

Fecundity in an infertile man with r(15) - a challenge to the current paradigm.

PubMed

Kalantari, Hamid; Karimi, Hamideh; Almadani, Seyed Navid; Fakhri, Mostafa; Mokhtari, Pegah; Gourabi, Hamid; Mohseni Meybodi, Anahita

2018-02-01

Ring chromosome 15 [r(15)] is a rare condition with a mild-to-severe growth failure, mental disabilities, café-au-lait spots, specific facial features, fertility difficulties and other minor dysmorphic stigmata. Of almost 50 affected individuals reported in the literature, none were assessed for the precise breakpoint positioning, which creates uncertainty in defining a specific phenotype for the deleted segment. This study reports for the first time the vertical transmission of r(15) in three consecutive generations of a family, including a subfertile man, his mother and his newborn infant. Array comparative genomic hybridization results revealed a 563 kb deletion of 15q26.3, overlapping the OMIM genes SNRP1, PCSK6 and TM2D3. The hemizygosity was confirmed with real-time quantitative PCR. Regarding haploinsufficiency in 15q26.3, based on phenotypic characteristics of the carriers, the only rational conclusion is that SNRPA1, PCSK6 and TM2D3 are not gene-dosage sensitive and are probably inherited in an autosomal-recessive manner. Given growth deficiency in r(15) carriers, this shows that the growth retardation cannot be attributed entirely to IGF1R. The predominance of female patients with r(15) is the next as yet unanswered question; incomplete penetrance and/or variable expression of gene(s) in different genders may be involved, but further evidence is needed to support this idea. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Autosomal-dominant nystagmus, foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation.

PubMed

Thomas, Shery; Thomas, Mervyn G; Andrews, Caroline; Chan, Wai-Man; Proudlock, Frank A; McLean, Rebecca J; Pradeep, Archana; Engle, Elizabeth C; Gottlob, Irene

2014-03-01

Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C>G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The amino-acid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation.

Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant.

PubMed

Pomerantz, Daniel J; Ferdinandusse, Sacha; Cogan, Joy; Cooper, David N; Reimschisel, Tyler; Robertson, Amy; Bican, Anna; McGregor, Tracy; Gauthier, Jackie; Millington, David S; Andrae, Jaime L W; Tschannen, Michael R; Helbling, Daniel C; Demos, Wendy M; Denis, Simone; Wanders, Ronald J A; Newman, John N; Hamid, Rizwan; Phillips, John A

2018-03-01

Mitochondrial NAD kinase deficiency (NADK2D, OMIM #615787) is a rare autosomal recessive disorder of NADPH biosynthesis that can cause hyperlysinemia and dienoyl-CoA reductase deficiency (DECRD, OMIM #616034). NADK2 deficiency has been reported in only three unrelated patients. Two had severe, unremitting disease; one died at 4 months and the other at 5 years of age. The third was a 10 year old female with CNS anomalies, ataxia, and incoordination. In two cases mutations in NADK2 have been demonstrated. Here, we report the fourth known case, a 15 year old female with normal intelligence and a mild clinical and biochemical phenotype presumably without DECRD. Her clinical symptoms, which are now stable, became evident at the age of 9 with the onset of decreased visual acuity, bilateral optic atrophy, nystagmus, episodic lower extremity weakness, peripheral neuropathy, and gait abnormalities. Plasma amino acid levels were within normal limits except for mean lysine and proline levels that were 3.7 and 2.5 times the upper limits of normal. Whole exome sequencing (WES) revealed homozygosity for a g.36241900 A>G p. Met1Val start loss mutation in the primary NADK2 transcript (NM_001085411.1) encoding the 442 amino acid isoform. This presumed hypomorphic mutation has not been previously reported and is absent from the v1000GP, EVS, and ExAC databases. Our patient's normal intelligence and stable disease expands the clinical heterogeneity and the prognosis associated with NADK2 deficiency. Our findings also clarify the mechanism underlying NADK2 deficiency and suggest that this disease should be ruled out in cases of hyperlysinemia, especially those with visual loss, and neurological phenotypes. © 2018 Wiley Periodicals, Inc.

The human role in space (THURIS) applications study. Final briefing

NASA Technical Reports Server (NTRS)

Maybee, George W.

1987-01-01

The THURIS (The Human Role in Space) application is an iterative process involving successive assessments of man/machine mixes in terms of performance, cost and technology to arrive at an optimum man/machine mode for the mission application. The process begins with user inputs which define the mission in terms of an event sequence and performance time requirements. The desired initial operational capability date is also an input requirement. THURIS terms and definitions (e.g., generic activities) are applied to the input data converting it into a form which can be analyzed using the THURIS cost model outputs. The cost model produces tabular and graphical outputs for determining the relative cost-effectiveness of a given man/machine mode and generic activity. A technology database is provided to enable assessment of support equipment availability for selected man/machine modes. If technology gaps exist for an application, the database contains information supportive of further investigation into the relevant technologies. The present study concentrated on testing and enhancing the THURIS cost model and subordinate data files and developing a technology database which interfaces directly with the user via technology readiness displays. This effort has resulted in a more powerful, easy-to-use applications system for optimization of man/machine roles. Volume 1 is an executive summary.

MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate Functional Annotation of the Human Genome.

PubMed

Wang, Julia; Al-Ouran, Rami; Hu, Yanhui; Kim, Seon-Young; Wan, Ying-Wooi; Wangler, Michael F; Yamamoto, Shinya; Chao, Hsiao-Tuan; Comjean, Aram; Mohr, Stephanie E; Perrimon, Norbert; Liu, Zhandong; Bellen, Hugo J

2017-06-01

One major challenge encountered with interpreting human genetic variants is the limited understanding of the functional impact of genetic alterations on biological processes. Furthermore, there remains an unmet demand for an efficient survey of the wealth of information on human homologs in model organisms across numerous databases. To efficiently assess the large volume of publically available information, it is important to provide a concise summary of the most relevant information in a rapid user-friendly format. To this end, we created MARRVEL (model organism aggregated resources for rare variant exploration). MARRVEL is a publicly available website that integrates information from six human genetic databases and seven model organism databases. For any given variant or gene, MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and DECIPHER. Importantly, it curates model organism-specific databases to concurrently display a concise summary regarding the human gene homologs in budding and fission yeast, worm, fly, fish, mouse, and rat on a single webpage. Experiment-based information on tissue expression, protein subcellular localization, biological process, and molecular function for the human gene and homologs in the seven model organisms are arranged into a concise output. Hence, rather than visiting multiple separate databases for variant and gene analysis, users can obtain important information by searching once through MARRVEL. Altogether, MARRVEL dramatically improves efficiency and accessibility to data collection and facilitates analysis of human genes and variants by cross-disciplinary integration of 18 million records available in public databases to facilitate clinical diagnosis and basic research. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Strategic Studies Quarterly. Volume 7, Number 4. Winter 2013

DTIC Science & Technology

2013-01-01

databases to bridge the man-machine interface, thereby mak- ing both machines and man more capable of complex thought, independent assessment, and...Edward, “China Steps up Effort to Diversify FX Reserves,” Re- uters, 13 January 2013, http://www.reuters.com/article/2013/01/14/us-china- forex ...of attacks in Israel, Russia, and the United States from 1989 to 2008 (see fig. 2). The analysis combines data from the Global Terrorism Database

[Genetics of tremor].

PubMed

Kuhlenbäumer, G; Hopfner, F

2018-04-01

Tremor is a symptom of many diseases and can constitute a disease of its own: essential tremor. The genetics of essential tremor and differential diagnosis of monogenic diseases with the symptom tremor. Literature search and search of clinical genetics databases, e.g. OMIM, GeneReviews, MDSGene and the German Neurological Society (DGN) guidelines. The genetics of essential tremor remain unresolved in spite of large, adequately powered studies. Tremor is a symptom of differential diagnostic value in many movement disorders. A slight tremor might have been missed or not reported in many descriptions of movement disorders. Progress in the genetics of essential tremor probably requires a more detailed phenotyping allowing stratification into phenotypically defined subgroups. Tremor should always be included in the examination and description of movement disorders even if tremor is not a cardinal symptom. Tremor might be helpful in the differential diagnosis of hereditary dystonia, hereditary ataxia, spastic paraplegia and other movement disorders.

RASopathies: Presentation at the Genome, Interactome, and Phenome Levels.

PubMed

Pevec, Urska; Rozman, Neva; Gorsek, Blaz; Kunej, Tanja

2016-05-01

Clinical symptoms often reflect molecular correlations between mutated proteins. Alignment between interactome and phenome levels reveals new disease genes and connections between previously unrelated diseases. Despite a great potential for novel discoveries, this approach is still rarely used in genomics. In the present study, we analyzed the data of 6 syndromes belonging to the RASopathy class of disorders (RASopathies) and presented them as a model to study associations between genome, interactome, and phenome levels. Causative genes and clinical symptoms were collected from OMIM and NCBI GeneReviews databases for 6 syndromes: Noonan, Noonan syndrome with multiple lentigines, neurofibromatosis type 1, cardiofaciocutaneous, and Legius and Costello syndrome. The STRING tool was used for the identification of protein interactions. Six RASopathy syndromes were found to be associated with 12 causative genes. We constructed an interactome of RASopathy proteins and their neighbors and developed a database of 328 clinical symptoms. The collected data was presented at genome, interactome, and phenome levels and as an integrated network of all 3 data types. The present study provides a baseline for future studies of associations between interactome and phenome in RASopathies and could serve as a novel approach to analyze phenotypically and genetically related diseases.

Encyclopaedia of tumour-associated familial disorders. Part I: from AIMAH to CHIME syndrome

PubMed Central

Sijmons, Rolf H

2008-01-01

Cancer is associated with a wide range of hereditary disorders. Recognizing these disorders in cancer patients may be of great importance for the medical management of both patients and their relatives. Conversely, recognizing the fact that cancer may develop as a complication of a particular hereditary disorder which has already been diagnosed may be important for the same reason. The Familial Cancer Database (FaCD) is a web-based application which has been developed at our department with the intention to assist clinicians and genetic counsellors in making a genetic differential diagnosis in cancer patients, as well as in becoming aware of the tumour spectrum associated with hereditary disorders that have already been diagnosed in their patients. This encyclopaedia is published in parts and discusses the disorders included in the FaCD database in alphabetical order. It lists names, synonyms, OMIM number, mode of inheritance, associated genes, phenotype, clinical discussion and references. The purpose of presenting this encyclopaedia in paper format is simply that we hope that you as clinicians and researchers find it helpful to browse through it and familiarize yourself even better with the scope of genetic disorders that have been associated with increased tumour risk. PMID:19706204

The UCL low-density lipoprotein receptor gene variant database: pathogenicity update

PubMed Central

Futema, Marta; Whittall, Ros; Taylor-Beadling, Alison; Williams, Maggie; den Dunnen, Johan T; Humphries, Steve E

2017-01-01

Background Familial hypercholesterolaemia (OMIM 143890) is most frequently caused by variations in the low-density lipoprotein receptor (LDLR) gene. Predicting whether novel variants are pathogenic may not be straightforward, especially for missense and synonymous variants. In 2013, the Association of Clinical Genetic Scientists published guidelines for the classification of variants, with categories 1 and 2 representing clearly not or unlikely pathogenic, respectively, 3 representing variants of unknown significance (VUS), and 4 and 5 representing likely to be or clearly pathogenic, respectively. Here, we update the University College London (UCL) LDLR variant database according to these guidelines. Methods PubMed searches and alerts were used to identify novel LDLR variants for inclusion in the database. Standard in silico tools were used to predict potential pathogenicity. Variants were designated as class 4/5 only when the predictions from the different programs were concordant and as class 3 when predictions were discordant. Results The updated database (http://www.lovd.nl/LDLR) now includes 2925 curated variants, representing 1707 independent events. All 129 nonsense variants, 337 small frame-shifting and 117/118 large rearrangements were classified as 4 or 5. Of the 795 missense variants, 115 were in classes 1 and 2, 605 in class 4 and 75 in class 3. 111/181 intronic variants, 4/34 synonymous variants and 14/37 promoter variants were assigned to classes 4 or 5. Overall, 112 (7%) of reported variants were class 3. Conclusions This study updates the LDLR variant database and identifies a number of reported VUS where additional family and in vitro studies will be required to confirm or refute their pathogenicity. PMID:27821657

Impact of ionic liquids in aqueous solution on bacterial plasma membranes studied with molecular dynamics simulations.

PubMed

Lim, Geraldine S; Zidar, Jernej; Cheong, Daniel W; Jaenicke, Stephan; Klähn, Marco

2014-09-04

The impact of five different imidazolium-based ionic liquids (ILs) diluted in water on the properties of a bacterial plasma membrane is investigated using molecular dynamics (MD) simulations. Cations considered are 1-octyl-3-methylimidazolium (OMIM), 1-octyloxymethyl-3-methylimidazolium (OXMIM), and 1-tetradecyl-3-methylimidazolium (TDMIM), as well as the anions chloride and lactate. The atomistic model of the membrane bilayer is designed to reproduce the lipid composition of the plasma membrane of Gram-negative Escherichia coli. Spontaneous insertion of cations into the membrane is observed in all ILs. Substantially more insertions of OMIM than of OXMIM occur and the presence of chloride reduces cation insertions compared to lactate. In contrast, anions do not adsorb onto the membrane surface nor diffuse into the bilayer. Once inserted, cations are oriented in parallel to membrane lipids with cation alkyl tails embedded into the hydrophobic membrane core, while the imidazolium-ring remains mostly exposed to the solvent. Such inserted cations are strongly associated with one to two phospholipids in the membrane. The overall order of lipids decreased after OMIM and OXMIM insertions, while on the contrary the order of lipids in the vicinity of TDMIM increased. The short alkyl tails of OMIM and OXMIM generate voids in the bilayer that are filled by curling lipids. This cation induced lipid disorder also reduces the average membrane thickness. This effect is not observed after TDMIM insertions due to the similar length of cation alkyl chain and the fatty acids of the lipids. This lipid-mimicking behavior of inserted TDMIM indicates a high membrane affinity of this cation that could lead to an enhanced accumulation of cations in the membrane over time. Overall, the simulations reveal how cations are inserted into the bacterial membrane and how such insertions change its properties. Moreover, the different roles of cations and anions are highlighted and the fundamental importance of cation alkyl chain length and its functionalization is demonstrated.

An integrated analysis of genes and functional pathways for aggression in human and rodent models.

PubMed

Zhang-James, Yanli; Fernàndez-Castillo, Noèlia; Hess, Jonathan L; Malki, Karim; Glatt, Stephen J; Cormand, Bru; Faraone, Stephen V

2018-06-01

Human genome-wide association studies (GWAS), transcriptome analyses of animal models, and candidate gene studies have advanced our understanding of the genetic architecture of aggressive behaviors. However, each of these methods presents unique limitations. To generate a more confident and comprehensive view of the complex genetics underlying aggression, we undertook an integrated, cross-species approach. We focused on human and rodent models to derive eight gene lists from three main categories of genetic evidence: two sets of genes identified in GWAS studies, four sets implicated by transcriptome-wide studies of rodent models, and two sets of genes with causal evidence from online Mendelian inheritance in man (OMIM) and knockout (KO) mice reports. These gene sets were evaluated for overlap and pathway enrichment to extract their similarities and differences. We identified enriched common pathways such as the G-protein coupled receptor (GPCR) signaling pathway, axon guidance, reelin signaling in neurons, and ERK/MAPK signaling. Also, individual genes were ranked based on their cumulative weights to quantify their importance as risk factors for aggressive behavior, which resulted in 40 top-ranked and highly interconnected genes. The results of our cross-species and integrated approach provide insights into the genetic etiology of aggression.

Disorders of creatine transport and metabolism.

PubMed

Longo, Nicola; Ardon, Orly; Vanzo, Rena; Schwartz, Elizabeth; Pasquali, Marzia

2011-02-15

Creatine is a nitrogen containing compound that serves as an energy shuttle between the mitochondrial sites of ATP production and the cytosol where ATP is utilized. There are two known disorders of creatine synthesis (both transmitted as autosomal recessive traits: arginine: glycine amidinotransferase (AGAT) deficiency; OMIM 602360; and guanidinoacetate methyltransferase (GAMT) deficiency (OMIM 601240)) and one disorder of creatine transport (X-linked recessive SLC6A8 creatine transporter deficiency (OMIM 300036)). All these disorders are characterized by brain creatine deficiency, detectable by magnetic resonance spectroscopy. Affected patients can have mental retardation, hypotonia, autism or behavioral problems and seizures. The diagnosis of these conditions relies on the measurement of plasma and urine creatine and guanidinoacetate. Creatine levels in plasma are reduced in both creatine synthesis defects and guanidinoacetate is increased in GAMT deficiency. The urine creatine/creatinine ratio is elevated in creatine transporter deficiency with normal plasma levels of creatine and guanidinoacetate. The diagnosis is confirmed in all cases by DNA testing or functional studies. Defects of creatine biosynthesis are treated with creatine supplements and, in GAMT deficiency, with ornithine and dietary restriction of arginine through limitation of protein intake. No causal therapy is yet available for creatine transporter deficiency and supplementation with the guanidinoacetate precursors arginine and glycine is being explored. The excellent response to therapy of early identified patients with GAMT or AGAT deficiency candidates these condition for inclusion in newborn screening programs. Copyright © 2011 Wiley-Liss, Inc.

An integrated database-pipeline system for studying single nucleotide polymorphisms and diseases.

PubMed

Yang, Jin Ok; Hwang, Sohyun; Oh, Jeongsu; Bhak, Jong; Sohn, Tae-Kwon

2008-12-12

Studies on the relationship between disease and genetic variations such as single nucleotide polymorphisms (SNPs) are important. Genetic variations can cause disease by influencing important biological regulation processes. Despite the needs for analyzing SNP and disease correlation, most existing databases provide information only on functional variants at specific locations on the genome, or deal with only a few genes associated with disease. There is no combined resource to widely support gene-, SNP-, and disease-related information, and to capture relationships among such data. Therefore, we developed an integrated database-pipeline system for studying SNPs and diseases. To implement the pipeline system for the integrated database, we first unified complicated and redundant disease terms and gene names using the Unified Medical Language System (UMLS) for classification and noun modification, and the HUGO Gene Nomenclature Committee (HGNC) and NCBI gene databases. Next, we collected and integrated representative databases for three categories of information. For genes and proteins, we examined the NCBI mRNA, UniProt, UCSC Table Track and MitoDat databases. For genetic variants we used the dbSNP, JSNP, ALFRED, and HGVbase databases. For disease, we employed OMIM, GAD, and HGMD databases. The database-pipeline system provides a disease thesaurus, including genes and SNPs associated with disease. The search results for these categories are available on the web page http://diseasome.kobic.re.kr/, and a genome browser is also available to highlight findings, as well as to permit the convenient review of potentially deleterious SNPs among genes strongly associated with specific diseases and clinical phenotypes. Our system is designed to capture the relationships between SNPs associated with disease and disease-causing genes. The integrated database-pipeline provides a list of candidate genes and SNP markers for evaluation in both epidemiological and molecular biological approaches to diseases-gene association studies. Furthermore, researchers then can decide semi-automatically the data set for association studies while considering the relationships between genetic variation and diseases. The database can also be economical for disease-association studies, as well as to facilitate an understanding of the processes which cause disease. Currently, the database contains 14,674 SNP records and 109,715 gene records associated with human diseases and it is updated at regular intervals.

Informatics approaches in the Biological Characterization of ...

EPA Pesticide Factsheets

Adverse Outcome Pathways (AOPs) are a conceptual framework to characterize toxicity pathways by a series of mechanistic steps from a molecular initiating event to population outcomes. This framework helps to direct risk assessment research, for example by aiding in computational prioritization of chemicals, genes, and tissues relevant to an adverse health outcome. We have designed and implemented a computational workflow to access a wealth of public data relating genes, chemicals, diseases, pathways, and species, to provide a biological context for putative AOPs. We selected three AOP case studies: ER/Aromatase Antagonism Leading to Reproductive Dysfunction, AHR1 Activation Leading to Cardiotoxicity, and AChE Inhibition Leading to Acute Mortality, and deduced a taxonomic range of applicability for each AOP. We developed computational tools to automatically access and analyze the pathway activity of AOP-relevant protein orthologs, finding broad similarity among vertebrate species for the ER/Aromatase and AHR1 AOPs, and similarity extending to invertebrate animal species for AChE inhibition. Additionally, we used public gene expression data to find groups of highly co-expressed genes, and compared those groups across organisms. To interpret these findings at a higher level of biological organization, we created the AOPdb, a relational database that mines results from sources including NCBI, KEGG, Reactome, CTD, and OMIM. This multi-source database connects genes,

Task-Oriented, Naturally Elicited Speech (TONE) Database for the Force Requirements Expert System, Hawaii (FRESH)

DTIC Science & Technology

1988-09-01

Group Subgroup Command and control; Computational linguistics; expert system voice recognition; man- machine interface; U.S. Government 19 Abstract...simulates the characteristics of FRESH on a smaller scale. This study assisted NOSC in developing a voice-recognition, man- machine interface that could...scale. This study assisted NOSC in developing a voice-recogni- tion, man- machine interface that could be used with TONE and upgraded at a later date

Genetics Home Reference: surfactant dysfunction

MedlinePlus

... Infant ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (4 links) SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 1 SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 2 ...

Genetics Home Reference: biotin-thiamine-responsive basal ganglia disease

MedlinePlus

... link) Biotin-Thiamine-Responsive Basal Ganglia Disease Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) THIAMINE METABOLISM DYSFUNCTION SYNDROME 2 (BIOTIN- OR THIAMINE-RESPONSIVE TYPE) ...

Genetics Home Reference: prostate cancer

MedlinePlus

... prostate cancer Genetic Testing Registry: Prostate cancer aggressiveness quantitative trait locus on chromosome 19 Genetic Testing Registry: ... OMIM (25 links) PROSTATE CANCER PROSTATE CANCER AGGRESSIVENESS QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 19 PROSTATE CANCER ANTIGEN ...

Genetics Home Reference: GRACILE syndrome

MedlinePlus

... University of Utah Eccles Health Sciences Library: Iron Metabolism Patient Support and Advocacy Resources (1 link) Climb: National Information Centre for Metabolic Diseases Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

A previously undescribed syndrome combining fibular agenesis/hypoplasia, oligodactylous clubfeet, anonychia/ungual hypoplasia, and other defects.

PubMed

Santos, Silvana C; Pardono, Eliete; Ferreira da Costa, Maria Ione; de Melo, Aurea Nogueira; Graciani, Zodja; de Albuquerque e Souza, Alessandra Cavalcanti; Lezirovitz, Karina; Thiele-Aguiar, Renata Soares; Mingroni-Netto, Regina Célia; Opitz, John M; Kok, Fernando; Otto, Paulo A

2008-12-15

We describe an apparently new genetic syndrome in six members of a family living in a remote area in Northeastern Brazil. This syndrome comprises: short stature due to a marked decrease in the length of the lower limbs (predominantly mesomelic with fibular agenesis/marked hypoplasia), grossly malformed/deformed clubfeet with severe oligodactyly, upper limbs with acromial dimples and variable motion limitation of the forearms and/or hands, severe nail hypoplasia/anonychia sometimes associated with mild brachydactyly and occasionally with pre-axial polydactyly. This syndrome is apparently distinct from the syndrome of brachydactyly-ectrodactyly with fibular aplasia or hypoplasia (OMIM 113310), the syndrome of fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly (OMIM 228930), and from other previously described conditions exhibiting fibular agenesis/hypoplasia. Copyright (c) 2008 Wiley-Liss, Inc.

Genetics Home Reference: adenylosuccinate lyase deficiency

MedlinePlus

... its chemical cousin RNA, and molecules such as ATP that serve as energy sources in the cell. ... For People With Intellectual and Developmental Disabilities Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Genetics Home Reference: histiocytosis-lymphadenopathy plus syndrome

MedlinePlus

... its chemical cousin RNA, and molecules such as ATP and GTP, which serve as energy sources in ... Skin Association Histiocytosis Association: Rosai-Dorfman Disease Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Genetics Home Reference: Arts syndrome

MedlinePlus

... its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in ... Syndrome ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Genetics Home Reference: motion sickness

MedlinePlus

... motion, particularly traveling in a car, bus, train, airplane, or boat. Amusement park rides, skiing, and virtual ... Association ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Semi-automated literature mining to identify putative biomarkers of disease from multiple biofluids

PubMed Central

2014-01-01

Background Computational methods for mining of biomedical literature can be useful in augmenting manual searches of the literature using keywords for disease-specific biomarker discovery from biofluids. In this work, we develop and apply a semi-automated literature mining method to mine abstracts obtained from PubMed to discover putative biomarkers of breast and lung cancers in specific biofluids. Methodology A positive set of abstracts was defined by the terms ‘breast cancer’ and ‘lung cancer’ in conjunction with 14 separate ‘biofluids’ (bile, blood, breastmilk, cerebrospinal fluid, mucus, plasma, saliva, semen, serum, synovial fluid, stool, sweat, tears, and urine), while a negative set of abstracts was defined by the terms ‘(biofluid) NOT breast cancer’ or ‘(biofluid) NOT lung cancer.’ More than 5.3 million total abstracts were obtained from PubMed and examined for biomarker-disease-biofluid associations (34,296 positive and 2,653,396 negative for breast cancer; 28,355 positive and 2,595,034 negative for lung cancer). Biological entities such as genes and proteins were tagged using ABNER, and processed using Python scripts to produce a list of putative biomarkers. Z-scores were calculated, ranked, and used to determine significance of putative biomarkers found. Manual verification of relevant abstracts was performed to assess our method’s performance. Results Biofluid-specific markers were identified from the literature, assigned relevance scores based on frequency of occurrence, and validated using known biomarker lists and/or databases for lung and breast cancer [NCBI’s On-line Mendelian Inheritance in Man (OMIM), Cancer Gene annotation server for cancer genomics (CAGE), NCBI’s Genes & Disease, NCI’s Early Detection Research Network (EDRN), and others]. The specificity of each marker for a given biofluid was calculated, and the performance of our semi-automated literature mining method assessed for breast and lung cancer. Conclusions We developed a semi-automated process for determining a list of putative biomarkers for breast and lung cancer. New knowledge is presented in the form of biomarker lists; ranked, newly discovered biomarker-disease-biofluid relationships; and biomarker specificity across biofluids. PMID:25379168

[MVK gene abnormality and new approach to treatment of hyper IgD syndrome and periodic fever syndrome].

PubMed

Naruto, Takuya

2007-04-01

Hyper IgD and periodic fever syndrome (HIDS; OMIM 260920) is one of the hereditary autoinflammatory syndromes characterized by recurrent episodes of fever and inflammation.. HIDS is an autosomal recessive disorder characterized by recurrent fever attacks in early childhood. HIDS caused by mevalonate kinase (MK) mutations, also that is the gene of mevalonic aciduria (OMIM 251170). During febrile episodes, urinary mevalonate concentrations were found to be significantly elevated in patients. Diagnosis of HIDS was retrieving gene or measurement of the enzyme activity in peripheral blood lymphocyte in general. This of HIDS is an activity decline of MK, and a complete deficiency of MK becomes a mevalonic aciduria with a nervous symptom. The relation between the fever and inflammation of mevalonate or isoprenoid products are uncertain. The therapy attempt with statins, which is inhibited the next enzyme after HMG-CoA reductase, or inhibit the proinflammatory cytokines.

5p13 microduplication syndrome: a new case and better clinical definition of the syndrome.

PubMed

Novara, Francesca; Alfei, Enrico; D'Arrigo, Stefano; Pantaleoni, Chiara; Beri, Silvana; Achille, Valentina; Sciacca, Francesca L; Giorda, Roberto; Zuffardi, Orsetta; Ciccone, Roberto

2013-01-01

Chromosome 5p13 duplication syndrome (OMIM #613174), a contiguous gene syndrome involving duplication of several genes on chromosome 5p13 including NIPBL (OMIM 608667), has been described in rare patients with developmental delay and learning disability, behavioral problems and peculiar facial dysmorphisms. 5p13 duplications described so far present with variable sizes, from 0.25 to 13.6 Mb, and contain a variable number of genes. Here we report another patient with 5p13 duplication syndrome including NIPBL gene only. Proband's phenotype overlapped that reported in patients with 5p13 microduplication syndrome and especially that of subjects with smaller duplications. Moreover, we better define genotype-phenotype relationship associated with this duplication and confirmed that NIPBL was likely the major dosage sensitive gene for the 5p13 microduplication phenotype. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Perthes disease: A new finding in Floating-Harbor syndrome.

PubMed

Milani, Donatella; Scuvera, Giulietta; Gatti, Marta; Tolva, Gianluca; Bonarrigo, Francesca; Esposito, Susanna; Gervasini, Cristina

2018-03-01

Floating-Harbor Syndrome (FHS; OMIM #136140) is an ultra-rare autosomal dominant genetic condition characterized by expressive language delay, short stature with delayed bone mineralization, a triangular face with a prominent nose, and deep-set eyes, and hand anomalies. First reported in 1973, FHS is associated with mutations in the SRCAP gene, which encodes SNF2-related CREBBP activator protein. Mutations in the CREBBP gene cause Rubinstein-Taybi Syndrome (RSTS; OMIM #180849, #613684), another rare disease characterized by broad thumbs and halluces, facial dysmorphisms, short stature, and intellectual disability, which has a phenotypic overlap with FHS. We describe a case of FHS associated with a novel SRCAP mutation and characterized by Perthes disease, a skeletal anomaly described in approximately 3% of patients with RSTS. Thus Perthes disease can be added to the list of clinical features that overlap between FHS and RSTS. © 2018 Wiley Periodicals, Inc.

End-User Use of Data Base Query Language: Pros and Cons.

ERIC Educational Resources Information Center

Nicholes, Walter

1988-01-01

Man-machine interface, the concept of a computer "query," a review of database technology, and a description of the use of query languages at Brigham Young University are discussed. The pros and cons of end-user use of database query languages are explored. (Author/MLW)

GM2 Activator Deficiency Caused by a Homozygous Exon 2 Deletion in GM2A.

PubMed

Hall, Patricia L; Laine, Regina; Alexander, John J; Ankala, Arunkanth; Teot, Lisa A; Lidov, Hart G W; Anselm, Irina

2018-01-01

GM2 activator (GM2A) deficiency (OMIM 613109) is a rare lysosomal storage disorder, with onset typically in infancy or early childhood. Clinically, it is almost indistinguishable from Tay-Sachs disease (OMIM 272800) or Sandhoff disease (OMIM 268800); however, traditionally available biochemical screening tests will most likely reveal normal results. We report a 2-year-old male with initially normal development until the age of 9 months, when he presented with developmental delay and regression. Workup at that time was unrevealing; at 15 months, he had abnormal brain MRI findings and a cherry red spot on ophthalmological examination. Family history and all laboratory studies were uninformative. The combination of a cherry red spot and developmental regression was strongly suggestive of a lysosomal storage disorder. Sequence analysis of GM2A did not reveal any pathogenic variants; however, exon 2 of GM2A could not be amplified by PCR, raising suspicion for a large, homozygous deletion. Subsequent copy number analysis confirmed a homozygous deletion of exon 2 in GM2A. This is the first reported case of GM2A deficiency being caused by a whole exon deletion. We describe previously unreported electron microscopy findings in this disease, thus expanding the clinical and variant spectrum for GM2 activator deficiency. These findings demonstrate the increased degree of suspicion required for diagnosis of this rare disorder. Brief Summary: This case of GM2 activator deficiency was caused by a homozygous deletion in GM2A, demonstrating the need to include exon level copy number analysis in any workup to fully exclude this disorder.

Genetics Home Reference: microphthalmia with linear skin defects syndrome

MedlinePlus

... oxidative phosphorylation , by which mitochondria generate adenosine triphosphate (ATP), the cell's main energy source. It also plays ... Syndrome ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Genetics Home Reference: Holt-Oram syndrome

MedlinePlus

... PubMed OMIM: HOLT-ORAM SYNDROME Hatcher CJ, McDermott DA. Using the TBX5 transcription factor to grow and ... 2002;67:115-20. Citation on PubMed McDermott DA, Bressan MC, He J, Lee JS, Aftimos S, Brueckner ...

One approach to design of speech emotion database

NASA Astrophysics Data System (ADS)

Uhrin, Dominik; Chmelikova, Zdenka; Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav

2016-05-01

This article describes a system for evaluating the credibility of recordings with emotional character. Sound recordings form Czech language database for training and testing systems of speech emotion recognition. These systems are designed to detect human emotions in his voice. The emotional state of man is useful in the security forces and emergency call service. Man in action (soldier, police officer and firefighter) is often exposed to stress. Information about the emotional state (his voice) will help to dispatch to adapt control commands for procedure intervention. Call agents of emergency call service must recognize the mental state of the caller to adjust the mood of the conversation. In this case, the evaluation of the psychological state is the key factor for successful intervention. A quality database of sound recordings is essential for the creation of the mentioned systems. There are quality databases such as Berlin Database of Emotional Speech or Humaine. The actors have created these databases in an audio studio. It means that the recordings contain simulated emotions, not real. Our research aims at creating a database of the Czech emotional recordings of real human speech. Collecting sound samples to the database is only one of the tasks. Another one, no less important, is to evaluate the significance of recordings from the perspective of emotional states. The design of a methodology for evaluating emotional recordings credibility is described in this article. The results describe the advantages and applicability of the developed method.

CaveMan Enterprise version 1.0 Software Validation and Verification.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hart, David

The U.S. Department of Energy Strategic Petroleum Reserve stores crude oil in caverns solution-mined in salt domes along the Gulf Coast of Louisiana and Texas. The CaveMan software program has been used since the late 1990s as one tool to analyze pressure mea- surements monitored at each cavern. The purpose of this monitoring is to catch potential cavern integrity issues as soon as possible. The CaveMan software was written in Microsoft Visual Basic, and embedded in a Microsoft Excel workbook; this method of running the CaveMan software is no longer sustainable. As such, a new version called CaveMan Enter- prisemore » has been developed. CaveMan Enterprise version 1.0 does not have any changes to the CaveMan numerical models. CaveMan Enterprise represents, instead, a change from desktop-managed work- books to an enterprise framework, moving data management into coordinated databases and porting the numerical modeling codes into the Python programming language. This document provides a report of the code validation and verification testing.« less

Genetics Home Reference: sitosterolemia

MedlinePlus

... Sitosterolemia ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) SITOSTEROLEMIA Sources for This Page Berge KE. Sitosterolemia: a gateway to new knowledge about cholesterol metabolism. Ann Med. 2003;35(7):502-11. Review. ...

Genetics Home Reference: isolated sulfite oxidase deficiency

MedlinePlus

... Metabolic Disorders (CLIMB) March of Dimes: Amino Acid Metabolism Disorders The Compassionate Friends GeneReviews (1 link) Isolated Sulfite Oxidase Deficiency ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Spectrum of PORCN mutations in Focal Dermal Hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome (OMIM 305600), is a genetic disorder that affects multiple organ systems early in development. Features of FDH include skin abnormalities, (hypoplasia, atrophy, linear pigmentation, and herniation of fat through dermal defects); papillomas...

Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

NASA Astrophysics Data System (ADS)

Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

2015-06-01

Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

Molecular and clinical studies of X-linked deafness among Pakistani families.

PubMed

Waryah, Ali M; Ahmed, Zubair M; Bhinder, Munir A; Binder, Munir A; Choo, Daniel I; Sisk, Robert A; Shahzad, Mohsin; Khan, Shaheen N; Friedman, Thomas B; Riazuddin, Sheikh; Riazuddin, Saima

2011-07-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis.

Laplacian normalization and random walk on heterogeneous networks for disease-gene prioritization.

PubMed

Zhao, Zhi-Qin; Han, Guo-Sheng; Yu, Zu-Guo; Li, Jinyan

2015-08-01

Random walk on heterogeneous networks is a recently emerging approach to effective disease gene prioritization. Laplacian normalization is a technique capable of normalizing the weight of edges in a network. We use this technique to normalize the gene matrix and the phenotype matrix before the construction of the heterogeneous network, and also use this idea to define the transition matrices of the heterogeneous network. Our method has remarkably better performance than the existing methods for recovering known gene-phenotype relationships. The Shannon information entropy of the distribution of the transition probabilities in our networks is found to be smaller than the networks constructed by the existing methods, implying that a higher number of top-ranked genes can be verified as disease genes. In fact, the most probable gene-phenotype relationships ranked within top 3 or top 5 in our gene lists can be confirmed by the OMIM database for many cases. Our algorithms have shown remarkably superior performance over the state-of-the-art algorithms for recovering gene-phenotype relationships. All Matlab codes can be available upon email request. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular and Clinical Studies of X-linked Deafness Among Pakistani Families

PubMed Central

Waryah, Ali M.; Ahmed, Zubair M.; Choo, Daniel I.; Sisk, Robert A.; Binder, Munir A.; Shahzad, Mohsin; Khan, Shaheen N.; Friedman, Thomas B.; Riazuddin, Sheikh; Riazuddin, Saima

2011-01-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132, PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild to profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling, and molecular epidemiology of hearing loss among Pakistanis. PMID:21633365

Genetics Home Reference: hereditary hemorrhagic telangiectasia

MedlinePlus

... Central OMIM: JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic ... 10.1097/GIM.0b013e3182136d32. Review. Citation on PubMed McDonald J, Wooderchak-Donahue W, VanSant Webb C, Whitehead ...

Protein-protein interaction analysis of Alzheimer`s disease and NAFLD based on systems biology methods unhide common ancestor pathways.

PubMed

Karbalaei, Reza; Allahyari, Marzieh; Rezaei-Tavirani, Mostafa; Asadzadeh-Aghdaei, Hamid; Zali, Mohammad Reza

2018-01-01

Analysis reconstruction networks from two diseases, NAFLD and Alzheimer`s diseases and their relationship based on systems biology methods. NAFLD and Alzheimer`s diseases are two complex diseases, with progressive prevalence and high cost for countries. There are some reports on relation and same spreading pathways of these two diseases. In addition, they have some similar risk factors, exclusively lifestyle such as feeding, exercises and so on. Therefore, systems biology approach can help to discover their relationship. DisGeNET and STRING databases were sources of disease genes and constructing networks. Three plugins of Cytoscape software, including ClusterONE, ClueGO and CluePedia, were used to analyze and cluster networks and enrichment of pathways. An R package used to define best centrality method. Finally, based on degree and Betweenness, hubs and bottleneck nodes were defined. Common genes between NAFLD and Alzheimer`s disease were 190 genes that used construct a network with STRING database. The resulting network contained 182 nodes and 2591 edges and comprises from four clusters. Enrichment of these clusters separately lead to carbohydrate metabolism, long chain fatty acid and regulation of JAK-STAT and IL-17 signaling pathways, respectively. Also seven genes selected as hub-bottleneck include: IL6, AKT1, TP53, TNF, JUN, VEGFA and PPARG. Enrichment of these proteins and their first neighbors in network by OMIM database lead to diabetes and obesity as ancestors of NAFLD and AD. Systems biology methods, specifically PPI networks, can be useful for analyzing complicated related diseases. Finding Hub and bottleneck proteins should be the goal of drug designing and introducing disease markers.

Synthesis of flower-like Boehmite (γ-AlOOH) via a one-step ionic liquid-assisted hydrothermal route

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Zhe, E-mail: tangzhe1983@163.com; Liang, Jilei, E-mail: liangjilei_httplan@126.com; Li, Xuehui, E-mail: lxhhmx@163.com

A simple and novel synthesis process, one-step ionic liquid-assisted hydrothermal synthesis route, has been developed in the work to synthesize Bohemithe (γ-AlOOH) with flower-like structure. The samples were characterized by X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscope (SEM). Ionic liquid [Omim]{sup +}Cl{sup −}, as a template, plays an important role in the morphology and pore structure of the products due to its strong interactions with reaction particles. With the increase in the dosage of ionic liquid [Omim]{sup +}Cl{sup −}, the morphology of the γ-AlOOH was changed from initial bundles of nanosheets (without ionic liquid) intomore » final well-developed monodispersed 3D flower-like architectures ([Omim]{sup +}Cl{sup −}=72 mmol). The pore structure was also altered gradually from initial disordered slit-like pore into final relatively ordered ink-bottle pore. Furthermore, the proposed formation mechanism and other influencing factors such as reaction temperature and urea on formation and morphology of the γ-AlOOH have also been investigated. - Graphical abstract: The flower-like γ-AlOOH architectures composed by nanosheets with narrow size distribution (1.6–2.2 μm) and uniform pore size (6.92 nm) have been synthesized via a one-step ionic liquid-assisted hydrothermal route. - Highlights: • The γ-AlOOH microflowers were synthesized via an ionic liquid-assisted hydrothermal route. • Ionic liquid plays an important role on the morphology and porous structure of the products. • Ionic liquid can be easily removed from the products and reused in recycling experiments. • A “aggregation–recrystallization–Ostwald Ripening“formation mechanism may occur.« less

Genetics Home Reference: Weyers acrofacial dysostosis

MedlinePlus

... Ellis-van Creveld Syndrome Resource list from the University of Kansas Medical Center: Dwarfism / Short Stature Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) WEYERS ACROFACIAL DYSOSTOSIS Sources for This Page Howard TD, Guttmacher AE, McKinnon W, Sharma M, McKusick ...

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome

PubMed Central

Di Gioia, Silvio Alessandro; Connors, Samantha; Matsunami, Norisada; Cannavino, Jessica; Rose, Matthew F.; Gilette, Nicole M.; Artoni, Pietro; de Macena Sobreira, Nara Lygia; Chan, Wai-Man; Webb, Bryn D.; Robson, Caroline D.; Cheng, Long; Van Ryzin, Carol; Ramirez-Martinez, Andres; Mohassel, Payam; Leppert, Mark; Scholand, Mary Beth; Grunseich, Christopher; Ferreira, Carlos R.; Hartman, Tyler; Hayes, Ian M.; Morgan, Tim; Markie, David M.; Fagiolini, Michela; Swift, Amy; Chines, Peter S.; Speck-Martins, Carlos E.; Collins, Francis S.; Jabs, Ethylin Wang; Bönnemann, Carsten G.; Olson, Eric N.; Andrews, Caroline V.; Barry, Brenda J.; Hunter, David G.; Mackinnon, Sarah E.; Shaaban, Sherin; Erazo, Monica; Frempong, Tamiesha; Hao, Ke; Naidich, Thomas P.; Rucker, Janet C.; Zhang, Zhongyang; Biesecker, Barbara B.; Bonnycastle, Lori L.; Brewer, Carmen C.; Brooks, Brian P.; Butman, John A.; Chien, Wade W.; Farrell, Kathleen; FitzGibbon, Edmond J.; Gropman, Andrea L.; Hutchinson, Elizabeth B.; Jain, Minal S.; King, Kelly A.; Lehky, Tanya J.; Lee, Janice; Liberton, Denise K.; Narisu, Narisu; Paul, Scott M.; Sadeghi, Neda; Snow, Joseph; Solomon, Beth; Summers, Angela; Toro, Camilo; Thurm, Audrey; Zalewski, Christopher K.; Carey, John C.; Robertson, Stephen P.; Manoli, Irini; Engle, Elizabeth C.

2017-01-01

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymkinsT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits. PMID:28681861

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome.

PubMed

Di Gioia, Silvio Alessandro; Connors, Samantha; Matsunami, Norisada; Cannavino, Jessica; Rose, Matthew F; Gilette, Nicole M; Artoni, Pietro; de Macena Sobreira, Nara Lygia; Chan, Wai-Man; Webb, Bryn D; Robson, Caroline D; Cheng, Long; Van Ryzin, Carol; Ramirez-Martinez, Andres; Mohassel, Payam; Leppert, Mark; Scholand, Mary Beth; Grunseich, Christopher; Ferreira, Carlos R; Hartman, Tyler; Hayes, Ian M; Morgan, Tim; Markie, David M; Fagiolini, Michela; Swift, Amy; Chines, Peter S; Speck-Martins, Carlos E; Collins, Francis S; Jabs, Ethylin Wang; Bönnemann, Carsten G; Olson, Eric N; Carey, John C; Robertson, Stephen P; Manoli, Irini; Engle, Elizabeth C

2017-07-06

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk insT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits.

Data supporting mitochondrial morphological changes by SPG13-associated HSPD1 mutants.

PubMed

Miyamoto, Yuki; Megumi, Funakoshi-Tago; Hasegawa, Nanami; Eguchi, Takahiro; Tanoue, Akito; Tamura, Hiroomi; Yamauchi, Junji

2016-03-01

The data is related to the research article entitled "Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics" [1]. In addition to hypomyelinating leukodystrophy (HLD) 4 (OMIM no. 612233), it is known that spastic paraplegia (SPG) 13 (OMIM no. 605280) is caused by HSPD1's amino acid mutation. Two amino acid mutations Val-98-to-Ile (V98I) and Gln-461-to-Glu (Q461E) are associated with SPG13 [2]. In order to investigate the effects of HSPD1's V98I or Q461E mutant on mitochondrial morphological changes, we transfected each of the respective mutant-encoding genes into Cos-7 cells. Either of V98I or Q461E mutant exhibited increased number of mitochondria and short length mitochondrial morphologies. Using MitoTracker dye-incorporating assay, decreased mitochondrial membrane potential was also observed in both cases. The data described here supports that SPG13-associated HSPD1 mutant participates in causing aberrant mitochondrial morphological changes with decreased activities.

The Cognitive and Behavioural Phenotype of Roifman Syndrome

ERIC Educational Resources Information Center

de Vries, P. J.; McCartney, D. L.; McCartney, E.; Woolf, D.; Wozencroft, D.

2006-01-01

Background: Roifman syndrome (OMIM 300258) is a multi-system disorder with a physical phenotype that includes B-cell immunodeficiency, intra-uterine and postnatal growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy and characteristic facial dysmorphism. So far, six cases, all boys, have been reported in the literature. Roifman…

Genetics Home Reference: lipoid proteinosis

MedlinePlus

... Problems National Alliance on Mental Illness Pediatric Dermatology Research Alliance GeneReviews (1 link) Lipoid Proteinosis Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) LIPOID PROTEINOSIS OF URBACH AND WIETHE MedGen (1 link) Lipid proteinosis Sources for This Page Callizo M, Ibáñez- ...

Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: a genome-wide association study.

PubMed

Naj, Adam C; Jun, Gyungah; Reitz, Christiane; Kunkle, Brian W; Perry, William; Park, Yo Son; Beecham, Gary W; Rajbhandary, Ruchita A; Hamilton-Nelson, Kara L; Wang, Li-San; Kauwe, John S K; Huentelman, Matthew J; Myers, Amanda J; Bird, Thomas D; Boeve, Bradley F; Baldwin, Clinton T; Jarvik, Gail P; Crane, Paul K; Rogaeva, Ekaterina; Barmada, M Michael; Demirci, F Yesim; Cruchaga, Carlos; Kramer, Patricia L; Ertekin-Taner, Nilufer; Hardy, John; Graff-Radford, Neill R; Green, Robert C; Larson, Eric B; St George-Hyslop, Peter H; Buxbaum, Joseph D; Evans, Denis A; Schneider, Julie A; Lunetta, Kathryn L; Kamboh, M Ilyas; Saykin, Andrew J; Reiman, Eric M; De Jager, Philip L; Bennett, David A; Morris, John C; Montine, Thomas J; Goate, Alison M; Blacker, Deborah; Tsuang, Debby W; Hakonarson, Hakon; Kukull, Walter A; Foroud, Tatiana M; Martin, Eden R; Haines, Jonathan L; Mayeux, Richard P; Farrer, Lindsay A; Schellenberg, Gerard D; Pericak-Vance, Margaret A; Albert, Marilyn S; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Barber, Robert; Barnes, Lisa L; Beach, Thomas G; Becker, James T; Beekly, Duane; Bigio, Eileen H; Bowen, James D; Boxer, Adam; Burke, James R; Cairns, Nigel J; Cantwell, Laura B; Cao, Chuanhai; Carlson, Chris S; Carney, Regina M; Carrasquillo, Minerva M; Carroll, Steven L; Chui, Helena C; Clark, David G; Corneveaux, Jason; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; DeKosky, Steven T; Dick, Malcolm; Dickson, Dennis W; Duara, Ranjan; Faber, Kelley M; Fallon, Kenneth B; Farlow, Martin R; Ferris, Steven; Frosch, Matthew P; Galasko, Douglas R; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H; Ghetti, Bernardino; Gilbert, John R; Glass, Jonathan D; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Head, Elizabeth; Honig, Lawrence S; Hulette, Christine M; Hyman, Bradley T; Jicha, Gregory A; Jin, Lee-Way; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Koo, Edward H; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Ge; Lieberman, Andrew P; Lin, Chiao-Feng; Lopez, Oscar L; Lyketsos, Constantine G; Mack, Wendy J; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Murrell, Jill R; Olichney, John M; Pankratz, Vernon S; Parisi, Joseph E; Paulson, Henry L; Peskind, Elaine; Petersen, Ronald C; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reisberg, Barry; Ringman, John M; Roberson, Erik D; Rosen, Howard J; Rosenberg, Roger N; Sano, Mary; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Valladares, Otto; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vardarajan, Badri N; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Williamson, Jennifer; Wishnek, Sarah; Woltjer, Randall L; Wright, Clinton B; Younkin, Steven G; Yu, Chang-En; Yu, Lei

2014-11-01

Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants. To investigate the effects of known Alzheimer disease risk loci in modifying AAO and to estimate their cumulative effect on AAO variation using data from genome-wide association studies in the Alzheimer Disease Genetics Consortium. The Alzheimer Disease Genetics Consortium comprises 14 case-control, prospective, and family-based data sets with data on 9162 participants of white race/ethnicity with Alzheimer disease occurring after age 60 years who also had complete AAO information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single-nucleotide polymorphisms most significantly associated with risk at 10 confirmed LOAD loci were examined in linear modeling of AAO, and individual data set results were combined using a random-effects, inverse variance-weighted meta-analysis approach to determine whether they contribute to variation in AAO. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. Age at disease onset abstracted from medical records among participants with LOAD diagnosed per standard criteria. Analysis confirmed the association of APOE with earlier AAO (P = 3.3 × 10(-96)), with associations in CR1 (rs6701713, P = 7.2 × 10(-4)), BIN1 (rs7561528, P = 4.8 × 10(-4)), and PICALM (rs561655, P = 2.2 × 10(-3)) reaching statistical significance (P < .005). Risk alleles individually reduced AAO by 3 to 6 months. Burden analyses demonstrated that APOE contributes to 3.7% of the variation in AAO (R(2) = 0.256) over baseline (R(2) = 0.221), whereas the other 9 loci together contribute to 2.2% of the variation (R(2) = 0.242). We confirmed an association of APOE (OMIM 107741) variants with AAO among affected participants with LOAD and observed novel associations of CR1 (OMIM 120620), BIN1 (OMIM 601248), and PICALM (OMIM 603025) with AAO. In contrast to earlier hypothetical modeling, we show that the combined effects of Alzheimer disease risk variants on AAO are on the scale of, but do not exceed, the APOE effect. While the aggregate effects of risk loci on AAO may be significant, additional genetic contributions to AAO are individually likely to be small.

Genetics Home Reference: ichthyosis with confetti

MedlinePlus

... from the University of Kansas Medical Center: Ichthyosis Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ... 1;330(6000):94-7. doi: 10.1126/science.1192280. Epub 2010 Aug 26. Citation on PubMed or Free article on PubMed Central Krunic AL, Palcesky D, Busbey S, ...

Non-coding, mRNA-like RNAs database Y2K.

PubMed

Erdmann, V A; Szymanski, M; Hochberg, A; Groot, N; Barciszewski, J

2000-01-01

In last few years much data has accumulated on various non-translatable RNA transcripts that are synthesised in different cells. They are lacking in protein coding capacity and it seems that they work mainly or exclusively at the RNA level. All known non-coding RNA transcripts are collected in the database: http://www. man.poznan.pl/5SData/ncRNA/index.html

Non-coding, mRNA-like RNAs database Y2K

PubMed Central

Erdmann, Volker A.; Szymanski, Maciej; Hochberg, Abraham; Groot, Nathan de; Barciszewski, Jan

2000-01-01

In last few years much data has accumulated on various non-translatable RNA transcripts that are synthesised in different cells. They are lacking in protein coding capacity and it seems that they work mainly or exclusively at the RNA level. All known non-coding RNA transcripts are collected in the database: http://www.man.poznan.pl/5SData/ncRNA/index.html PMID:10592224

Development and characterization of a 3D high-resolution terrain database

NASA Astrophysics Data System (ADS)

Wilkosz, Aaron; Williams, Bryan L.; Motz, Steve

2000-07-01

A top-level description of methods used to generate elements of a high resolution 3D characterization database is presented. The database elements are defined as ground plane elevation map, vegetation height elevation map, material classification map, discrete man-made object map, and temperature radiance map. The paper will cover data collection by means of aerial photography, techniques of soft photogrammetry used to derive the elevation data, and the methodology followed to generate the material classification map. The discussion will feature the development of the database elements covering Fort Greely, Alaska. The developed databases are used by the US Army Aviation and Missile Command to evaluate the performance of various missile systems.

The Liverwort Contains a Lectin That Is Structurally and Evolutionary Related to the Monocot Mannose-Binding Lectins1

PubMed Central

Peumans, Willy J.; Barre, Annick; Bras, Julien; Rougé, Pierre; Proost, Paul; Van Damme, Els J.M.

2002-01-01

A mannose (Man)-binding lectin has been isolated and characterized from the thallus of the liverwort Marchantia polymorpha. N-terminal sequencing indicated that the M. polymorpha agglutinin (Marpola) shares sequence similarity with the superfamily of monocot Man-binding lectins. Searches in the databases yielded expressed sequence tags encoding Marpola. Sequence analysis, molecular modeling, and docking experiments revealed striking structural similarities between Marpola and the monocot Man-binding lectins. Activity and specificity studies further indicated that Marpola is a much stronger agglutinin than the Galanthus nivalis agglutinin and exhibits a preference for methylated Man and glucose, which is unprecedented within the family of monocot Man-binding lectins. The discovery of Marpola allows us, for the first time, to corroborate the evolutionary relationship between a lectin from a lower plant and a well-established lectin family from flowering plants. In addition, the identification of Marpola sheds a new light on the molecular evolution of the superfamily of monocot Man-binding lectins. Beside evolutionary considerations, the occurrence of a G. nivalis agglutinin homolog in a lower plant necessitates the rethinking of the physiological role of the whole family of monocot Man-binding lectins. PMID:12114560

Disease gene prioritization by integrating tissue-specific molecular networks using a robust multi-network model.

PubMed

Ni, Jingchao; Koyuturk, Mehmet; Tong, Hanghang; Haines, Jonathan; Xu, Rong; Zhang, Xiang

2016-11-10

Accurately prioritizing candidate disease genes is an important and challenging problem. Various network-based methods have been developed to predict potential disease genes by utilizing the disease similarity network and molecular networks such as protein interaction or gene co-expression networks. Although successful, a common limitation of the existing methods is that they assume all diseases share the same molecular network and a single generic molecular network is used to predict candidate genes for all diseases. However, different diseases tend to manifest in different tissues, and the molecular networks in different tissues are usually different. An ideal method should be able to incorporate tissue-specific molecular networks for different diseases. In this paper, we develop a robust and flexible method to integrate tissue-specific molecular networks for disease gene prioritization. Our method allows each disease to have its own tissue-specific network(s). We formulate the problem of candidate gene prioritization as an optimization problem based on network propagation. When there are multiple tissue-specific networks available for a disease, our method can automatically infer the relative importance of each tissue-specific network. Thus it is robust to the noisy and incomplete network data. To solve the optimization problem, we develop fast algorithms which have linear time complexities in the number of nodes in the molecular networks. We also provide rigorous theoretical foundations for our algorithms in terms of their optimality and convergence properties. Extensive experimental results show that our method can significantly improve the accuracy of candidate gene prioritization compared with the state-of-the-art methods. In our experiments, we compare our methods with 7 popular network-based disease gene prioritization algorithms on diseases from Online Mendelian Inheritance in Man (OMIM) database. The experimental results demonstrate that our methods recover true associations more accurately than other methods in terms of AUC values, and the performance differences are significant (with paired t-test p-values less than 0.05). This validates the importance to integrate tissue-specific molecular networks for studying disease gene prioritization and show the superiority of our network models and ranking algorithms toward this purpose. The source code and datasets are available at http://nijingchao.github.io/CRstar/ .

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

PubMed Central

Loughman, James; Wildsoet, Christine F.; Williams, Cathy; Guggenheim, Jeremy A.

2018-01-01

Purpose To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors. Methods Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests. Results Pathway analysis identified several biological processes already implicated in refractive error development through prior GWAS analyses and animal studies, including extracellular matrix remodeling, focal adhesion, and axon guidance, supporting the research hypothesis. Novel pathways also implicated in myopia development included mannosylation, glycosylation, lens development, gliogenesis, and Schwann cell differentiation. Hyperopia was found to be linked to a different pattern of biological processes, mostly related to organogenesis. Comparison with GWAS findings further confirmed that syndromic myopia genes were enriched for genetic variants that influence refractive errors in the general population. Gene-based analyses implicated 21 novel candidate myopia genes (ADAMTS18, ADAMTS2, ADAMTSL4, AGK, ALDH18A1, ASXL1, COL4A1, COL9A2, ERBB3, FBN1, GJA1, GNPTG, IFIH1, KIF11, LTBP2, OCA2, POLR3B, POMT1, PTPN11, TFAP2A, ZNF469). Conclusions Common genetic variants within or nearby genes that cause syndromic myopia are enriched for variants that cause nonsyndromic, common myopia. Analysis of syndromic forms of refractive errors can provide new insights into the etiology of myopia and additional potential targets for therapeutic interventions. PMID:29346494

Effect of Congenital Heart Defects on Language Development in Toddlers with Down Syndrome

ERIC Educational Resources Information Center

Visootsak, J.; Hess, B.; Bakeman, R.; Adamson, L. B.

2013-01-01

Background: Down syndrome (DS, OMIM #190685) is the most commonly identified genetic form of intellectual disability with congenital heart defect (CHD) occurring in 50% of cases. With advances in surgical techniques and an increasing lifespan, this has necessitated a greater understanding of the neurodevelopmental consequences of CHDs. Herein, we…

Expanding the phenotype of alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome): description of an additional case and review of the literature.

PubMed

Schell-Apacik, Chayim; Hardt, Michael; Ertl-Wagner, Birgit; Klopocki, Eva; Möhrenschlager, Matthias; Heinrich, Uwe; von Voss, Hubertus

2008-09-01

Alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome; OMIM 203550) is a very rare genetic disorder with distinct features. To our knowledge, there have been four cases documented to date. In addition, another three patients, previously described as having IFAP syndrome (OMIM %308205), may also have ACD syndrome. We report on one patient with short stature, total alopecia, ichthyosis, photophobia, seizures, ectrodactyly, vertebral anomalies, scoliosis, multiple contractures, mental retardation, and striking facial and other features (e.g. microdolichocephaly, missing eyebrows and eyelashes, long nose, large ears) consistent with ACD syndrome. Results of laboratory testing in the literature case reports were normal, although in none of them, array-CGH (microarray-based comparative genomic hybridization) analysis was performed. In conclusion, the combination of specific features, including total alopecia, ichthyosis, mental retardation, and skeletal anomalies are suggestive of ACD syndrome. We propose that children with this syndrome undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investigation, psychological testing, management of dermatologic and orthopedic problems, and genetic counseling.

Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis.

PubMed

Shears, D J; Vassal, H J; Goodman, F R; Palmer, R W; Reardon, W; Superti-Furga, A; Scambler, P J; Winter, R M

1998-05-01

Leri-Weill Dyschondrosteosis (LWD; OMIM 127300) is a dominantly inherited skeletal dysplasia characterized by disproportionate short stature with predominantly mesomelic limb shortening. Expression is variable and consistently more severe in females, who frequently display the Madelung deformity of the forearm (shortening and bowing of the radius with dorsal subluxation of the distal ulna). The rare Langer Mesomelic Dysplasia (LD; OMIM 249700), characterized by severe short stature with hypoplasia/aplasia of the ulna and fibula, has been postulated to be the homozygous form of LWD (refs 4-6). In a six-generation pedigree with LWD, we established linkage to the marker DXYS6814 in the pseudoautosomal region (PAR1) of the X and Y chromosomes (Z max=6.28; theta=0). Linkage analysis of three smaller pedigrees increased the lod score to 8.68 (theta=0). We identified submicroscopic PAR1 deletions encompassing the recently described short stature homeobox-containing gene SHOX (refs 7,8) segregating with the LWD phenotype in 5 families. A point mutation leading to a premature stop in exon 4 of SHOX was identified in one LWD family.

15 CFR Supplement No. 8 to Part 742 - Self-Classification Report for Encryption Items

Code of Federal Regulations, 2011 CFR

2011-01-01

... forensics (v) Cryptographic accelerator (vi) Data backup and recovery (vii) Database (viii) Disk/drive... (MAN) (xxii) Modem (xxiii) Network convergence or infrastructure n.e.s. (xxiv) Network forensics (xxv...

15 CFR Supplement No. 8 to Part 742 - Self-Classification Report for Encryption Items

Code of Federal Regulations, 2014 CFR

2014-01-01

... forensics (v) Cryptographic accelerator (vi) Data backup and recovery (vii) Database (viii) Disk/drive... (MAN) (xxii) Modem (xxiii) Network convergence or infrastructure n.e.s. (xxiv) Network forensics (xxv...

15 CFR Supplement No. 8 to Part 742 - Self-Classification Report for Encryption Items

Code of Federal Regulations, 2013 CFR

2013-01-01

... forensics (v) Cryptographic accelerator (vi) Data backup and recovery (vii) Database (viii) Disk/drive... (MAN) (xxii) Modem (xxiii) Network convergence or infrastructure n.e.s. (xxiv) Network forensics (xxv...

15 CFR Supplement No. 8 to Part 742 - Self-Classification Report for Encryption Items

Code of Federal Regulations, 2012 CFR

2012-01-01

... forensics (v) Cryptographic accelerator (vi) Data backup and recovery (vii) Database (viii) Disk/drive... (MAN) (xxii) Modem (xxiii) Network convergence or infrastructure n.e.s. (xxiv) Network forensics (xxv...

Inferring Alcoholism SNPs and Regulatory Chemical Compounds Based on Ensemble Bayesian Network.

PubMed

Chen, Huan; Sun, Jiatong; Jiang, Hong; Wang, Xianyue; Wu, Lingxiang; Wu, Wei; Wang, Qh

2017-01-01

The disturbance of consciousness is one of the most common symptoms of those have alcoholism and may cause disability and mortality. Previous studies indicated that several single nucleotide polymorphisms (SNP) increase the susceptibility of alcoholism. In this study, we utilized the Ensemble Bayesian Network (EBN) method to identify causal SNPs of alcoholism based on the verified GAW14 data. We built a Bayesian network combining random process and greedy search by using Genetic Analysis Workshop 14 (GAW14) dataset to establish EBN of SNPs. Then we predicted the association between SNPs and alcoholism by determining Bayes' prior probability. Thirteen out of eighteen SNPs directly connected with alcoholism were found concordance with potential risk regions of alcoholism in OMIM database. As many SNPs were found contributing to alteration on gene expression, known as expression quantitative trait loci (eQTLs), we further sought to identify chemical compounds acting as regulators of alcoholism genes captured by causal SNPs. Chloroprene and valproic acid were identified as the expression regulators for genes C11orf66 and SALL3 which were captured by alcoholism SNPs, respectively. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic diabetes insipidus in two brothers.

PubMed

Schernthaner-Reiter, Marie Helene; Adams, David; Trivellin, Giampaolo; Ramnitz, Mary Scott; Raygada, Margarita; Golas, Gretchen; Faucz, Fabio R; Nilsson, Ola; Nella, Aikaterini A; Dileepan, Kavitha; Lodish, Maya; Lee, Paul; Tifft, Cynthia; Markello, Thomas; Gahl, William; Stratakis, Constantine A

2016-05-01

X-linked nephrogenic diabetes insipidus (NDI, OMIM#304800) is caused by mutations in the arginine vasopressin (AVP, OMIM*192340) receptor type 2 (AVPR2, OMIM*300538) gene. A 20-month-old boy and his 8-year-old brother presented with polyuria, polydipsia, and failure to thrive. Both boys demonstrated partial DDAVP (1-desamino-8-D AVP or desmopressin) responses; thus, NDI diagnosis was delayed. While routine sequencing of AVPR2 showed a potential splice site variant, it was not until exome sequencing confirmed the AVPR2 splice site variant and did not reveal any more likely candidates that the patients' diagnosis was made and proper treatment was instituted. Both patients were hemizygous for two AVPR2 variants predicted in silico to affect AVPR2 messenger RNA (mRNA) splicing. A minigene assay revealed that the novel AVPR2 c.276A>G mutation creates a novel splice acceptor site leading to 5' truncation of AVPR2 exon 2 in HEK293 human kidney cells. Both patients have been treated with high-dose DDAVP with a remarkable improvement of their symptoms and accelerated linear growth and weight gain. We present here a unique case of partial X-linked NDI due to an AVPR2 splice site mutation; patients with diabetes insipidus of unknown etiology may harbor splice site mutations that are initially underestimated in their pathogenicity on sequence analysis. • X-linked nephrogenic diabetes insipidus is caused by AVPR2 mutations, and disease severity can vary depending on the functional effect of the mutation. What is New: • We demonstrate here that a splice site mutation in AVPR2 leads to partial X-linked NDI in two brothers. • Treatment with high-dose DDAVP led to improvement of polyuria and polydipsia, weight gain, and growth.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. SUPPL-507

NASA Technical Reports Server (NTRS)

2000-01-01

This report lists: reports, articles and other documents recently announced in the NASA STI Database. Contents include the following: Life sciences (general), aerospace medicine, behavioral sciences, man/system technology and life support, and exobioligy.

Landslide hazard rating matrix and database : executive summary report.

DOT National Transportation Integrated Search

2008-01-01

Landslides or embankment slope failures on : highways occur for a variety of reasons, such as : excessive precipitation, flooding, deterioration of : soil strength over time, and adverse man-made : activities. The slope failures not only affect : roa...

Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review.

PubMed

Tan, Benjamin H L; Ross, James A; Kaasa, Stein; Skorpen, Frank; Fearon, Kenneth C H

2011-04-01

Cancer cachexia is a polygenic and complex syndrome. Genetic variations in regulation of the inflammatory response, muscle and fat metabolic pathways, and pathways in appetite regulation are likely to contribute to the susceptibility or resistance to developing cancer cachexia. A systematic search of Medline and EmBase databases, covering 1986-2008 was performed for potential candidate genes/genetic polymorphisms relating to cancer cachexia. Related genes were then identified using pathway functional analysis software. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Genes with variants which had functional or clinical associations with cachexia and replicated in at least one study were entered into pathway analysis software to reveal possible network associations between genes. A total of 184 polymorphisms with functional or clinical relevance to cancer cachexia were identified in 92 candidate genes. Of these, 42 polymorphisms (in 33 genes) were replicated in more than one study with 13 polymorphisms found to influence two or more hallmarks of cachexia (i.e. inflammation, loss of fat mass and/or lean mass and reduced survival). Thirty-three genes were found to be significantly interconnected in two major networks with four genes (ADIPOQ, IL6, NFKB1 and TLR4) interlinking both networks. Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides an initial framework to select genes/polymorphisms for further study in cancer cachexia, and to develop their potential as susceptibility biomarkers of developing cachexia.

Assembly and Initial Analysis of a Database of the Characteristics of Fixed-Wing Unmanned Aircraft Systems

DTIC Science & Technology

2014-11-01

sea level (evaluated for turbojet- and turbofan -powered UAVs and targets only) R range (km) ferryR ferry range (km) radiusR mission radius (km...operating airspeed for manned turbofan -powered aircraft, and a power law for birds derived by Alerstam et al. [22...UAVs in the Database; and ratio of operating to maximum airspeed for turbojet- or turbofan -powered UAVs with mmax > 103 kg

In silico analysis of β-mannanases and β-mannosidase from Aspergillus flavus and Trichoderma virens UKM1

NASA Astrophysics Data System (ADS)

Yee, Chai Sin; Murad, Abdul Munir Abdul; Bakar, Farah Diba Abu

2013-11-01

A gene encoding an endo-β-1,4-mannanase from Trichoderma virens UKM1 (manTV) and Aspergillus flavus UKM1 (manAF) was analysed with bioinformatic tools. In addition, A. flavus NRRL 3357 genome database was screened for a β-mannosidase gene and analysed (mndA-AF). These three genes were analysed to understand their gene properties. manTV and manAF both consists of 1,332-bp and 1,386-bp nucleotides encoding 443 and 461 amino acid residues, respectively. Both the endo-β-1,4-mannanases belong to the glycosyl hydrolase family 5 and contain a carbohydrate-binding module family 1 (CBM1). On the other hand, mndA-AF which is a 2,745-bp gene encodes a protein sequence of 914 amino acid residues. This β-mannosidase belongs to the glycosyl hydrolase family 2. Predicted molecular weight of manTV, manAF and mndA-AF are 47.74 kDa, 49.71 kDa and 103 kDa, respectively. All three predicted protein sequences possessed signal peptide sequence and are highly conserved among other fungal β-mannanases and β-mannosidases.

5S ribosomal RNA database Y2K

PubMed Central

Szymanski, Maciej; Barciszewska, Miroslawa Z.; Barciszewski, Jan; Erdmann, Volker A.

2000-01-01

This paper presents the updated version (Y2K) of the database of ribosomal 5S ribonucleic acids (5S rRNA) and their genes (5S rDNA), http://rose.man/poznan. pl/5SData/index.html . This edition of the database contains 1985 primary structures of 5S rRNA and 5S rDNA. They include 60 archaebacterial, 470 eubacterial, 63 plastid, nine mitochondrial and 1383 eukaryotic sequences. The nucleotide sequences of the 5S rRNAs or 5S rDNAs are divided according to the taxonomic position of the source organisms. PMID:10592212

5S ribosomal RNA database Y2K.

PubMed

Szymanski, M; Barciszewska, M Z; Barciszewski, J; Erdmann, V A

2000-01-01

This paper presents the updated version (Y2K) of the database of ribosomal 5S ribonucleic acids (5S rRNA) and their genes (5S rDNA), http://rose.man/poznan.pl/5SData/index.html. This edition of the database contains 1985primary structures of 5S rRNA and 5S rDNA. They include 60 archaebacterial, 470 eubacterial, 63 plastid, nine mitochondrial and 1383 eukaryotic sequences. The nucleotide sequences of the 5S rRNAs or 5S rDNAs are divided according to the taxonomic position of the source organisms.

The unexpected memorial.

PubMed

Holloway, Richard L

2018-03-01

In this article, the current author tells the story of an unexpected musical memorial he and his fellow band mates performed as a tribute to a man named Gordon "Gizmo," a husband and father. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A survey of disease connections for CD4+ T cell master genes and their directly linked genes.

PubMed

Li, Wentian; Espinal-Enríquez, Jesús; Simpfendorfer, Kim R; Hernández-Lemus, Enrique

2015-12-01

Genome-wide association studies and other genetic analyses have identified a large number of genes and variants implicating a variety of disease etiological mechanisms. It is imperative for the study of human diseases to put these genetic findings into a coherent functional context. Here we use system biology tools to examine disease connections of five master genes for CD4+ T cell subtypes (TBX21, GATA3, RORC, BCL6, and FOXP3). We compiled a list of genes functionally interacting (protein-protein interaction, or by acting in the same pathway) with the master genes, then we surveyed the disease connections, either by experimental evidence or by genetic association. Embryonic lethal genes (also known as essential genes) are over-represented in master genes and their interacting genes (55% versus 40% in other genes). Transcription factors are significantly enriched among genes interacting with the master genes (63% versus 10% in other genes). Predicted haploinsufficiency is a feature of most these genes. Disease-connected genes are enriched in this list of genes: 42% of these genes have a disease connection according to Online Mendelian Inheritance in Man (OMIM) (versus 23% in other genes), and 74% are associated with some diseases or phenotype in a Genome Wide Association Study (GWAS) (versus 43% in other genes). Seemingly, not all of the diseases connected to genes surveyed were immune related, which may indicate pleiotropic functions of the master regulator genes and associated genes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Selection of optimum ionic liquid solvents for flavonoid and phenolic acids extraction

NASA Astrophysics Data System (ADS)

Rahman, N. R. A.; Yunus, N. A.; Mustaffa, A. A.

2017-06-01

Phytochemicals are important in improving human health with their functions as antioxidants, antimicrobials and anticancer agents. However, the quality of phytochemicals extract relies on the efficiency of extraction process. Ionic liquids (ILs) have become a research phenomenal as extraction solvent due to their unique properties such as unlimited range of ILs, non-volatile, strongly solvating and may become either polarity. In phytochemical extraction, the determination of the best solvent that can extract highest yield of solute (phytochemical) is very important. Therefore, this study is conducted to determine the best IL solvent to extract flavonoids and phenolic acids through a property prediction modeling approach. ILs were selected from the imidazolium-based anion for alkyl chains ranging from ethyl > octyl and cations consisting of Br, Cl, [PF6], BF4], [H2PO4], [SO4], [CF3SO3], [TF2N] and [HSO4]. This work are divided into several stages. In Stage 1, a Microsoft Excel-based database containing available solubility parameter values of phytochemicals and ILs including its prediction models and their parameters has been established. The database also includes available solubility data of phytochemicals in IL, and activity coefficient models, for solid-liquid phase equilibrium (SLE) calculations. In Stage 2, the solubility parameter values of the flavonoids (e.g. kaempferol, quercetin and myricetin) and phenolic acids (e.g. gallic acid and caffeic acid) are determined either directly from database or predicted using Stefanis and Marrero-Gani group contribution model for the phytochemicals. A cation-anion contribution model is used for IL. In Stage 3, the amount of phytochemicals extracted can be determined by using SLE relationship involving UNIFAC-IL model. For missing parameters (UNIFAC-IL), they are regressed using available solubility data. Finally, in Stage 4, the solvent candidates are ranked and five ILs, ([OMIM] [TF2N], [HeMIM] [TF2N], [HMIM] [TF2N], [HeMIM] [CF3SO3] and [HMIM] [CF3SO3]) were identified and selected.

Setting the scene for SWOT: global maps of river reach hydrodynamic variables

NASA Astrophysics Data System (ADS)

Schumann, Guy J.-P.; Durand, Michael; Pavelsky, Tamlin; Lion, Christine; Allen, George

2017-04-01

Credible and reliable characterization of discharge from the Surface Water and Ocean Topography (SWOT) mission using the Manning-based algorithms needs a prior estimate constraining reach-scale channel roughness, base flow and river bathymetry. For some places, any one of those variables may exist locally or even regionally as a measurement, which is often only at a station, or sometimes as a basin-wide model estimate. However, to date none of those exist at the scale required for SWOT and thus need to be mapped at a continental scale. The prior estimates will be employed for producing initial discharge estimates, which will be used as starting-guesses for the various Manning-based algorithms, to be refined using the SWOT measurements themselves. A multitude of reach-scale variables were derived, including Landsat-based width, SRTM slope and accumulation area. As a possible starting point for building the prior database of low flow, river bathymetry and channel roughness estimates, we employed a variety of sources, including data from all GRDC records, simulations from the long-time runs of the global water balance model (WBM), and reach-based calculations from hydraulic geometry relationships as well as Manning's equation. Here, we present the first global maps of this prior database with some initial validation, caveats and prospective uses.

Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein-Taybi and Filippi syndromes.

PubMed

de Vries, Tamar I; Monroe, Glen R; van Belzen, Martine J; van der Lans, Christian A; Savelberg, Sanne Mc; Newman, William G; van Haaften, Gijs; Nievelstein, Rutger A; van Haelst, Mieke M

2016-08-01

Rubinstein-Taybi syndrome (RTS, OMIM 180849) and Filippi syndrome (FLPIS, OMIM 272440) are both rare syndromes, with multiple congenital anomalies and intellectual deficit (MCA/ID). We present a patient with intellectual deficit, short stature, bilateral syndactyly of hands and feet, broad thumbs, ocular abnormalities, and dysmorphic facial features. These clinical features suggest both RTS and FLPIS. Initial DNA analysis of DNA isolated from blood did not identify variants to confirm either of these syndrome diagnoses. Whole-exome sequencing identified a homozygous variant in C9orf173, which was novel at the time of analysis. Further Sanger sequencing analysis of FLPIS cases tested negative for CKAP2L variants did not, however, reveal any further variants. Subsequent analysis using DNA isolated from buccal mucosa revealed a mosaic variant in CREBBP. This report highlights the importance of excluding mosaic variants in patients with a strong but atypical clinical presentation of a MCA/ID syndrome if no disease-causing variants can be detected in DNA isolated from blood samples. As the striking syndactyly observed in the present case is typical for FLPIS, we suggest CREBBP analysis in saliva samples for FLPIS syndrome cases in which no causal CKAP2L variant is detected.

Health Assessment Document for Chromium (Final Report, 1983)

EPA Science Inventory

This final report summarizes a comprehensive database that considers all sources of chromium in the environment, the likelihood for its exposure to humans, and the possible consequences to man and lower organisms from its absorption. This information is integrated into a format t...

The first successful use of a low stringency familial match in a French criminal investigation.

PubMed

Pham-Hoai, Emmanuel; Crispino, Frank; Hampikian, Greg

2014-05-01

We describe how a very simple application of familial searching resolved a decade-old, high-profile rape/murder in France. This was the first use of familial searching in a criminal case using the French STR DNA database, which contains approximately 1,800,000 profiles. When an unknown forensic profile (18 loci) was searched against the French arrestee/offender database using CODIS configured for a low stringency search, a single low stringency match was identified. This profile was attributed to the father of the man suspected to be the source of the semen recovered from the murder victim Elodie Kulik. The identification was confirmed using Y-chromosome DNA from the putative father, an STR profile from the mother, and finally a tissue sample from the exhumed body of the man who left the semen. Because of this identification, the investigators are now pursuing possible co-conspirators. © 2014 American Academy of Forensic Sciences.

EV@LUTIL: An open access database on occupational exposures to asbestos and man-made mineral fibres.

PubMed

Orlowski, Ewa; Audignon-Durand, Sabyne; Goldberg, Marcel; Imbernon, Ellen; Brochard, Patrick

2015-10-01

The aim of Evalutil is to document occupational exposure to asbestos and man-made mineral fibers. These databases provide grouped descriptive and metrological data from observed situations of occupational exposure, collected through the analysis of scientific articles and technical reports by industrial hygienists. Over 5,000 measurements were collected. We describe the occupations, economic activities, fiber-containing products, and operations on them that have been documented most often. Graphical measurement syntheses of these data show that the situations presented for asbestos and RCF, except mineral wools, report fiber concentrations mainly above historical occupational exposure limits. Free access to these data in French and in English on the Internet (https://ssl2.isped.u-bordeaux2.fr/eva_003/) helps public health and prevention professionals to identify and characterize occupational exposures to fibers. Extended recently to nanoscale particles, Evalutil continues to contribute to the improvement of knowledge about exposure to inhaled particles and the health risks associated with them. © 2015 Wiley Periodicals, Inc.

Novel High-Fidelity Screening of Environmental Chemicals and Carcinogens and Mechanisms in Colorectal Cancer.

DTIC Science & Technology

2016-09-01

Chemical Promiscuity, Pharmacokinetics, Colorectal Cancer, N , N ’-disalicylidene-1,2-diaminopropane, Pyraclostrobin, Paclobutrazol, Vitamin D Receptor, Wnt...Environmental Chemicals, TOX-TMFS, CPTM, Cancer Cellular Network Model, Chemical Reactivity, Chemical Promiscuity, Pharmacokinetics, Colorectal Cancer, N , N ...network models were further enriched with oncologic disease OMIM profiles to create cancer-specific networks. The ECs N , N ’-disalicylidene- 1,2

Mapping proteins to disease terminologies: from UniProt to MeSH

PubMed Central

Mottaz, Anaïs; Yip, Yum L; Ruch, Patrick; Veuthey, Anne-Lise

2008-01-01

Background Although the UniProt KnowledgeBase is not a medical-oriented database, it contains information on more than 2,000 human proteins involved in pathologies. However, these annotations are not standardized, which impairs the interoperability between biological and clinical resources. In order to make these data easily accessible to clinical researchers, we have developed a procedure to link diseases described in the UniProtKB/Swiss-Prot entries to the MeSH disease terminology. Results We mapped disease names extracted either from the UniProtKB/Swiss-Prot entry comment lines or from the corresponding OMIM entry to the MeSH. Different methods were assessed on a benchmark set of 200 disease names manually mapped to MeSH terms. The performance of the retained procedure in term of precision and recall was 86% and 64% respectively. Using the same procedure, more than 3,000 disease names in Swiss-Prot were mapped to MeSH with comparable efficiency. Conclusions This study is a first attempt to link proteins in UniProtKB to the medical resources. The indexing we provided will help clinicians and researchers navigate from diseases to genes and from genes to diseases in an efficient way. The mapping is available at: . PMID:18460185

[Review of digital ground object spectral library].

PubMed

Zhou, Xiao-Hu; Zhou, Ding-Wu

2009-06-01

A higher spectral resolution is the main direction of developing remote sensing technology, and it is quite important to set up the digital ground object reflectance spectral database library, one of fundamental research fields in remote sensing application. Remote sensing application has been increasingly relying on ground object spectral characteristics, and quantitative analysis has been developed to a new stage. The present article summarized and systematically introduced the research status quo and development trend of digital ground object reflectance spectral libraries at home and in the world in recent years. Introducing the spectral libraries has been established, including desertification spectral database library, plants spectral database library, geological spectral database library, soil spectral database library, minerals spectral database library, cloud spectral database library, snow spectral database library, the atmosphere spectral database library, rocks spectral database library, water spectral database library, meteorites spectral database library, moon rock spectral database library, and man-made materials spectral database library, mixture spectral database library, volatile compounds spectral database library, and liquids spectral database library. In the process of establishing spectral database libraries, there have been some problems, such as the lack of uniform national spectral database standard and uniform standards for the ground object features as well as the comparability between different databases. In addition, data sharing mechanism can not be carried out, etc. This article also put forward some suggestions on those problems.

Database extraction strategies for low-template evidence.

PubMed

Bleka, Øyvind; Dørum, Guro; Haned, Hinda; Gill, Peter

2014-03-01

Often in forensic cases, the profile of at least one of the contributors to a DNA evidence sample is unknown and a database search is needed to discover possible perpetrators. In this article we consider two types of search strategies to extract suspects from a database using methods based on probability arguments. The performance of the proposed match scores is demonstrated by carrying out a study of each match score relative to the level of allele drop-out in the crime sample, simulating low-template DNA. The efficiency was measured by random man simulation and we compared the performance using the SGM Plus kit and the ESX 17 kit for the Norwegian population, demonstrating that the latter has greatly enhanced power to discover perpetrators of crime in large national DNA databases. The code for the database extraction strategies will be prepared for release in the R-package forensim. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 385)

NASA Technical Reports Server (NTRS)

1994-01-01

This bibliography lists 536 reports, articles and other documents introduced into the NASA Scientific and Technical Information System Database. Subject coverage includes: aerospace medicine and physiology, life support systems and man/system technology, protective clothing, exobiology and extraterrestrial life, planetary biology, and flight crew behavior and performance.

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 388)

NASA Technical Reports Server (NTRS)

1994-01-01

This bibliography lists 132 reports, articles and other documents introduced into the NASA Scientific and Technical Information Database. Subject coverage includes: aerospace medicine and physiology, life support systems and man/system technology, protective clothing, exobiology and extraterrestrial life, planetary biology, and flight crew behavior and performance.

Knowledge Discovery and Data Mining in Iran's Climatic Researches

NASA Astrophysics Data System (ADS)

Karimi, Mostafa

2013-04-01

Advances in measurement technology and data collection is the database gets larger. Large databases require powerful tools for analysis data. Iterative process of acquiring knowledge from information obtained from data processing is done in various forms in all scientific fields. However, when the data volume large, and many of the problems the Traditional methods cannot respond. in the recent years, use of databases in various scientific fields, especially atmospheric databases in climatology expanded. in addition, increases in the amount of data generated by the climate models is a challenge for analysis of it for extraction of hidden pattern and knowledge. The approach to this problem has been made in recent years uses the process of knowledge discovery and data mining techniques with the use of the concepts of machine learning, artificial intelligence and expert (professional) systems is overall performance. Data manning is analytically process for manning in massive volume data. The ultimate goal of data mining is access to information and finally knowledge. climatology is a part of science that uses variety and massive volume data. Goal of the climate data manning is Achieve to information from variety and massive atmospheric and non-atmospheric data. in fact, Knowledge Discovery performs these activities in a logical and predetermined and almost automatic process. The goal of this research is study of uses knowledge Discovery and data mining technique in Iranian climate research. For Achieve This goal, study content (descriptive) analysis and classify base method and issue. The result shown that in climatic research of Iran most clustering, k-means and wards applied and in terms of issues precipitation and atmospheric circulation patterns most introduced. Although several studies in geography and climate issues with statistical techniques such as clustering and pattern extraction is done, Due to the nature of statistics and data mining, but cannot say for internal climate studies in data mining and knowledge discovery techniques are used. However, it is necessary to use the KDD Approach and DM techniques in the climatic studies, specific interpreter of climate modeling result.

[Triplet expansion cytosine-guanine-guanine: Three cases of OMIM syndrome in the same family].

PubMed

González-Pérez, Jesús; Izquierdo-Álvarez, Silvia; Fuertes-Rodrigo, Cristina; Monge-Galindo, Lorena; Peña-Segura, José Luis; López-Pisón, Francisco Javier

2016-04-01

The dynamic increase in the number of triplet repeats of cytosine-guanine-guanine (CGG) in the FMR1 gene mutation is responsible for three OMIM syndromes with a distinct clinical phenotype: Fragile X syndrome (FXS) and two pathologies in adult carriers of the premutation (55-200 CGG repeats): Primary ovarian insufficiency (FXPOI) and tremor-ataxia syndrome (FXTAS) associated with FXS. CGG mutation dynamics of the FMR1 gene were studied in DNA samples from peripheral blood from the index case and other relatives of first, second and third degree by TP-PCR, and the percentage methylation. Diagnosis of FXS was confirmed in three patients (21.4%), eight patients (57.1%) were confirmed in the premutation range transmitters, one male patient with full mutation/permutation mosaicism (7.1%) and two patients (14.3%) with normal study. Of the eight permutated patients, three had FXPOI and one male patient had FXTAS. Our study suggests the importance of making an early diagnosis of SXF in order to carry out a family study and genetic counselling, which allow the identification of new cases or premutated patients with FMR1 gene- associated syndromes (FXTAS, FXPOI). Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

HMG CoA lyase deficiency: identification of five causal point mutations in codons 41 and 42, including a frequent Saudi Arabian mutation, R41Q.

PubMed Central

Mitchell, G A; Ozand, P T; Robert, M F; Ashmarina, L; Roberts, J; Gibson, K M; Wanders, R J; Wang, S; Chevalier, I; Plöchl, E; Miziorko, H

1998-01-01

The hereditary deficiency of 3-hydroxy-3-methylglutaryl (HMG) CoA lyase (HL; OMIM 246450 [http://www3.ncbi.nlm.nih. gov:80/htbin-post/Omim/dispmim?246450]) results in episodes of hypoketotic hypoglycemia and coma and is reported to be frequent and clinically severe in Saudi Arabia. We found genetic diversity among nine Saudi HL-deficient probands: six were homozygous for the missense mutation R41Q, and two were homozygous for the frameshift mutation F305fs(-2). In 32 non-Saudi HL-deficient probands, we found three R41Q alleles and also discovered four other deleterious point mutations in codons 41 and 42: R41X, D42E, D42G, and D42H. In purified mutant recombinant HL, all four missense mutations in codons 41 and 42 cause a marked decrease in HL activity. We developed a screening procedure for HL missense mutations that yields residual activity at levels comparable to those obtained using purified HL peptides. Codons 41 and 42 are important for normal HL catalysis and account for a disproportionate 21 (26%) of 82 of mutant alleles in our group of HL-deficient probands. PMID:9463337

Peeling skin syndrome in eight cases of four different families from India and Bangladesh.

PubMed

Sarma, Nilendu; Boler, Anup Kumar; Bhanja, Dulal Chandra

2012-01-01

Peeling skin syndrome (PSS) is a rare recessively inherited ichthyosiform genodermatoses characterized by superficial skin peeling. This has 2 subtypes, acral (APSS; OMIM 609796) and generalized form (OMIM 270300). The later has been subdivided into type A (non-inflammatory) and type B (inflammatory). Eight cases of peeling skin syndrome in 4 families were recorded over a period of 5 years. They were diagnosed clinically and confirmed histopathologically. Disease onset ranged from birth to childhood age (mean 5.25 ± 4.528 years) and age at presentation ranged from 7-35 years (mean 23.25 ± 10.471 years). Males outnumbered females (M:F - 5:3). All had non-inflammatory generalized disease of type-A PSS variety, except one who had type-B PSS. Two Muslim families (1 st and 2 nd family, total 5 patients) came from nearby country Bangladesh, and the 2 Hindu families were Indian. Higher severity over acral areas in generalized type, possible autosomal dominant pattern of inheritance and improvement with age as found in this series were new manifestations and possibly unreported previously. The disease was found to be poorly responsive to oral retinoids. Prevalence of the disease may be higher than expected. Importance of mutational analysis was also highlighted.

Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein–Taybi and Filippi syndromes

PubMed Central

de Vries, Tamar I; R Monroe, Glen; van Belzen, Martine J; van der Lans, Christian A; Savelberg, Sanne MC; Newman, William G; van Haaften, Gijs; Nievelstein, Rutger A; van Haelst, Mieke M

2016-01-01

Rubinstein–Taybi syndrome (RTS, OMIM 180849) and Filippi syndrome (FLPIS, OMIM 272440) are both rare syndromes, with multiple congenital anomalies and intellectual deficit (MCA/ID). We present a patient with intellectual deficit, short stature, bilateral syndactyly of hands and feet, broad thumbs, ocular abnormalities, and dysmorphic facial features. These clinical features suggest both RTS and FLPIS. Initial DNA analysis of DNA isolated from blood did not identify variants to confirm either of these syndrome diagnoses. Whole-exome sequencing identified a homozygous variant in C9orf173, which was novel at the time of analysis. Further Sanger sequencing analysis of FLPIS cases tested negative for CKAP2L variants did not, however, reveal any further variants. Subsequent analysis using DNA isolated from buccal mucosa revealed a mosaic variant in CREBBP. This report highlights the importance of excluding mosaic variants in patients with a strong but atypical clinical presentation of a MCA/ID syndrome if no disease-causing variants can be detected in DNA isolated from blood samples. As the striking syndactyly observed in the present case is typical for FLPIS, we suggest CREBBP analysis in saliva samples for FLPIS syndrome cases in which no causal CKAP2L variant is detected. PMID:26956253

A meta-analysis of manual versus remote magnetic navigation for ventricular tachycardia ablation.

PubMed

Turagam, Mohit K; Atkins, Donita; Tung, Roderick; Mansour, Moussa; Ruskin, Jeremy; Cheng, Jie; Di Biase, Luigi; Natale, Andrea; Lakkireddy, Dhanunjaya

2017-09-01

There are limited studies on the safety and efficacy of remote magnetic navigation (RMN) versus manual navigation (MAN) in ventricular tachycardia (VT) ablation. A comprehensive literature search was performed using the keywords VT ablation, stereotaxis, RMN and MAN in Pubmed, Ebsco, Web of Science, Cochrane, and Google scholar databases. The analysis included seven studies (one randomized, three prospective observational, and three retrospective) including 779 patients [both structural heart disease (SHD) and idiopathic VT] comparing RMN (N = 433) and MAN (N = 339) in VT ablation. The primary end point of long-term VT recurrence was significantly lower with RMN (OR 0.61, 95% CI 0.44-0.85, p = 0.003) compared with MAN. Other end points of acute procedural success (OR 2.13, 95% CI 1.40-3.23, p = 0.0004) was significantly higher with RMN compared with MAN. Fluoroscopy [mean difference -10.42, 95% CI -12.7 to -8.1, p < 0.0001], procedural time [mean difference -9.79, 95% CI -19.27 to -0.3, p = 0.04] and complications (OR 0.35, 95% CI 0.17-0.74, p = 0.0006) were also significantly lower in RMN when compared with MAN. In a subgroup analysis SHD, there was no significant difference in VT recurrence or acute procedural success with RMN vs. MAN. In idiopathic VT, RMN significantly increased acute procedural success with no difference in VT recurrence. The results demonstrate that RMN is safe and effective when compared with MAN in patients with both SHD and idiopathic VT undergoing catheter ablation. Further prospective studies are needed to further verify the safety and efficacy of RMN.

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 375)

NASA Technical Reports Server (NTRS)

1993-01-01

This bibliography lists 212 reports, articles, and other documents recently introduced into the NASA Scientific and Technical Information System database. Subject coverage includes the following: aerospace medicine and physiology, life support systems and man/system technology, protective clothing, exobiology and extraterrestrial life, planetary biology, and flight crew behavior and performance.

Research on keyword retrieval method of HBase database based on index structure

NASA Astrophysics Data System (ADS)

Gong, Pijin; Lv, Congmin; Gong, Yongsheng; Ma, Haozhi; Sun, Yang; Wang, Lu

2017-10-01

With the rapid development of manned spaceflight engineering, the scientific experimental data in space application system is increasing rapidly. How to efficiently query the specific data in the mass data volume has become a problem. In this paper, a method of retrieving the object data based on the object attribute as the keyword is proposed. The HBase database is used to store the object data and object attributes, and the secondary index is constructed. The research shows that this method is a good way to retrieve specified data based on object attributes.

ALARA database value in future outage work planning and dose management

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, D.W.; Green, W.H.

1995-03-01

ALARA database encompassing job-specific duration and man-rem plant specific information over three refueling outages represents an invaluable tool for the outage work planner and ALARA engineer. This paper describes dose-management trends emerging based on analysis of three refueling outages at Clinton Power Station. Conclusions reached based on hard data available from a relational database dose-tracking system is a valuable tool for planning of future outage work. The system`s ability to identify key problem areas during a refueling outage is improving as more outage comparative data becomes available. Trends over a three outage period are identified in this paper in themore » categories of number and type of radiation work permits implemented, duration of jobs, projected vs. actual dose rates in work areas, and accuracy of outage person-rem projection. The value of the database in projecting 1 and 5 year station person-rem estimates is discussed.« less

Database resources of the National Center for Biotechnology Information

PubMed Central

Wheeler, David L.; Barrett, Tanya; Benson, Dennis A.; Bryant, Stephen H.; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M.; DiCuccio, Michael; Edgar, Ron; Federhen, Scott; Geer, Lewis Y.; Helmberg, Wolfgang; Kapustin, Yuri; Kenton, David L.; Khovayko, Oleg; Lipman, David J.; Madden, Thomas L.; Maglott, Donna R.; Ostell, James; Pruitt, Kim D.; Schuler, Gregory D.; Schriml, Lynn M.; Sequeira, Edwin; Sherry, Stephen T.; Sirotkin, Karl; Souvorov, Alexandre; Starchenko, Grigory; Suzek, Tugba O.; Tatusov, Roman; Tatusova, Tatiana A.; Wagner, Lukas; Yaschenko, Eugene

2006-01-01

In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups, Retroviral Genotyping Tools, HIV-1, Human Protein Interaction Database, SAGEmap, Gene Expression Omnibus, Entrez Probe, GENSAT, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of the resources can be accessed through the NCBI home page at: . PMID:16381840

eRAM: encyclopedia of rare disease annotations for precision medicine.

PubMed

Jia, Jinmeng; An, Zhongxin; Ming, Yue; Guo, Yongli; Li, Wei; Liang, Yunxiang; Guo, Dongming; Li, Xin; Tai, Jun; Chen, Geng; Jin, Yaqiong; Liu, Zhimei; Ni, Xin; Shi, Tieliu

2018-01-04

Rare diseases affect over a hundred million people worldwide, most of these patients are not accurately diagnosed and effectively treated. The limited knowledge of rare diseases forms the biggest obstacle for improving their treatment. Detailed clinical phenotyping is considered as a keystone of deciphering genes and realizing the precision medicine for rare diseases. Here, we preset a standardized system for various types of rare diseases, called encyclopedia of Rare disease Annotations for Precision Medicine (eRAM). eRAM was built by text-mining nearly 10 million scientific publications and electronic medical records, and integrating various data in existing recognized databases (such as Unified Medical Language System (UMLS), Human Phenotype Ontology, Orphanet, OMIM, GWAS). eRAM systematically incorporates currently available data on clinical manifestations and molecular mechanisms of rare diseases and uncovers many novel associations among diseases. eRAM provides enriched annotations for 15 942 rare diseases, yielding 6147 human disease related phenotype terms, 31 661 mammalians phenotype terms, 10,202 symptoms from UMLS, 18 815 genes and 92 580 genotypes. eRAM can not only provide information about rare disease mechanism but also facilitate clinicians to make accurate diagnostic and therapeutic decisions towards rare diseases. eRAM can be freely accessed at http://www.unimd.org/eram/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

A novel NF1 mutation in a Chinese patient with giant café-au-lait macule in neurofibromatosis type 1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

PubMed

Tong, H-X; Li, M; Zhang, Y; Zhu, J; Lu, W-Q

2012-08-29

Neurofibromatosis type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder that is characterized by multiple café-au-lait, skinfold freckling, Lisch nodules, and neurofibromas. Mutations in the NF1 gene, which encodes the neurofibromin protein, have been identified as the pathogenic gene of NF1. In this study, we present a clinical and molecular study of a Chinese patient with giant café-au-lait in NF1. The patient showed >6 café-au-lait spots on the body, axillary freckling, and multiple subcutaneous neurofibromas. He also had a malignant peripheral nerve sheath tumor and bone abnormalities. The germline mutational analysis of the NF1 gene revealed a novel missense mutation in exon 13. It is a novel heterozygous nucleotide G>A transition at position 2241 of the NF1 gene. We found no mutation in malignant peripheral nerve sheath tumor DNA from this patient. This expands the database for NF1 gene mutations in NF1. Its absence in the normal chromosomes suggests that it is responsible for the NF1 phenotype. To our knowledge, this is the first case of giant café-au-lait macule in NF1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

Cortical Thought Theory: A Working Model of the Human Gestalt Mechanism.

DTIC Science & Technology

1985-07-01

time is proportional to KA , where K is some number and N is the number of pertinent pieces of information in the database (or size of ; the input...Functions In Man. Basic Books: New York, 1966. 77. Maffei, Lamberto, and Adriana Fiorentini. "The Visual Cortex As A Spatial Frequency Analyser." Vision

Magnetic solid phase extraction using ionic liquid-coated core-shell magnetic nanoparticles followed by high-performance liquid chromatography for determination of Rhodamine B in food samples.

PubMed

Chen, Jieping; Zhu, Xiashi

2016-06-01

Three hydrophobic ionic liquids (ILs) (1-butyl-3-methylimidazole hexafluorophosphate ([BMIM]PF6), 1-hexyl-3-methyl-imidazole hexafluoro-phosphate ([HMIM]PF6), and 1-octyl-3-methylimidazole hexafluorophosphate ([OMIM]PF6)) were used to coat Fe3O4@SiO2 nanoparticles (NPs) with core-shell structures to prepare magnetic solid phase extraction (MSPE) agents (Fe3O4@SiO2@IL). A novel method of MSPE coupled with high-performance liquid chromatography for the separation/analysis of Rhodamine B was then established. The results showed that Rhodamine B was adsorbed rapidly on Fe3O4@SiO2@[OMIM]PF6 and was released using ethanol. Under optimal conditions, the pre-concentration factor for the proposed method was 25. The linear range, limit of detection (LOD), correlation coefficient (R), and relative standard deviation (RSD) were found to be 0.50-150.00 μgL(-1), 0.08 μgL(-1), 0.9999, and 0.51% (n=3, c=10.00 μgL(-1)), respectively. The Fe3O4@SiO2 NPs could be re-used up to 10 times. The method was successfully applied to the determination of Rhodamine B in food samples. Copyright © 2016. Published by Elsevier Ltd.

Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.

PubMed

Parvari, Ruti; Hershkovitz, Eli; Grossman, Nili; Gorodischer, Rafael; Loeys, Bart; Zecic, Alexandra; Mortier, Geert; Gregory, Simon; Sharony, Reuven; Kambouris, Marios; Sakati, Nadia; Meyer, Brian F; Al Aqeel, Aida I; Al Humaidan, Abdul Karim; Al Zanhrani, Fatma; Al Swaid, Abdulrahman; Al Othman, Johara; Diaz, George A; Weiner, Rory; Khan, K Tahseen S; Gordon, Ronald; Gelb, Bruce D

2002-11-01

The syndrome of congenital hypoparathyroidism, mental retardation, facial dysmorphism and extreme growth failure (HRD or Sanjad-Sakati syndrome; OMIM 241410) is an autosomal recessive disorder reported almost exclusively in Middle Eastern populations. A similar syndrome with the additional features of osteosclerosis and recurrent bacterial infections has been classified as autosomal recessive Kenny-Caffey syndrome (AR-KCS; OMIM 244460). Both traits have previously been mapped to chromosome 1q43-44 (refs 5,6) and, despite the observed clinical variability, share an ancestral haplotype, suggesting a common founder mutation. We describe refinement of the critical region to an interval of roughly 230 kb and identification of deletion and truncation mutations of TBCE in affected individuals. The gene TBCE encodes one of several chaperone proteins required for the proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers. Analysis of diseased fibroblasts and lymphoblastoid cells showed lower microtubule density at the microtubule-organizing center (MTOC) and perturbed microtubule polarity in diseased cells. Immunofluorescence and ultrastructural studies showed disturbances in subcellular organelles that require microtubules for membrane trafficking, such as the Golgi and late endosomal compartments. These findings demonstrate that HRD and AR-KCS are chaperone diseases caused by a genetic defect in the tubulin assembly pathway, and establish a potential connection between tubulin physiology and the development of the parathyroid.

The SHOX region and its mutations.

PubMed

Capone, L; Iughetti, L; Sabatini, S; Bacciaglia, A; Forabosco, A

2010-06-01

The short stature homeobox-containing (SHOX) gene lies in the pseudoautosomal region 1 (PAR1) that comprises 2.6 Mb of the short-arm tips of both the X and Y chromosomes. It is known that its heterozygous mutations cause Leri-Weill dyschondrosteosis (LWD) (OMIM #127300), while its homozygous mutations cause a severe form of dwarfism known as Langer mesomelic dysplasia (LMD) (OMIM #249700). The analysis of 238 LWD patients between 1998 and 2007 by multiple authors shows a prevalence of deletions (46.4%) compared to point mutations (21.2%). On the whole, deletions and point mutations account for about 67% of LWD patients. SHOX is located within a 1000 kb desert region without genes. The comparative genomic analysis of this region between genomes of different vertebrates has led to the identification of evolutionarily conserved non-coding DNA elements (CNE). Further functional studies have shown that one of these CNE downstream of the SHOX gene is necessary for the expression of SHOX; this is considered to be typical "enhancer" activity. Including the enhancer, the overall mutation of the SHOX region in LWD patients does not hold in 100% of cases. Various authors have demonstrated the existence of other CNE both downstream and upstream of SHOX regions. The resulting conclusion is that it is necessary to reanalyze all LWD/LMD patients without SHOX mutations for the presence of mutations in the 5'- and 3'-flanking SHOX regions.

A genetic locus for sensory epilepsy precipitated by contact with hot water maps to chromosome 9p24.3-p23.

PubMed

Karan, Kalpita R; Satishchandra, Parthasarthy; Sinha, Sanjib; Anand, Anuranjan

2018-06-01

Hot water epilepsy (HWE) is a rare form of sensory epilepsy where seizures are precipitated by a stimulus of contact with hot water. While earlier studies have suggested causal role of genes for HWE, specific underpinnings are beginning to be explored only recently. We carried out a whole genome-based linkage analysis in a family where most of its members affected by HWE and found evidence of a previously unknown locus at chromosome 9p24.3-p23. Parametric two-point analysis suggested linkage with the greatest LOD score of 3.42 for the marker D9S286 at 9p24.1 at recombination fraction ( θ ) = 0, 90% penetrance value and 1% phenocopy rate. The highest multipoint LODscore of 3.42 was obtained for same marker at 9p24. The critical genetic interval of about 10 Mb of DNA was defined by the markers D9S917 and D9S168 corresponding to the centromere-distal and centromere-proximal recombination boundaries, respectively. This observation along with our previous findings of hot water genetic loci at 10q21.3-q22.3 (OMIM: 613339) and 4q24-q28 (OMIM: 613340), indicates unanticipated genetic heterogeneity for the disorder in families from a relatively small geographic region in the southern parts of India.

Mosaic isochromosome 15q and maternal uniparental isodisomy for chromosome 15 in a patient with morbid obesity and variant PWS-like phenotype.

PubMed

Wang, Jia-Chi; Vaccarello-Cruz, Mary; Ross, Leslie; Owen, Renius; Pratt, Victoria M; Lightman, Katherine; Liu, Yan; Hafezi, Katayoun; Cherif, Dhia; Sahoo, Trilochan

2013-07-01

Angelman and Prader-Willi syndromes are reciprocal imprinting disorders caused by loss of maternally or paternally expressed genes, respectively, within 15q11.2-q13. Angelman syndrome (AS; OMIM 105830) is a neurodevelopmental disorder and is due to the loss of maternally expressed UBE3A gene. Prader-Willi syndrome (PWS; OMIM 176270) is a clinically distinct disorder caused by the loss of paternally expressed genes in the human chromosome region 15q11.2-q13. Recently published data strongly suggest a role for the paternally expressed small nucleolar RNA (snoRNA) cluster, SNORD116, in PWS etiology. Uniparental disomy (UPD) 15 is one of the important causes of PWS and AS. Interestingly, balanced and unbalanced chromosomal aberrations in the form of Robertsonian translocation, isochromosomes, supernumerary marker chromosomes and copy number variations have been strongly linked with the occurrence of UPD. Here we report on a very unique case with a mosaic isochromosome for the entire long arm of 15, that is, i(15)(q10), resulting in mosaic uniparental isodisomy for 15q and with no copy number alterations. This is the first report of UPD15 constituted by a mosaic, but copy number neutral chromosomal rearrangement in a patient with a variant PWS-like phenotype. Copyright © 2013 Wiley Periodicals, Inc.

Database resources of the National Center for Biotechnology Information

PubMed Central

Wheeler, David L.; Barrett, Tanya; Benson, Dennis A.; Bryant, Stephen H.; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M.; DiCuccio, Michael; Edgar, Ron; Federhen, Scott; Feolo, Michael; Geer, Lewis Y.; Helmberg, Wolfgang; Kapustin, Yuri; Khovayko, Oleg; Landsman, David; Lipman, David J.; Madden, Thomas L.; Maglott, Donna R.; Miller, Vadim; Ostell, James; Pruitt, Kim D.; Schuler, Gregory D.; Shumway, Martin; Sequeira, Edwin; Sherry, Steven T.; Sirotkin, Karl; Souvorov, Alexandre; Starchenko, Grigory; Tatusov, Roman L.; Tatusova, Tatiana A.; Wagner, Lukas; Yaschenko, Eugene

2008-01-01

In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data available through NCBI's web site. NCBI resources include Entrez, the Entrez Programming Utilities, My NCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link, Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genome, Genome Project and related tools, the Trace, Assembly, and Short Read Archives, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups, Influenza Viral Resources, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Entrez Probe, GENSAT, Database of Genotype and Phenotype, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool and the PubChem suite of small molecule databases. Augmenting the web applications are custom implementations of the BLAST program optimized to search specialized data sets. These resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov. PMID:18045790

Effect of Variable Manning Coefficients on Tsunami Inundation

NASA Astrophysics Data System (ADS)

Barberopoulou, A.; Rees, D.

2017-12-01

Numerical simulations are commonly used to help estimate tsunami hazard, improve evacuation plans, issue or cancel tsunami warnings, inform forecasting and hazard assessments and have therefore become an integral part of hazard mitigation among the tsunami community. Many numerical codes exist for simulating tsunamis, most of which have undergone extensive benchmarking and testing. Tsunami hazard or risk assessments employ these codes following a deterministic or probabilistic approach. Depending on the scope these studies may or may not consider uncertainty in the numerical simulations, the effects of tides, variable friction or estimate financial losses, none of which are necessarily trivial. Distributed manning coefficients, the roughness coefficients used in hydraulic modeling, are commonly used in simulating both riverine and pluvial flood events however, their use in tsunami hazard assessments is primarily part of limited scope studies and for the most part, not a standard practice. For this work, we investigate variations in manning coefficients and their effects on tsunami inundation extent, pattern and financial loss. To assign manning coefficients we use land use maps that come from the New Zealand Land Cover Database (LCDB) and more recent data from the Ministry of the Environment. More than 40 classes covering different types of land use are combined into major classes such as cropland, grassland and wetland representing common types of land use in New Zealand, each of which is assigned a unique manning coefficient. By utilizing different data sources for variable manning coefficients, we examine the impact of data sources and classification methodology on the accuracy of model outputs.

An integrative approach to ortholog prediction for disease-focused and other functional studies.

PubMed

Hu, Yanhui; Flockhart, Ian; Vinayagam, Arunachalam; Bergwitz, Clemens; Berger, Bonnie; Perrimon, Norbert; Mohr, Stephanie E

2011-08-31

Mapping of orthologous genes among species serves an important role in functional genomics by allowing researchers to develop hypotheses about gene function in one species based on what is known about the functions of orthologs in other species. Several tools for predicting orthologous gene relationships are available. However, these tools can give different results and identification of predicted orthologs is not always straightforward. We report a simple but effective tool, the Drosophila RNAi Screening Center Integrative Ortholog Prediction Tool (DIOPT; http://www.flyrnai.org/diopt), for rapid identification of orthologs. DIOPT integrates existing approaches, facilitating rapid identification of orthologs among human, mouse, zebrafish, C. elegans, Drosophila, and S. cerevisiae. As compared to individual tools, DIOPT shows increased sensitivity with only a modest decrease in specificity. Moreover, the flexibility built into the DIOPT graphical user interface allows researchers with different goals to appropriately 'cast a wide net' or limit results to highest confidence predictions. DIOPT also displays protein and domain alignments, including percent amino acid identity, for predicted ortholog pairs. This helps users identify the most appropriate matches among multiple possible orthologs. To facilitate using model organisms for functional analysis of human disease-associated genes, we used DIOPT to predict high-confidence orthologs of disease genes in Online Mendelian Inheritance in Man (OMIM) and genes in genome-wide association study (GWAS) data sets. The results are accessible through the DIOPT diseases and traits query tool (DIOPT-DIST; http://www.flyrnai.org/diopt-dist). DIOPT and DIOPT-DIST are useful resources for researchers working with model organisms, especially those who are interested in exploiting model organisms such as Drosophila to study the functions of human disease genes.

The University of Minnesota Biocatalysis/Biodegradation Database: specialized metabolism for functional genomics.

PubMed Central

Ellis, L B; Hershberger, C D; Wackett, L P

1999-01-01

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD, http://www.labmed.umn.edu/umbbd/i nde x.html) first became available on the web in 1995 to provide information on microbial biocatalytic reactions of, and biodegradation pathways for, organic chemical compounds, especially those produced by man. Its goal is to become a representative database of biodegradation, spanning the diversity of known microbial metabolic routes, organic functional groups, and environmental conditions under which biodegradation occurs. The database can be used to enhance understanding of basic biochemistry, biocatalysis leading to speciality chemical manufacture, and biodegradation of environmental pollutants. It is also a resource for functional genomics, since it contains information on enzymes and genes involved in specialized metabolism not found in intermediary metabolism databases, and thus can assist in assigning functions to genes homologous to such less common genes. With information on >400 reactions and compounds, it is poised to become a resource for prediction of microbial biodegradation pathways for compounds it does not contain, a process complementary to predicting the functions of new classes of microbial genes. PMID:9847233

Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies.

PubMed

Johns, N; Tan, B H; MacMillan, M; Solheim, T S; Ross, J A; Baracos, V E; Damaraju, S; Fearon, K C H

2014-12-01

Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986-2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and to develop their potential as susceptibility biomarkers of cachexia.

MitProNet: A Knowledgebase and Analysis Platform of Proteome, Interactome and Diseases for Mammalian Mitochondria

PubMed Central

Mao, Song; Chai, Xiaoqiang; Hu, Yuling; Hou, Xugang; Tang, Yiheng; Bi, Cheng; Li, Xiao

2014-01-01

Mitochondrion plays a central role in diverse biological processes in most eukaryotes, and its dysfunctions are critically involved in a large number of diseases and the aging process. A systematic identification of mitochondrial proteomes and characterization of functional linkages among mitochondrial proteins are fundamental in understanding the mechanisms underlying biological functions and human diseases associated with mitochondria. Here we present a database MitProNet which provides a comprehensive knowledgebase for mitochondrial proteome, interactome and human diseases. First an inventory of mammalian mitochondrial proteins was compiled by widely collecting proteomic datasets, and the proteins were classified by machine learning to achieve a high-confidence list of mitochondrial proteins. The current version of MitProNet covers 1124 high-confidence proteins, and the remainders were further classified as middle- or low-confidence. An organelle-specific network of functional linkages among mitochondrial proteins was then generated by integrating genomic features encoded by a wide range of datasets including genomic context, gene expression profiles, protein-protein interactions, functional similarity and metabolic pathways. The functional-linkage network should be a valuable resource for the study of biological functions of mitochondrial proteins and human mitochondrial diseases. Furthermore, we utilized the network to predict candidate genes for mitochondrial diseases using prioritization algorithms. All proteins, functional linkages and disease candidate genes in MitProNet were annotated according to the information collected from their original sources including GO, GEO, OMIM, KEGG, MIPS, HPRD and so on. MitProNet features a user-friendly graphic visualization interface to present functional analysis of linkage networks. As an up-to-date database and analysis platform, MitProNet should be particularly helpful in comprehensive studies of complicated biological mechanisms underlying mitochondrial functions and human mitochondrial diseases. MitProNet is freely accessible at http://bio.scu.edu.cn:8085/MitProNet. PMID:25347823

FINDbase: a relational database recording frequencies of genetic defects leading to inherited disorders worldwide.

PubMed

van Baal, Sjozef; Kaimakis, Polynikis; Phommarinh, Manyphong; Koumbi, Daphne; Cuppens, Harry; Riccardino, Francesca; Macek, Milan; Scriver, Charles R; Patrinos, George P

2007-01-01

Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface. Databaseaccess is free of charge and there are no registration requirements for data querying. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'.

Electroacupuncture for women with stress urinary incontinence: Protocol for a systematic review and meta-analysis.

PubMed

Huang, Weixin; Li, Xiaohui; Wang, Yuanping; Yan, Xia; Wu, Siping

2017-12-01

Stress urinary incontinence (SUI) is a widespread complaint in the adult women. Electroacupuncture has been widely applied in the treatment of SUI. But its efficacy has not been evaluated scientifically and systematically. Therefore, we provide a protocol of systematic evaluation to assess the effectiveness and safety of electroacupuncture treatment on women with SUI. The retrieved databases include 3 English literature databases, namely PubMed, Embase, and Cochrane Library, and 3 Chinese literature databases, namely Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang Database. The randomized controlled trials (RCTs) of the electroacupuncture treatment on women with SUI will be searched in the above-mentioned databases from the time when the respective databases were established to December 2017. The change from baseline in the amount of urine leakage measured by the 1-hour pad test will be accepted as the primary outcomes. We will use RevMan V.5.3 software as well to compute the data synthesis carefully when a meta-analysis is allowed. This study will provide a high-quality synthesis to assess the effectiveness and safety of electroacupuncture treatment on women with SUI. The conclusion of our systematic review will provide evidence to judge whether electroacupuncture is an effective intervention for women with SUI. PROSPERO CRD42017070947.

Rational Design of QCM-D Virtual Sensor Arrays Based on Film Thickness, Viscoelasticity, and Harmonics for Vapor Discrimination.

PubMed

Speller, Nicholas C; Siraj, Noureen; Regmi, Bishnu P; Marzoughi, Hassan; Neal, Courtney; Warner, Isiah M

2015-01-01

Herein, we demonstrate an alternative strategy for creating QCM-based sensor arrays by use of a single sensor to provide multiple responses per analyte. The sensor, which simulates a virtual sensor array (VSA), was developed by depositing a thin film of ionic liquid, either 1-octyl-3-methylimidazolium bromide ([OMIm][Br]) or 1-octyl-3-methylimidazolium thiocyanate ([OMIm][SCN]), onto the surface of a QCM-D transducer. The sensor was exposed to 18 different organic vapors (alcohols, hydrocarbons, chlorohydrocarbons, nitriles) belonging to the same or different homologous series. The resulting frequency shifts (Δf) were measured at multiple harmonics and evaluated using principal component analysis (PCA) and discriminant analysis (DA) which revealed that analytes can be classified with extremely high accuracy. In almost all cases, the accuracy for identification of a member of the same class, that is, intraclass discrimination, was 100% as determined by use of quadratic discriminant analysis (QDA). Impressively, some VSAs allowed classification of all 18 analytes tested with nearly 100% accuracy. Such results underscore the importance of utilizing lesser exploited properties that influence signal transduction. Overall, these results demonstrate excellent potential of the virtual sensor array strategy for detection and discrimination of vapor phase analytes utilizing the QCM. To the best of our knowledge, this is the first report on QCM VSAs, as well as an experimental sensor array, that is based primarily on viscoelasticity, film thickness, and harmonics.

No association between GSTM1 and GSTT1 genetic polymorphisms and susceptibility to opium sap dependence.

PubMed

Saify, Khyber; Khalighinasab, Mohammad Rashid; Saadat, Mostafa

2016-03-01

Glutathione S-transferases (GSTs; EC: 2.5.1.18) are a ubiquitous family of eukaryotic and prokaryotic phase II metabolic isozymes. Genes encoding GSTM1 (OMIM: 138350), and GSTT1 (OMIM: 600436) are members of class mu and theta, respectively. The most common polymorphism in the GSTM1 is a deletion of the whole GSTM1 gene with a lack of enzyme activity. A homozygous deletion in the GSTT1 has also been reported (null genotypes of GSTT1). The aim of the present study was to investigate the association between GSTM1 and GSTT1 polymorphisms and risk of dependency to opium sap. The present study was performed in Shiraz (southern Iran). In total, 71 males dependent to opium sap and 590 healthy males (as a control group) were included in this study. The genotypes of GSTM1 and GSTT1 polymorphisms were determined by PCR. Our data indicate that neither GSTM1 (OR=0.78, 95% CI: 0.47-1.27, P=0.325) nor GSTT1 (OR=1.25, 95% CI: 0.70-2.21, P=0.442) null genotypes significantly associated with the risk of opium sap dependence. There is no additive effect of the null genotypes of GSTT1 and GSTM1 in relation to the risk of dependency to opium sap. The present study indicated that the null genotypes of GSTT1 and GSTM1 are not risk factor for opium sap dependence.

MeCP2 co-ordinates liver lipid metabolism with the NCoR1/HDAC3 corepressor complex

PubMed Central

Kyle, Stephanie M.; Saha, Pradip K.; Brown, Hannah M.; Chan, Lawrence C.; Justice, Monica J.

2016-01-01

Rett syndrome (RTT; OMIM 312750), a progressive neurological disorder, is caused by mutations in methyl-CpG-binding protein 2 (MECP2; OMIM 300005), a ubiquitously expressed factor. A genetic suppressor screen designed to identify therapeutic targets surprisingly revealed that downregulation of the cholesterol biosynthesis pathway improves neurological phenotypes in Mecp2 mutant mice. Here, we show that MeCP2 plays a direct role in regulating lipid metabolism. Mecp2 deletion in mice results in a host of severe metabolic defects caused by lipid accumulation, including insulin resistance, fatty liver, perturbed energy utilization, and adipose inflammation by macrophage infiltration. We show that MeCP2 regulates lipid homeostasis by anchoring the repressor complex containing NCoR1 and HDAC3 to its lipogenesis targets in hepatocytes. Consistently, we find that liver targeted deletion of Mecp2 causes fatty liver disease and dyslipidemia similar to HDAC3 liver-specific deletion. These findings position MeCP2 as a novel component in metabolic homeostasis. Rett syndrome patients also show signs of peripheral dyslipidemia; thus, together these data suggest that RTT should be classified as a neurological disorder with systemic metabolic components. We previously showed that treatment of Mecp2 mice with statin drugs alleviated motor symptoms and improved health and longevity. Lipid metabolism is a highly treatable target; therefore, our results shed light on new metabolic pathways for treatment of Rett syndrome. PMID:27288453

Diagnostic Assessment of Troubleshooting Skill in an Intelligent Tutoring System

DTIC Science & Technology

1994-03-01

the information that can be provided from studying gauges and indicators and conventional test equipment procedures. Experts are particularly adept at...uses the results of the strategy and action evaluator to update the student profile, represented as a network, using the ERGO ( Noetic Systems, 1993...1990). Individualized tutoring using an intelligent fuzzy temporal relational database. International Tournal of Man-Machine Studies . & 409-429. 𔄁. 34

Aminoacyl-tRNA synthetases database Y2K

PubMed Central

Szymanski, Maciej; Barciszewski, Jan

2000-01-01

The aminoacyl-tRNA synthetases (AARS) are a diverse group of enzymes that ensure the fidelity of transfer of genetic information from DNA into protein. They catalyse the attachment of amino acids to transfer RNAs and thereby establish the rules of the genetic code by virtue of matching the nucleotide triplet of the anticodon with its cognate amino acid. Currently, 818 AARS primary structures have been reported from archaebacteria, eubacteria, mitochondria, chloroplasts and eukaryotic cells. The database is a compilation of the amino acid sequences of all AARSs, known to date, which are available as separate entries or alignments of related proteins via the WWW at http://rose.man.poznan.pl/aars/index.html PMID:10592262

Aminoacyl-tRNA synthetases database Y2K.

PubMed

Szymanski, M; Barciszewski, J

2000-01-01

The aminoacyl-tRNA synthetases (AARS) are a diverse group of enzymes that ensure the fidelity of transfer of genetic information from DNA into protein. They catalyse the attachment of amino acids to transfer RNAs and thereby establish the rules of the genetic code by virtue of matching the nucleotide triplet of the anticodon with its cognate amino acid. Currently, 818 AARS primary structures have been reported from archaebacteria, eubacteria, mitochondria, chloro-plasts and eukaryotic cells. The database is a compilation of the amino acid sequences of all AARSs, known to date, which are available as separate entries or alignments of related proteins via the WWW at http://rose.man.poznan.pl/aars/index.html

Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype.

PubMed

Hoppman-Chaney, N; Wain, K; Seger, P R; Superneau, D W; Hodge, J C

2013-04-01

The 15q13.3 microdeletion syndrome (OMIM #612001) is characterized by a wide range of phenotypic features, including intellectual disability, seizures, autism, and psychiatric conditions. This deletion is inherited in approximately 75% of cases and has been found in mildly affected and normal parents, consistent with variable expressivity and incomplete penetrance. The common deletion is approximately 2 Mb and contains several genes; however, the gene(s) responsible for the resulting clinical features have not been clearly defined. Recently, four probands were reported with small deletions including only the CHRNA7 gene. These patients showed a wide range of phenotypic features similar to those associated with the larger 15q13.3 microdeletion. To further correlate genotype and phenotype, we queried our database of >15,000 patients tested in the Mayo Clinic Cytogenetics Laboratory from 2008 to 2011 and identified 19 individuals (10 probands and 9 family members) with isolated heterozygous CHRNA7 gene deletions. All but two infants displayed multiple features consistent with 15q13.3 microdeletion syndrome. We also identified the first de novo deletion confined to CHRNA7 as well as the second known case with homozygous deletion of CHRNA7 only. These results provide further evidence implicating CHRNA7 as the gene responsible for the clinical findings associated with 15q13.3 microdeletion. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Systematic review of autosomal recessive ataxias and proposal for a classification.

PubMed

Beaudin, Marie; Klein, Christopher J; Rouleau, Guy A; Dupré, Nicolas

2017-01-01

The classification of autosomal recessive ataxias represents a significant challenge because of high genetic heterogeneity and complex phenotypes. We conducted a comprehensive systematic review of the literature to examine all recessive ataxias in order to propose a new classification and properly circumscribe this field as new technologies are emerging for comprehensive targeted gene testing. We searched Pubmed and Embase to identify original articles on recessive forms of ataxia in humans for which a causative gene had been identified. Reference lists and public databases, including OMIM and GeneReviews, were also reviewed. We evaluated the clinical descriptions to determine if ataxia was a core feature of the phenotype and assessed the available evidence on the genotype-phenotype association. Included disorders were classified as primary recessive ataxias, as other complex movement or multisystem disorders with prominent ataxia, or as disorders that may occasionally present with ataxia. After removal of duplicates, 2354 references were reviewed and assessed for inclusion. A total of 130 articles were completely reviewed and included in this qualitative analysis. The proposed new list of autosomal recessive ataxias includes 45 gene-defined disorders for which ataxia is a core presenting feature. We propose a clinical algorithm based on the associated symptoms. We present a new classification for autosomal recessive ataxias that brings awareness to their complex phenotypes while providing a unified categorization of this group of disorders. This review should assist in the development of a consensus nomenclature useful in both clinical and research applications.

Shwachman-Bodian-Diamond syndrome: metaphyseal chondrodysplasia in children with pancreatic insufficiency and neutropenia.

PubMed

Levin, Terry L; Mäkitie, Outi; Berdon, Walter E; Lachman, Ralph S

2015-07-01

Shwachman-Bodian-Diamond syndrome (OMIM 260400) was identified in 1964 by pediatricians Harry Shwachman, a leader in cystic fibrosis, and Louis K. Diamond, a hematologist, along with pediatrician and morbid anatomist Martin Bodian. Initially the syndrome's clinical presentation included exocrine pancreatic insufficiency (lipomatous replacement of the pancreas) and neutropenia. In 1967 skeletal changes of metaphyseal chondrodysplasia were also described, completing the triad of findings; these abnormalities are present in all affected children and should be viewed as an integral feature of the syndrome, also called Shwachman-Diamond syndrome.

A DBMS architecture for global change research

NASA Astrophysics Data System (ADS)

Hachem, Nabil I.; Gennert, Michael A.; Ward, Matthew O.

1993-08-01

The goal of this research is the design and development of an integrated system for the management of very large scientific databases, cartographic/geographic information processing, and exploratory scientific data analysis for global change research. The system will represent both spatial and temporal knowledge about natural and man-made entities on the eath's surface, following an object-oriented paradigm. A user will be able to derive, modify, and apply, procedures to perform operations on the data, including comparison, derivation, prediction, validation, and visualization. This work represents an effort to extend the database technology with an intrinsic class of operators, which is extensible and responds to the growing needs of scientific research. Of significance is the integration of many diverse forms of data into the database, including cartography, geography, hydrography, hypsography, images, and urban planning data. Equally important is the maintenance of metadata, that is, data about the data, such as coordinate transformation parameters, map scales, and audit trails of previous processing operations. This project will impact the fields of geographical information systems and global change research as well as the database community. It will provide an integrated database management testbed for scientific research, and a testbed for the development of analysis tools to understand and predict global change.

ChlamyCyc: an integrative systems biology database and web-portal for Chlamydomonas reinhardtii.

PubMed

May, Patrick; Christian, Jan-Ole; Kempa, Stefan; Walther, Dirk

2009-05-04

The unicellular green alga Chlamydomonas reinhardtii is an important eukaryotic model organism for the study of photosynthesis and plant growth. In the era of modern high-throughput technologies there is an imperative need to integrate large-scale data sets from high-throughput experimental techniques using computational methods and database resources to provide comprehensive information about the molecular and cellular organization of a single organism. In the framework of the German Systems Biology initiative GoFORSYS, a pathway database and web-portal for Chlamydomonas (ChlamyCyc) was established, which currently features about 250 metabolic pathways with associated genes, enzymes, and compound information. ChlamyCyc was assembled using an integrative approach combining the recently published genome sequence, bioinformatics methods, and experimental data from metabolomics and proteomics experiments. We analyzed and integrated a combination of primary and secondary database resources, such as existing genome annotations from JGI, EST collections, orthology information, and MapMan classification. ChlamyCyc provides a curated and integrated systems biology repository that will enable and assist in systematic studies of fundamental cellular processes in Chlamydomonas. The ChlamyCyc database and web-portal is freely available under http://chlamycyc.mpimp-golm.mpg.de.

Control system software, simulation, and robotic applications

NASA Technical Reports Server (NTRS)

Frisch, Harold P.

1991-01-01

All essential existing capabilities needed to create a man-machine interaction dynamics and performance (MMIDAP) capability are reviewed. The multibody system dynamics software program Order N DISCOS will be used for machine and musculo-skeletal dynamics modeling. The program JACK will be used for estimating and animating whole body human response to given loading situations and motion constraints. The basic elements of performance (BEP) task decomposition methodologies associated with the Human Performance Institute database will be used for performance assessment. Techniques for resolving the statically indeterminant muscular load sharing problem will be used for a detailed understanding of potential musculotendon or ligamentous fatigue, pain, discomfort, and trauma. The envisioned capacity is to be used for mechanical system design, human performance assessment, extrapolation of man/machine interaction test data, biomedical engineering, and soft prototyping within a concurrent engineering (CE) system.

The Roberts syndrome/SC phocomelia spectrum--a case report of an adult with review of the literature.

PubMed

Goh, Elaine Suk-Ying; Li, Chumei; Horsburgh, Sheri; Kasai, Yumi; Kolomietz, Elena; Morel, Chantal France

2010-02-01

Roberts syndrome (RBS) (OMIM #268300) is a rare autosomal recessive disorder characterized by tetraphocomelia (symmetrical limb reduction), craniofacial anomalies, growth retardation, mental retardation, cardiac and renal abnormalities. The syndrome is caused by mutations in the ESCO2 (establishment of cohesion 1 homolog 2) (Entrez 609353) gene, which is located at 8p21.1, and encodes a protein essential in establishing sister chromatid cohesion during S phase. SC phocomelia (SC) (OMIM #269000), has less severe symmetric limb reduction, flexion contractures of various joints, minor facial anomalies, growth retardation and occasionally, mental retardation. These two syndromes can be considered part of a spectrum, with RBS at the most severe range in which severely affected infants may be stillborn or die in the post-natal period, while individuals with SC phocomelia represent the milder end of the spectrum and typically survive to adulthood. In both presentations, karyotype investigations characteristically reveal premature centromere separation (PCS), otherwise known as heterochromatin repulsion or puffing. There is little literature about the follow-up of adults with the spectrum of RBS/SC phocomelia or their recommended management. We report on an adult presentation of RBS/SC phocomelia spectrum disorder with a history of major cardiac malformation in childhood, normal limbs on physical examination, mild facial anomalies, mild learning difficulties, and PCS. Molecular studies of ESCO2 have confirmed the diagnosis. A literature review, focussing on adult manifestations of this condition and a discussion of follow-up guidelines are presented. Copyright 2010 Wiley-Liss, Inc.

Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer.

PubMed

Jamhiri, Iman; Saadat, Iraj; Omidvari, Shahpour

2017-06-01

Oxidative stress is significant in numerous types of disease including cancer. To protect cells and organs against reactive oxygen species (ROS), the body has evolved an antioxidant protection system that involved in the detoxification of ROS. Single nucleotide polymorphisms (SNP) of anti-oxidative enzymes may dramatically change the activity of the encoded proteins; therefore, certain alleles can be established as risk factors for some kind of multi-factorial diseases including cancer. In present study we investigate the possible association between polymorphisms of superoxide dismutase 1 ( SOD1 , OMIM: 147450) and catalase ( CAT , OMIM: 115500) genes and the risk of colorectal cancer (CRC). The study included 204 colorectal cancer patients and 239 healthy control group matched for gender and age. Genotyping of SOD1 A251G and CAT C-262T were done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. There was no significant association between CAT C-262T polymorphism and susceptibility to CRC (P>0.05). The carries of the G allele of SOD1 significantly showed higher prevalence in CRC patients compared with the control group (OR=1.84, 95% CI=1.13-2.98, P=0.013). We assessed the effect of combination of genotypes of the study polymorphisms on the risk of CRC. We found that the combination of AG+GG ( SOD1 ) and CC ( CAT ) increases the risk of developing CRC (OR=2.38, 95% CI=1.25-4.52, P=0.008).

Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer

PubMed Central

Jamhiri, Iman; Saadat, Iraj; Omidvari, Shahpour

2017-01-01

Oxidative stress is significant in numerous types of disease including cancer. To protect cells and organs against reactive oxygen species (ROS), the body has evolved an antioxidant protection system that involved in the detoxification of ROS. Single nucleotide polymorphisms (SNP) of anti-oxidative enzymes may dramatically change the activity of the encoded proteins; therefore, certain alleles can be established as risk factors for some kind of multi-factorial diseases including cancer. In present study we investigate the possible association between polymorphisms of superoxide dismutase 1 (SOD1, OMIM: 147450) and catalase (CAT, OMIM: 115500) genes and the risk of colorectal cancer (CRC). The study included 204 colorectal cancer patients and 239 healthy control group matched for gender and age. Genotyping of SOD1 A251G and CAT C-262T were done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. There was no significant association between CAT C-262T polymorphism and susceptibility to CRC (P>0.05). The carries of the G allele of SOD1 significantly showed higher prevalence in CRC patients compared with the control group (OR=1.84, 95% CI=1.13-2.98, P=0.013). We assessed the effect of combination of genotypes of the study polymorphisms on the risk of CRC. We found that the combination of AG+GG (SOD1) and CC (CAT) increases the risk of developing CRC (OR=2.38, 95% CI=1.25-4.52, P=0.008). PMID:28775994

Predicting the partitioning of biological compounds between room-temperature ionic liquids and water by means of the solvation-parameter model.

PubMed

Padró, Juan M; Ponzinibbio, Agustín; Mesa, Leidy B Agudelo; Reta, Mario

2011-03-01

The partition coefficients, P(IL/w), for different probe molecules as well as for compounds of biological interest between the room-temperature ionic liquids (RTILs) 1-butyl-3-methylimidazolium hexafluorophosphate, [BMIM][PF(6)], 1-hexyl-3-methylimidazolium hexafluorophosphate, [HMIM][PF(6)], 1-octyl-3-methylimidazolium tetrafluoroborate, [OMIM][BF(4)] and water were accurately measured. [BMIM][PF(6)] and [OMIM][BF(4)] were synthesized by adapting a procedure from the literature to a simpler, single-vessel and faster methodology, with a much lesser consumption of organic solvent. We employed the solvation-parameter model to elucidate the general chemical interactions involved in RTIL/water partitioning. With this purpose, we have selected different solute descriptor parameters that measure polarity, polarizability, hydrogen-bond-donor and hydrogen-bond-acceptor interactions, and cavity formation for a set of specifically selected probe molecules (the training set). The obtained multiparametric equations were used to predict the partition coefficients for compounds not present in the training set (the test set), most being of biological interest. Partial solubility of the ionic liquid in water (and water into the ionic liquid) was taken into account to explain the obtained results. This fact has not been deeply considered up to date. Solute descriptors were obtained from the literature, when available, or else calculated through commercial software. An excellent agreement between calculated and experimental log P(IL/w) values was obtained, which demonstrated that the resulting multiparametric equations are robust and allow predicting partitioning for any organic molecule in the biphasic systems studied.

Energy Supply Options for Modernizing Army Heating Systems

DTIC Science & Technology

1999-01-01

Army Regulation (AR) 420-49, Heating, Energy Selection and Fuel Storage, Distribution, and Dispens- ing Systems and Technical Manual (TM) 5-650...analysis. 26 USACERL TR 99/23 HEATMAP uses the AutoLISP program in AutoCAD to take the graphical input to populate a Microsoft® Access database in...of 1992, Subtitle F, Federal Agency Energy Man- agement. Technical Manual (TM) 5-650, Repairs and Utilities: Central Boiler Plants (HQDA, 13 October

Uneventful pregnancy outcome after enzyme replacement therapy with agalsidase beta in a heterozygous female with Fabry disease: A case report.

PubMed

Germain, Dominique P; Bruneval, Patrick; Tran, Thi-Chien; Balouet, Pierre; Richalet, Bernard; Benistan, Karelle

2010-01-01

No reproductive studies have been performed with enzyme replacement therapy (ERT) for Fabry disease (FD, OMIM 301500), a lysosomal storage disorder. Therefore, use during pregnancy is theoretically contraindicated. We report the first case of agalsidase beta treatment throughout pregnancy. High-range proteinuria remained stable and the patient gave birth to a healthy boy after an uncomplicated pregnancy. The decision to administer ERT during pregnancy should be made on an individual basis, considering the FD status and possible risks. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Hydrogenation of Carbon Dioxide to Methane by Ruthenium Nanoparticles in Ionic Liquid.

PubMed

Melo, Catarina I; Szczepańska, Anna; Bogel-Łukasik, Ewa; Nunes da Ponte, Manuel; Branco, Luís C

2016-05-23

The efficient transformation of carbon dioxide into fuels can be an excellent alternative to sequestration. In this work, we describe CO2 hydrogenation to methane in imidazolium-based ionic liquid media, using ruthenium nanoparticles prepared in situ as catalyst. The best yield of methane (69 %) was achieved using 0.24 mol % ruthenium catalyst (in [omim][NTf2 ], 1-octyl-3-methylimidazolium bistrifluoromethanesulfonylimide, at 40 bar of hydrogen pressure plus 40 bar of CO2 pressure, and at 150 °C. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Database Tool for Master Console Operators

NASA Technical Reports Server (NTRS)

Ferrell, Sean

2018-01-01

The Spaceport Command and Control System (SCCS) is the National Aeronautics and Space Administration's (NASA) launch control system for the Orion capsule and Space Launch System, the next generation manned rocket currently in development. This large system requires highly trained and knowledgeable personnel. Master Console Operators (MCO) are currently working on familiarizing themselves with any possible scenario that they may encounter. An intern was recruited to help assist them with creating a tool to use for the process.

Mendel,MD: A user-friendly open-source web tool for analyzing WES and WGS in the diagnosis of patients with Mendelian disorders

PubMed Central

D. Linhares, Natália; Pena, Sérgio D. J.

2017-01-01

Whole exome and whole genome sequencing have both become widely adopted methods for investigating and diagnosing human Mendelian disorders. As pangenomic agnostic tests, they are capable of more accurate and agile diagnosis compared to traditional sequencing methods. This article describes new software called Mendel,MD, which combines multiple types of filter options and makes use of regularly updated databases to facilitate exome and genome annotation, the filtering process and the selection of candidate genes and variants for experimental validation and possible diagnosis. This tool offers a user-friendly interface, and leads clinicians through simple steps by limiting the number of candidates to achieve a final diagnosis of a medical genetics case. A useful innovation is the “1-click” method, which enables listing all the relevant variants in genes present at OMIM for perusal by clinicians. Mendel,MD was experimentally validated using clinical cases from the literature and was tested by students at the Universidade Federal de Minas Gerais, at GENE–Núcleo de Genética Médica in Brazil and at the Children’s University Hospital in Dublin, Ireland. We show in this article how it can simplify and increase the speed of identifying the culprit mutation in each of the clinical cases that were received for further investigation. Mendel,MD proved to be a reliable web-based tool, being open-source and time efficient for identifying the culprit mutation in different clinical cases of patients with Mendelian Disorders. It is also freely accessible for academic users on the following URL: https://mendelmd.org. PMID:28594829

Practice Parameter: Evaluation of the child with microcephaly (an evidence-based review)

PubMed Central

Ashwal, Stephen; Michelson, David; Plawner, Lauren; Dobyns, William B.

2009-01-01

Objective: To make evidence-based recommendations concerning the evaluation of the child with microcephaly. Methods: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a 4-tiered scheme of evidence classification. Results: Microcephaly is an important neurologic sign but there is nonuniformity in its definition and evaluation. Microcephaly may result from any insult that disturbs early brain growth and can be seen in association with hundreds of genetic syndromes. Annually, approximately 25,000 infants in the United States will be diagnosed with microcephaly (head circumference <−2 SD). Few data are available to inform evidence-based recommendations regarding diagnostic testing. The yield of neuroimaging ranges from 43% to 80%. Genetic etiologies have been reported in 15.5% to 53.3%. The prevalence of metabolic disorders is unknown but is estimated to be 1%. Children with severe microcephaly (head circumference <−3 SD) are more likely (∼80%) to have imaging abnormalities and more severe developmental impairments than those with milder microcephaly (−2 to −3 SD; ∼40%). Coexistent conditions include epilepsy (∼40%), cerebral palsy (∼20%), mental retardation (∼50%), and ophthalmologic disorders (∼20% to ∼50%). Recommendations: Neuroimaging may be considered useful in identifying structural causes in the evaluation of the child with microcephaly (Level C). Targeted and specific genetic testing may be considered in the evaluation of the child with microcephaly who has clinical or imaging abnormalities that suggest a specific diagnosis or who shows no evidence of an acquired or environmental etiology (Level C). Screening for coexistent conditions such as cerebral palsy, epilepsy, and sensory deficits may also be considered (Level C). Further study is needed regarding the yield of diagnostic testing in children with microcephaly. GLOSSARY CP = cerebral palsy; GDD = global developmental delay; HC = head circumference; MRE = medically refractory epilepsy; OMIM = Online Mendelian Inheritance in Man. PMID:19752457

Cluster and propensity based approximation of a network

PubMed Central

2013-01-01

Background The models in this article generalize current models for both correlation networks and multigraph networks. Correlation networks are widely applied in genomics research. In contrast to general networks, it is straightforward to test the statistical significance of an edge in a correlation network. It is also easy to decompose the underlying correlation matrix and generate informative network statistics such as the module eigenvector. However, correlation networks only capture the connections between numeric variables. An open question is whether one can find suitable decompositions of the similarity measures employed in constructing general networks. Multigraph networks are attractive because they support likelihood based inference. Unfortunately, it is unclear how to adjust current statistical methods to detect the clusters inherent in many data sets. Results Here we present an intuitive and parsimonious parametrization of a general similarity measure such as a network adjacency matrix. The cluster and propensity based approximation (CPBA) of a network not only generalizes correlation network methods but also multigraph methods. In particular, it gives rise to a novel and more realistic multigraph model that accounts for clustering and provides likelihood based tests for assessing the significance of an edge after controlling for clustering. We present a novel Majorization-Minimization (MM) algorithm for estimating the parameters of the CPBA. To illustrate the practical utility of the CPBA of a network, we apply it to gene expression data and to a bi-partite network model for diseases and disease genes from the Online Mendelian Inheritance in Man (OMIM). Conclusions The CPBA of a network is theoretically appealing since a) it generalizes correlation and multigraph network methods, b) it improves likelihood based significance tests for edge counts, c) it directly models higher-order relationships between clusters, and d) it suggests novel clustering algorithms. The CPBA of a network is implemented in Fortran 95 and bundled in the freely available R package PropClust. PMID:23497424

Overview of the HUPO Plasma Proteome Project: Results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database

DOE Office of Scientific and Technical Information (OSTI.GOV)

Omenn, Gilbert; States, David J.; Adamski, Marcin

2005-08-13

HUPO initiated the Plasma Proteome Project (PPP) in 2002. Its pilot phase has (1) evaluated advantages and limitations of many depletion, fractionation, and MS technology platforms; (2) compared PPP reference specimens of human serum and EDTA, heparin, and citrate-anticoagulated plasma; and (3) created a publicly-available knowledge base (www.bioinformatics. med.umich.edu/hupo/ppp; www.ebi.ac.uk/pride). Thirty-five participating laboratories in 13 countries submitted datasets. Working groups addressed (a) specimen stability and protein concentrations; (b) protein identifications from 18 MS/MS datasets; (c) independent analyses from raw MS-MS spectra; (d) search engine performance, subproteome analyses, and biological insights; (e) antibody arrays; and (f) direct MS/SELDI analyses. MS-MS datasetsmore » had 15 710 different International Protein Index (IPI) protein IDs; our integration algorithm applied to multiple matches of peptide sequences yielded 9504 IPI proteins identified with one or more peptides and 3020 proteins identified with two or more peptides (the Core Dataset). These proteins have been characterized with Gene Ontology, InterPro, Novartis Atlas, OMIM, and immunoassay based concentration determinations. The database permits examination of many other subsets, such as 1274 proteins identified with three or more peptides. Reverse protein to DNA matching identified proteins for 118 previously unidentified ORFs. We recommend use of plasma instead of serum, with EDTA (or citrate) for anticoagulation. To improve resolution, sensitivity and reproducibility of peptide identifications and protein matches, we recommend combinations of depletion, fractionation, and MS/MS technologies, with explicit criteria for evaluation of spectra, use of search algorithms, and integration of homologous protein matches. This Special Issue of PROTEOMICS presents papers integral to the collaborative analysis plus many reports of supplementary work on various aspects of the PPP workplan. These PPP results on complexity, dynamic range, incomplete sampling, false-positive matches, and integration of diverse datasets for plasma and serum proteins lay a foundation for development and validation of circulating protein biomarkers in health and disease.« less

PVRL1 as a Candidate Gene for Nonsyndromic Cleft Lip With or Without Cleft Palate: No Evidence for the Involvement of Common or Rare Variants in Southern Han Chinese Patients

PubMed Central

Cheng, Hong-Qiu; Huang, En-Min; Xu, Ming-Yan; Shu, Shen-You

2012-01-01

The poliovirus receptor related-1 (PVRL1) gene encodes nectin-1, a cell–cell adhesion molecule (OMIM #600644), and is mutated in the cleft lip with or without cleft palate/ectodermal dysplasia-1 syndrome (CLPED1, OMIM #225000). In addition, PVRL1 mutations have been associated with nonsyndromic cleft lip with or without a cleft palate (NSCL/P) in studies of multiethnic samples. To investigate the possible involvement of this gene in southern Han Chinese NSCL/P patients, we performed (i) a case–control association study, and (ii) a resequencing study. A set of 470 patients with NSCL/P and 693 controls were recruited, and a total of 45 tagging single-nucleotide polymorphisms (SNPs) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In the resequencing study, the coding regions of the PVRL1 α isoform were direct sequenced in 45 trios from multiply affected families. One (rs7128327) of the 45 tested SNPs showed a trend toward statistical significance in the genotypic-level chi-square test (p=0.009567). However, this result did not withstand correction for multiple testing. Likewise, sliding window haplotype analyses consisting of two, three, or four SNPs failed to detect any positive association. Resequencing analysis also failed to identify any novel rare sequence variants. In conclusion, the present study provided no support for the hypothesis that common or rare variants in PVRL1 play a significant role in NSCL/P development in the southern Han Chinese population. This is the first study that has used tagging SNPs covering all the coding and noncoding regions to search for common NSCL/P-associated mutations of PVRL1. PMID:22455396

Stir bar sorptive extraction and high performance liquid chromatographic determination of carvedilol in human serum using two different polymeric phases and an ionic liquid as desorption solvent.

PubMed

Talebpour, Zahra; Taraji, Maryam; Adib, Nuoshin

2012-05-04

This article presents a method employing stir bar coated with a film of poly (methyl methacrylate/ethyleneglycol dimethacrylate) (PA-EG) and polydimethylsiloxane (PDMS) in combination with liquid desorption (LD) using ionic liquid, followed by high performance liquid chromatography (HPLC) equipped with ultraviolet (UV) detection for the determination of carvedilol in human serum samples. Stir bar sorptive extraction (SBSE) variables, such as desorption and extraction time and temperature, desorption solvent and pH of the matrix were optimized, in order to achieve suitable analytical sensitivity in a short period of time. Also, the concentration effect of 1-methyl-3-octylimidazolium tetrafluoroborate [Omim][BF4] ionic liquid on the efficiency of LD was investigated. A comparison between PA-EG/SBSE and PDMS/SBSE was made by calculating the experimental recovery and partition coefficient (K), where PA-EG phase demonstrated to be an excellent alternative for the enrichment of the carvedilol from serum samples. The effect of [Omim][BF4] on carryover was studied and no carryover was observed. Under optimized experimental conditions, the analytical performance showed excellent linear dynamic range, with correlation coefficients higher than 0.999 and limits of detection and quantification of 0.3 and 1.0 ng mL(-1), respectively. Intra- and inter-day recovery ranged from 94 to 103% and the coefficients of variations were less than 3.2%. The proposed method was shown to be simple, highly sensitive and suitable for the measurement of trace concentration levels of carvedilol in biological fluid media. Copyright © 2012 Elsevier B.V. All rights reserved.

Identification of a novel mutation in RIPK4 in a kindred with phenotypic features of Bartsocas-Papas and CHAND syndromes.

PubMed

Gollasch, Benjamin; Basmanav, Fitnat Buket; Nanda, Arti; Fritz, Günter; Mahmoudi, Hassnaa; Thiele, Holger; Wehner, Maria; Wolf, Sabrina; Altmüller, Janine; Nürnberg, Peter; Frank, Jorge; Betz, Regina C

2015-11-01

Three children from an expanded consanguineous Kuwaiti kindred presented with ankyloblepharon, sparse and curly hair, and hypoplastic nails, suggestive of CHAND syndrome (OMIM 214350) that belongs to the heterogeneous spectrum of ectodermal dysplasias. After exclusion of pathogenic mutations in TP63 we performed homozygosity mapping, followed by exome sequencing of one affected individual. We initially identified three homozygous mutations in the linked region, located in PWP2, MX2 and RIPK4. Recently, mutations in RIPK4 have been reported in Bartsocas-Papas syndrome (OMIM 263650) that shows overlapping clinical symptoms with the phenotype observed in the affected individuals studied here. Subsequent analysis of affected and non-affected family members showed that mutation c.850G>A (p.Glu284Lys) in RIPK4 was in complete segregation with the disease phenotype, in accordance with an autosomal recessive inheritance pattern, thus supporting pathogenicity of this variant. Interestingly, however, our patients did not have cleft lip/palate, a common feature encountered in Bartsocas-Papas syndrome. Whereas in Bartsocas-Papas syndromes missense mutations are usually located within the serin/threonin kinase of RIPK4, the mutation detected in our family resides just outside of the kinase domain, which could explain the milder phenotype. Our data raise the question if CHAND syndrome indeed is a distinct entity. Alternatively, CHAND and Bartsocas-Papas syndrome might be allelic disorders or RIPK4 mutations could confer varying degrees of phenotypic severity, depending on their localization within or outside functionally important domains. Our findings indicate that making an accurate diagnosis based only on the prevailing clinical symptoms is challenging. © 2015 Wiley Periodicals, Inc.

Taxonomy of rare genetic metabolic bone disorders.

PubMed

Masi, L; Agnusdei, D; Bilezikian, J; Chappard, D; Chapurlat, R; Cianferotti, L; Devolgelaer, J-P; El Maghraoui, A; Ferrari, S; Javaid, M K; Kaufman, J-M; Liberman, U A; Lyritis, G; Miller, P; Napoli, N; Roldan, E; Papapoulos, S; Watts, N B; Brandi, M L

2015-10-01

This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

Circadian abnormalities in mouse models of Smith-Magenis syndrome: evidence for involvement of RAI1.

PubMed

Lacaria, Melanie; Gu, Wenli; Lupski, James R

2013-07-01

Smith-Magenis syndrome (SMS; OMIM 182290) is a genomic disorder characterized by multiple congenital anomalies, intellectual disability, behavioral abnormalities, and disordered sleep resulting from an ~3.7 Mb deletion copy number variant (CNV) on chromosome 17p11.2 or from point mutations in the gene RAI1. The reciprocal duplication of this region results in another genomic disorder, Potocki-Lupski syndrome (PTLS; OMIM 610883), characterized by autism, intellectual disability, and congenital anomalies. We previously used chromosome-engineering and gene targeting to generate mouse models for PTLS (Dp(11)17/+), and SMS due to either deletion CNV or gene knock-out (Df(11)17-2/+ and Rai1(+/-) , respectively) and we observed phenotypes in these mouse models consistent with their associated human syndromes. To investigate the contribution of individual genes to the circadian phenotypes observed in SMS, we now report the analysis of free-running period lengths in Rai1(+/-) and Df(11)17-2/+ mice, as well as in mice deficient for another known circadian gene mapping within the commonly deleted/duplicated region, Dexras1, and we compare these results to those previously observed in Dp(11)17/+ mice. Reduced free-running period lengths were seen in Df(11)17-2/+, Rai1(+/-) , and Dexras1(-/-) , but not Dexras1(+/-) mice, suggesting that Rai1 may be the primary gene underlying the circadian defects in SMS. However, we cannot rule out the possibility that cis effects between multiple haploinsufficient genes in the SMS critical interval (e.g., RAI1 and DEXRAS1) either exacerbate the circadian phenotypes observed in SMS patients with deletions or increase their penetrance in certain environments. This study also confirms a previous report of abnormal circadian function in Dexras1(-/-) mice. Copyright © 2013 Wiley Periodicals, Inc.

Mitotic Defects Lead to Pervasive Aneuploidy and Accompany Loss of RB1 Activity in Mouse LmnaDhe Dermal Fibroblasts

PubMed Central

Pratt, C. Herbert; Curtain, Michelle; Donahue, Leah Rae; Shopland, Lindsay S.

2011-01-01

Background Lamin A (LMNA) is a component of the nuclear lamina and is mutated in several human diseases, including Emery-Dreifuss muscular dystrophy (EDMD; OMIM ID# 181350) and the premature aging syndrome Hutchinson-Gilford progeria syndrome (HGPS; OMIM ID# 176670). Cells from progeria patients exhibit cell cycle defects in both interphase and mitosis. Mouse models with loss of LMNA function have reduced Retinoblastoma protein (RB1) activity, leading to aberrant cell cycle control in interphase, but how mitosis is affected by LMNA is not well understood. Results We examined the cell cycle and structural phenotypes of cells from mice with the Lmna allele, Disheveled hair and ears (LmnaDhe). We found that dermal fibroblasts from heterozygous LmnaDhe (LmnaDhe/+) mice exhibit many phenotypes of human laminopathy cells. These include severe perturbations to the nuclear shape and lamina, increased DNA damage, and slow growth rates due to mitotic delay. Interestingly, LmnaDhe/+ fibroblasts also had reduced levels of hypophosphorylated RB1 and the non-SMC condensin II-subunit D3 (NCAP-D3), a mitosis specific centromere condensin subunit that depends on RB1 activity. Mitotic check point control by mitotic arrest deficient-like 1 (MAD2L1) also was perturbed in LmnaDhe /+ cells. LmnaDhe /+ fibroblasts were consistently aneuploid and had higher levels of micronuclei and anaphase bridges than normal fibroblasts, consistent with chromosome segregation defects. Conclusions These data indicate that RB1 may be a key regulator of cellular phenotype in laminopathy-related cells, and suggest that the effects of LMNA on RB1 include both interphase and mitotic cell cycle control. PMID:21464947

Wenxin Keli for atrial fibrillation

PubMed Central

He, Zhuogen; Zheng, Minan; Xie, Pingchang; Wang, Yuanping; Yan, Xia; Deng, Dingwei

2018-01-01

Abstract Background: Atrial fibrillation (AF) is a most common cardiac arrhythmia in clinical practice. In China, Wenxin Keli (WXKL) therapy is a common treatment for AF, but its effects and safety remain uncertain. This protocol is to provide the methods used to assess the effectiveness and safety of WXKL for the treatment of patients with AF. Methods: We will search comprehensively the 4 English databases EMBASE, the Cochrane Central Register of Controlled Trials (Cochrane Library), PubMed, and Medline and 3 Chinese databases China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Chinese Science and Technology Periodical database (VIP) on computer on March 2018 for the randomized controlled trials (RCTs) regarding WXKL for AF. The therapeutic effects according to the sinus rhythm and p-wave dispersion (Pwd) will be accepted as the primary outcomes. We will use RevMan V.5.3 software as well to compute the data synthesis carefully when a meta-analysis is allowed. Results: This study will provide a high-quality synthesis of current evidence of WXKL for AF. Conclusion: The conclusion of our systematic review will provide evidence to judge whether WXKL is an effective intervention for patient with AF. PROSPERO registration number: PROSPERO CRD 42018082045. PMID:29702984

A Survey of Data-Base Information Systems Relevant to Navy Requirements Planning

DTIC Science & Technology

1983-02-01

SHIPS \\ AK (FEM) T-AK (FEM) AKD/T-AKO _" ’ AKL/T-AKL AKM MULTIPURPOSE CAR 0 SHI’’S AKR VEHICLE CARGO SHIPS . -■, AK3 ANL AO OILER AC • NEW...the most demanding condition of operation for which a ship must be manned. ( a ) At sea in wartime. (b) Capable of performing all offensive... ship , and aircraft) researchers and others could quickly obtain basic information. 3. The Navy currently maintains a number of related

Enabling Civilian Low-Altitude Airspace and Unmanned Aerial System (UAS) Operations

NASA Technical Reports Server (NTRS)

Kopardekar, Parimal

2014-01-01

UAS operations will be safer if a UTM system is available to support the functions associated with Airspace management and geo-fencing (reduce risk of accidents, impact to other operations, and community concerns); Weather and severe wind integration (avoid severe weather areas based on prediction); Predict and manage congestion (mission safety);Terrain and man-made objects database and avoidance; Maintain safe separation (mission safety and assurance of other assets); Allow only authenticated operations (avoid unauthorized airspace use).

Tools for improving safety management in the Norwegian Fishing Fleet occupational accidents analysis period of 1998-2006.

PubMed

Aasjord, Halvard L

2006-01-01

Reporting of human accidents in the Norwegian Fishing Fleet has always been very difficult because there has been no tradition in making reports on all types of working accidents among fishermen, if the accident does not seem to be very serious or there is no economical incentive to report. Therefore reports are only written when the accidents are serious or if the fisherman is reported sick. Reports about an accident are sent to the insurance company, but another report should also be sent to the Norwegian Maritime Directorate (NMD). Comparing of data from one former insurance company and NMD shows that the real numbers of injuries or serious accidents among Norwegian fishermen could be up to two times more than the numbers reported to NMD. Special analyses of 1690 accidents from the so called PUS-database (NMD) for the period 1998-2002, show that the calculated risk was 23.6 accidents per 1000 man-years. This is quite a high risk level, and most of the accidents in the fishing fleet were rather serious. The calculated risks are highest for fishermen on board the deep sea fleet of trawlers (28.6 accidents per 1000 man-years) and also on the deep sea fleet of purse seiners (28.9 accidents per 1000 man-years). Fatal accidents over a longer period of 51.5 years from 1955 to 2006 are also roughly analysed. These data from SINTEF's own database show that the numbers of fatal accidents have been decreasing over this long period, except for the two periods 1980-84 and 1990-94 where we had some casualties with total losses of larger vessels with the loss of most of the crew, but also many others typical work accidents on smaller vessels. The total numbers of registered Norwegian fishermen and also the numbers of man-years have been drastically reduced over the 51.5 years from 1955 to 2006. The risks of fatal accidents have been very steady over time at a high level, although there has been a marked risk reduction since 1990-94. For the last 8.5-year period of January 1998-July 2006 the numbers of fatal accidents and calculated risks are analysed for three main fleet groups. The highest risk factor of 24.8 fatal accidents per 10.000 man years is found in the smaller fleet, length of vessel (Loa) < 13 meters. This is 4.1 times higher than in the medium fleet (13 < Loa < 28 meters) and 11.3 times higher risk factor than in the deep sea fleet (Loa > 28 meter).

Pyle metaphyseal dysplasia in an African child: Case report and review of the literature.

PubMed

Wonkam, A; Makubalo, N; Roberts, T; Chetty, M

2016-05-25

Pyle disease (OMIM 265900), also known as metaphyseal dysplasia, is a rare autosomal recessive disorder with no known gene mutation. We report a case of Pyle disease in a 7-year-old African boy of mixed ancestry who presented with finger and wrist fractures following minor trauma. The radiological findings revealed abnormally broad metaphyses of the tubular bones, known as Erlenmeyer-flask bone deformity, and mild cranial sclerosis, both hallmarks of the condition. We report the first case in a patient with African ancestry, which could help in the gene discovery of this rare autosomal recessive skeletal dysplasia with unknown mutations.

NASA Video Catalog. Supplement 12

NASA Technical Reports Server (NTRS)

2002-01-01

This report lists 1878 video productions from the NASA STI Database. This issue of the NASA Video Catalog cites video productions listed in the NASA STI Database. The videos listed have been developed by the NASA centers, covering Shuttle mission press conferences; fly-bys of planets; aircraft design, testing and performance; environmental pollution; lunar and planetary exploration; and many other categories related to manned and unmanned space exploration. Each entry in the publication consists of a standard bibliographic citation accompanied by an abstract. The listing of the entries is arranged by STAR categories. A complete Table of Contents describes the scope of each category. For users with specific information, a Title Index is available. A Subject Term Index, based on the NASA Thesaurus, is also included. Guidelines for usage of NASA audio/visual material, ordering information, and order forms are also available.

Modular biometric system

NASA Astrophysics Data System (ADS)

Hsu, Charles; Viazanko, Michael; O'Looney, Jimmy; Szu, Harold

2009-04-01

Modularity Biometric System (MBS) is an approach to support AiTR of the cooperated and/or non-cooperated standoff biometric in an area persistent surveillance. Advanced active and passive EOIR and RF sensor suite is not considered here. Neither will we consider the ROC, PD vs. FAR, versus the standoff POT in this paper. Our goal is to catch the "most wanted (MW)" two dozens, separately furthermore ad hoc woman MW class from man MW class, given their archrivals sparse front face data basis, by means of various new instantaneous input called probing faces. We present an advanced algorithm: mini-Max classifier, a sparse sample realization of Cramer-Rao Fisher bound of the Maximum Likelihood classifier that minimize the dispersions among the same woman classes and maximize the separation among different man-woman classes, based on the simple feature space of MIT Petland eigen-faces. The original aspect consists of a modular structured design approach at the system-level with multi-level architectures, multiple computing paradigms, and adaptable/evolvable techniques to allow for achieving a scalable structure in terms of biometric algorithms, identification quality, sensors, database complexity, database integration, and component heterogenity. MBS consist of a number of biometric technologies including fingerprints, vein maps, voice and face recognitions with innovative DSP algorithm, and their hardware implementations such as using Field Programmable Gate arrays (FPGAs). Biometric technologies and the composed modularity biometric system are significant for governmental agencies, enterprises, banks and all other organizations to protect people or control access to critical resources.

Use of artificial intelligence to analyze clinical database reduces workload on surgical house staff.

PubMed

Grossi, E A; Steinberg, B M; LeBoutillier, M; Coppa, G F; Roses, D F

1994-08-01

The current quantity and diversity of hospital clinical, laboratory, and pharmacy records have resulted in a glut of information, which can be overwhelming to house staff. This study was performed to measure the impact of artificial intelligence analysis of such data on the junior surgical house staff's workload, time for direct patient care, and quality of life. A personal computer was interfaced with the hospital computerized patient data system. Artificial intelligence algorithms were applied to retrieve and condense laboratory values, microbiology reports, and medication orders. Unusual laboratory tests were reported without artificial intelligence filtering. A survey of 23 junior house staff showed a requirement for a total of 30.75 man-hours per day, an average of 184.5 minutes per service twice a day for five surgical services each with an average of 40.7 patients, to manually produce a report in contrast to a total of 3.4 man-hours, an average of 20.5 minutes on the same basis (88.9% reduction, p < 0.001), to computer generate and distribute a similarly useful report. Two thirds of the residents reported an increased ability to perform patient care. Current medical practice has created an explosion of information, which is a burden for surgical house staff. Artificial intelligence preprocessing of the hospital database information focuses attention, eliminates superfluous data, and significantly reduces surgical house staff clerical work, allowing more time for education, research, and patient care.

eCOMPAGT – efficient Combination and Management of Phenotypes and Genotypes for Genetic Epidemiology

PubMed Central

Schönherr, Sebastian; Weißensteiner, Hansi; Coassin, Stefan; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

2009-01-01

Background High-throughput genotyping and phenotyping projects of large epidemiological study populations require sophisticated laboratory information management systems. Most epidemiological studies include subject-related personal information, which needs to be handled with care by following data privacy protection guidelines. In addition, genotyping core facilities handling cooperative projects require a straightforward solution to monitor the status and financial resources of the different projects. Description We developed a database system for an efficient combination and management of phenotypes and genotypes (eCOMPAGT) deriving from genetic epidemiological studies. eCOMPAGT securely stores and manages genotype and phenotype data and enables different user modes with different rights. Special attention was drawn on the import of data deriving from TaqMan and SNPlex genotyping assays. However, the database solution is adjustable to other genotyping systems by programming additional interfaces. Further important features are the scalability of the database and an export interface to statistical software. Conclusion eCOMPAGT can store, administer and connect phenotype data with all kinds of genotype data and is available as a downloadable version at . PMID:19432954

Breviscapine Injection Improves the Therapeutic Effect of Western Medicine on Angina Pectoris Patients.

PubMed

Wang, Chuan; Li, Yafeng; Gao, Shoucui; Cheng, Daxin; Zhao, Sihai; Liu, Enqi

2015-01-01

To evaluate the beneficial and adverse effects of breviscapine injection in combination with Western medicine on the treatment of patients with angina pectoris. The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, the China National Knowledge Infrastructure, the Wanfang Database, the Chongqing VIP Information Database and the China Biomedical Database were searched to identify randomized clinical trials (RCTs) that evaluated the effects of Western medicine compared to breviscapine injection plus Western medicine on angina pectoris patients. The included studies were analyzed using RevMan 5.1.0 software. The literature search yielded 460 studies, wherein 16 studies matched the selection criteria. The results showed that combined therapy using Breviscapine plus Western medicine was superior to Western medicine alone for improving angina pectoris symptoms (OR=3.77, 95% Cl: 2.76~5.15) and also resulted in increased electrocardiogram (ECG) improvement (OR=2.77, 95% Cl: 2.16~3.53). The current evidence suggests that Breviscapine plus Western medicine achieved a superior therapeutic effect compared to Western medicine alone.

Breviscapine Injection Improves the Therapeutic Effect of Western Medicine on Angina Pectoris Patients

PubMed Central

Wang, Chuan; Li, Yafeng; Gao, Shoucui; Cheng, Daxin; Zhao, Sihai; Liu, Enqi

2015-01-01

To evaluate the beneficial and adverse effects of breviscapine injection in combination with Western medicine on the treatment of patients with angina pectoris. The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, the China National Knowledge Infrastructure, the Wanfang Database, the Chongqing VIP Information Database and the China Biomedical Database were searched to identify randomized clinical trials (RCTs) that evaluated the effects of Western medicine compared to breviscapine injection plus Western medicine on angina pectoris patients. The included studies were analyzed using RevMan 5.1.0 software. The literature search yielded 460 studies, wherein 16 studies matched the selection criteria. The results showed that combined therapy using Breviscapine plus Western medicine was superior to Western medicine alone for improving angina pectoris symptoms (OR =3.77, 95% Cl: 2.76~5.15) and also resulted in increased electrocardiogram (ECG) improvement (OR=2.77, 95% Cl: 2.16~3.53). The current evidence suggests that Breviscapine plus Western medicine achieved a superior therapeutic effect compared to Western medicine alone. PMID:26052709

A subjective study and an objective metric to quantify the granularity level of textures

NASA Astrophysics Data System (ADS)

Subedar, Mahesh M.; Karam, Lina J.

2015-03-01

Texture granularity is an important visual characteristic that is useful in a variety of applications, including analysis, recognition, and compression, to name a few. A texture granularity measure can be used to quantify the perceived level of texture granularity. The granularity level of the textures is influenced by the size of the texture primitives. A primitive is defined as the smallest recognizable repetitive object in the texture. If the texture has large primitives then the perceived granularity level tends to be lower as compared to a texture with smaller primitives. In this work we are presenting a texture granularity database referred as GranTEX which consists of 30 textures with varying levels of primitive sizes and granularity levels. The GranTEX database consists of both natural and man-made textures. A subjective study is conducted to measure the perceived granularity level of textures present in the GranTEX database. An objective metric that automatically measures the perceived granularity level of textures is also presented as part of this work. It is shown that the proposed granularity metric correlates well with the subjective granularity scores.

Comparison of constitutive flow resistance equations based on the Manning and Chezy equations applied to natural rivers

USGS Publications Warehouse

Bjerklie, David M.; Dingman, S. Lawrence; Bolster, Carl H.

2005-01-01

A set of conceptually derived in‐bank river discharge–estimating equations (models), based on the Manning and Chezy equations, are calibrated and validated using a database of 1037 discharge measurements in 103 rivers in the United States and New Zealand. The models are compared to a multiple regression model derived from the same data. The comparison demonstrates that in natural rivers, using an exponent on the slope variable of 0.33 rather than the traditional value of 0.5 reduces the variance associated with estimating flow resistance. Mean model uncertainty, assuming a constant value for the conductance coefficient, is less than 5% for a large number of estimates, and 67% of the estimates would be accurate within 50%. The models have potential application where site‐specific flow resistance information is not available and can be the basis for (1) a general approach to estimating discharge from remotely sensed hydraulic data, (2) comparison to slope‐area discharge estimates, and (3) large‐scale river modeling.

[Meta-analysis for correlation between multiple lung lobe lesions and prognostic influence on acquired pneumonia in hospitalized elderly patients].

PubMed

Huang, Wenjie; Feng, Wei; Li, Yang; Chen, Yu

2014-11-01

To explore the correlation regarding the prognostic influence between multiple lung lobe lesions and acquired pneumonia in hospitalized elderly patients by a Meta-analysis. We collected all studies which investigated the correlation regarding the prognostic effect between multiple lung lobe lesions and acquired pneumonia by searching China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, Chinese Biological Medical Literature Database, PubMed, and EMBase in accordance with the inclusion and exclusion criteria. Th e retrieval limit time of searches was from databases establishment to July 2014. Th e Meta-analysis was performed by using RevMan5.2 soft ware. We calculated the odds ratio (OR) and 95% confidence interval (95% CI) by using heterogeneous tests. Publication bias was assessed by Egger's test and funnel plot, and the sensitivity was analyzed. Ten studies involving 1 836 patients were finally included, with 487 cases (the dead group) and 1 349 controls (the survival group). The Meta-analysis demonstrated that multiple lung lobe lesions was highly correlated with the prognosis for the aged acquired pneumonia (OR=3.22, 95% CI 1.84 to 5.63). Multiple lung lobe lesions increase the risk of death in the prognosis of the aged patients with acquired pneumonia.

Juvenile Moyamoya and Craniosynostosis in a Child with Deletion 1p32p31: Expanding the Clinical Spectrum of 1p32p31 Deletion Syndrome and a Review of the Literature

PubMed Central

Prontera, Paolo; Rogaia, Daniela; Mencarelli, Amedea; Ottaviani, Valentina; Guercini, Giorgio; Bersano, Anna; Stangoni, Gabriela

2017-01-01

Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterised by the progressive occlusion of the internal carotid artery. Its aetiology is uncertain, but a genetic background seems likely, given the high MA familial rate. To investigate the aetiology of craniosynostosis and juvenile moyamoya in a 14-year-old male patient, we performed an array-comparative genomic hybridisation revealing a de novo interstitial deletion of 8.5 Mb in chromosome region 1p32p31. The deletion involved 34 protein coding genes, including NF1A, whose haploinsufficiency is indicated as being mainly responsible for the 1p32-p31 chromosome deletion syndrome phenotype (OMIM 613735). Our patient also has a deleted FOXD3 of the FOX gene family of transcription factors, which plays an important role in neural crest cell growth and differentiation. As the murine FOXD3−/− model shows craniofacial anomalies and abnormal common carotid artery morphology, it can be hypothesised that FOXD3 is involved in the pathogenesis of the craniofacial and vascular defects observed in our patient. In support of our assumption, we found in the literature another patient with a syndromic form of MA who had a deletion involving another FOX gene (FOXC1). In addition to describing the clinical history of our patient, we have reviewed all of the available literature concerning other patients with a 1p32p31 deletion, including cases from the Decipher database, and we have also reviewed the genetic disorders associated with MA, which is a useful guide for the diagnosis of syndromic form of MA. PMID:28926972

Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta 4 integrin gene (ITGB4) and genotype/phenotype correlations.

PubMed

Nakano, A; Pulkkinen, L; Murrell, D; Rico, J; Lucky, A W; Garzon, M; Stevens, C A; Robertson, S; Pfendner, E; Uitto, J

2001-05-01

Epidermolysis bullosa with pyloric atresia (EB-PA: OMIM 226730), also known as Carmi syndrome, is a rare autosomal recessive genodermatosis that manifests with neonatal mucocutaneous fragility associated with congenital pyloric atresia. The disease is frequently lethal within the first year, but nonlethal cases have been reported. Mutations in the genes encoding subunit polypeptides of the alpha 6 beta 4 integrin (ITGA6 and ITGB4) have been demonstrated in EB-PA patients. To extend the repertoire of mutations and to identify genotype-phenotype correlations, we examined seven new EB-PA families, four with lethal and three with nonlethal disease variants. DNA from patients was screened for mutations using heteroduplex analysis followed by nucleotide sequencing of PCR products spanning all beta 4 integrin-coding sequences. Mutation analysis disclosed 12 distinct mutations, 11 of them novel. Four mutations predicted a premature termination codon as a result of nonsense mutations or small out-of-frame insertions or deletions, whereas seven were missense mutations. This brings the total number of distinct ITGB4 mutations to 33. The mutation database indicates that premature termination codons are associated predominantly with the lethal EB-PA variants, whereas missense mutations are more prevalent in nonlethal forms. However, the consequences of the missense mutations are position dependent, and substitutions of highly conserved amino acids may have lethal consequences. In general, indirect immunofluorescence studies of affected skin revealed negative staining for beta 4 integrin in lethal cases and positive, but attenuated, staining in nonlethal cases and correlated with clinical phenotype. The data on specific mutations in EB-PA patients allows prenatal testing and preimplantation genetic diagnosis in families at risk.

Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.

PubMed

Tabor, Holly K; Auer, Paul L; Jamal, Seema M; Chong, Jessica X; Yu, Joon-Ho; Gordon, Adam S; Graubert, Timothy A; O'Donnell, Christopher J; Rich, Stephen S; Nickerson, Deborah A; Bamshad, Michael J

2014-08-07

Exome sequencing (ES) is rapidly being deployed for use in clinical settings despite limited empirical data about the number and types of incidental results (with potential clinical utility) that could be offered for return to an individual. We analyzed deidentified ES data from 6,517 participants (2,204 African Americans and 4,313 European Americans) from the National Heart, Lung, and Blood Institute Exome Sequencing Project. We characterized the frequencies of pathogenic alleles in genes underlying Mendelian conditions commonly assessed by newborn-screening (NBS, n = 39) programs, genes associated with age-related macular degeneration (ARMD, n = 17), and genes known to influence drug response (PGx, n = 14). From these 70 genes, we identified 10,789 variants and curated them by manual review of OMIM, HGMD, locus-specific databases, or primary literature to a total of 399 validated pathogenic variants. The mean number of risk alleles per individual was 15.3. Every individual had at least five known PGx alleles, 99% of individuals had at least one ARMD risk allele, and 45% of individuals were carriers for at least one pathogenic NBS allele. The carrier burden for severe recessive childhood disorders was 0.57. Our results demonstrate that risk alleles of potential clinical utility for both Mendelian and complex traits are detectable in every individual. These findings highlight the necessity of developing guidelines and policies that consider the return of results to all individuals and underscore the need to develop innovative approaches and tools that enable individuals to exercise their choice about the return of incidental results. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Meta-analysis diagnostic accuracy of SNP-based pathogenicity detection tools: a case of UTG1A1 gene mutations.

PubMed

Galehdari, Hamid; Saki, Najmaldin; Mohammadi-Asl, Javad; Rahim, Fakher

2013-01-01

Crigler-Najjar syndrome (CNS) type I and type II are usually inherited as autosomal recessive conditions that result from mutations in the UGT1A1 gene. The main objective of the present review is to summarize results of all available evidence on the accuracy of SNP-based pathogenicity detection tools compared to published clinical result for the prediction of in nsSNPs that leads to disease using prediction performance method. A comprehensive search was performed to find all mutations related to CNS. Database searches included dbSNP, SNPdbe, HGMD, Swissvar, ensemble, and OMIM. All the mutation related to CNS was extracted. The pathogenicity prediction was done using SNP-based pathogenicity detection tools include SIFT, PHD-SNP, PolyPhen2, fathmm, Provean, and Mutpred. Overall, 59 different SNPs related to missense mutations in the UGT1A1 gene, were reviewed. Comparing the diagnostic OR, PolyPhen2 and Mutpred have the highest detection 4.983 (95% CI: 1.24 - 20.02) in both, following by SIFT (diagnostic OR: 3.25, 95% CI: 1.07 - 9.83). The highest MCC of SNP-based pathogenicity detection tools, was belong to SIFT (34.19%) followed by Provean, PolyPhen2, and Mutpred (29.99%, 29.89%, and 29.89%, respectively). Hence the highest SNP-based pathogenicity detection tools ACC, was fit to SIFT (62.71%) followed by PolyPhen2, and Mutpred (61.02%, in both). Our results suggest that some of the well-established SNP-based pathogenicity detection tools can appropriately reflect the role of a disease-associated SNP in both local and global structures.

BioTextQuest(+): a knowledge integration platform for literature mining and concept discovery.

PubMed

Papanikolaou, Nikolas; Pavlopoulos, Georgios A; Pafilis, Evangelos; Theodosiou, Theodosios; Schneider, Reinhard; Satagopam, Venkata P; Ouzounis, Christos A; Eliopoulos, Aristides G; Promponas, Vasilis J; Iliopoulos, Ioannis

2014-11-15

The iterative process of finding relevant information in biomedical literature and performing bioinformatics analyses might result in an endless loop for an inexperienced user, considering the exponential growth of scientific corpora and the plethora of tools designed to mine PubMed(®) and related biological databases. Herein, we describe BioTextQuest(+), a web-based interactive knowledge exploration platform with significant advances to its predecessor (BioTextQuest), aiming to bridge processes such as bioentity recognition, functional annotation, document clustering and data integration towards literature mining and concept discovery. BioTextQuest(+) enables PubMed and OMIM querying, retrieval of abstracts related to a targeted request and optimal detection of genes, proteins, molecular functions, pathways and biological processes within the retrieved documents. The front-end interface facilitates the browsing of document clustering per subject, the analysis of term co-occurrence, the generation of tag clouds containing highly represented terms per cluster and at-a-glance popup windows with information about relevant genes and proteins. Moreover, to support experimental research, BioTextQuest(+) addresses integration of its primary functionality with biological repositories and software tools able to deliver further bioinformatics services. The Google-like interface extends beyond simple use by offering a range of advanced parameterization for expert users. We demonstrate the functionality of BioTextQuest(+) through several exemplary research scenarios including author disambiguation, functional term enrichment, knowledge acquisition and concept discovery linking major human diseases, such as obesity and ageing. The service is accessible at http://bioinformatics.med.uoc.gr/biotextquest. g.pavlopoulos@gmail.com or georgios.pavlopoulos@esat.kuleuven.be Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

What is new in genetics and osteogenesis imperfecta classification?

PubMed

Valadares, Eugênia R; Carneiro, Túlio B; Santos, Paula M; Oliveira, Ana Cristina; Zabel, Bernhard

2014-01-01

Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. Literature review in the PubMed and OMIM databases, followed by selection of relevant references. In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

PCR Amplicon Prediction from Multiplex Degenerate Primer and Probe Sets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, S. N.

2013-08-08

Assessing primer specificity and predicting both desired and off-target amplification products is an essential step for robust PCR assay design. Code is described to predict potential polymerase chain reaction (PCR) amplicons in a large sequence database such as NCBI nt from either singleplex or a large multiplexed set of primers, allowing degenerate primer and probe bases, with target mismatch annotates amplicons with gene information automatically downloaded from NCBI, and optionally it can predict whether there are also TaqMan/Luminex probe matches within predicted amplicons.

[Effect of 3D printing technology on pelvic fractures:a Meta-analysis].

PubMed

Zhang, Yu-Dong; Wu, Ren-Yuan; Xie, Ding-Ding; Zhang, Lei; He, Yi; Zhang, Hong

2018-05-25

To evaluate the effect of 3D printing technology applied in the surgical treatment of pelvic fractures through the published literatures by Meta-analysis. The PubMed database, EMCC database, CBM database, CNKI database, VIP database and Wanfang database were searched from the date of database foundation to August 2017 to collect the controlled clinical trials in wich 3D printing technology was applied in preoperative planning of pelvic fracture surgery. The retrieved literatures were screened according to predefined inclusion and exclusion criteria, and quality evaluation were performed. Then, the available data were extracted and analyzed with the RevMan5.3 software. Totally 9 controlled clinical trials including 638 cases were chosen. Among them, 279 cases were assigned to the 3D printing technology group and 359 cases to the conventional group. The Meta-analysis results showed that the operative time[SMD=-2.81, 95%CI(-3.76, -1.85)], intraoperative blood loss[SMD=-3.28, 95%CI(-4.72, -1.85)] and the rate of complication [OR=0.47, 95%CI(0.25, 0.87)] in the 3D printing technology were all lower than those in the conventional group;the excellent and good rate of pelvic fracture reduction[OR=2.09, 95%CI(1.32, 3.30)] and postoperative pelvic functional restoration [OR=1.94, 95%CI(1.15, 3.28) in the 3D printing technology were all superior to those in the conventional group. 3D printing technology applied in the surgical treatment of pelvic fractures has the advantage of shorter operative time, less intraoperative blood loss and lower rate of complication, and can improve the quality of pelvic fracture reduction and the recovery of postoperative pelvic function. Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.

Human spaceflight technology needs-a foundation for JSC's technology strategy

NASA Astrophysics Data System (ADS)

Stecklein, J. M.

Human space exploration has always been heavily influenced by goals to achieve a specific mission on a specific schedule. This approach drove rapid technology development, the rapidity of which added risks and became a major driver for costs and cost uncertainty. The National Aeronautics and Space Administration (NASA) is now approaching the extension of human presence throughout the solar system by balancing a proactive yet less schedule-driven development of technology with opportunistic scheduling of missions as the needed technologies are realized. This approach should provide cost effective, low risk technology development that will enable efficient and effective manned spaceflight missions. As a first step, the NASA Human Spaceflight Architecture Team (HAT) has identified a suite of critical technologies needed to support future manned missions across a range of destinations, including in cis-lunar space, near earth asteroid visits, lunar exploration, Mars moons, and Mars exploration. The challenge now is to develop a strategy and plan for technology development that efficiently enables these missions over a reasonable time period, without increasing technology development costs unnecessarily due to schedule pressure, and subsequently mitigating development and mission risks. NASA's Johnson Space Center (JSC), as the nation's primary center for human exploration, is addressing this challenge through an innovative approach in allocating Internal Research and Development funding to projects. The HAT Technology Needs (Tech Needs) Database has been developed to correlate across critical technologies and the NASA Office of Chief Technologist Technology Area Breakdown Structure (TABS). The TechNeeds Database illuminates that many critical technologies may support a single technical capability gap, that many HAT technology needs may map to a single TABS technology discipline, and that a single HAT technology need may map to multiple TABS technology disciplines. Th- TechNeeds Database greatly clarifies understanding of the complex relationships of critical technologies to mission and architecture element needs. Extensions to the core TechNeeds Database allow JSC to factor in and appropriately weight JSC core technology competencies, and considerations of commercialization potential and partnership potential. The inherent coupling among these, along with an appropriate importance weighting, has provided an initial prioritization for allocation of technology development research funding at JSc. The HAT Technology Needs Database, with a core of built-in reports, clarifies and communicates complex technology needs for cost effective human space exploration so that an organization seeking to assure that research prioritization supports human spaceflight of the future can be successful.

Human Spaceflight Technology Needs - A Foundation for JSC's Technology Strategy

NASA Technical Reports Server (NTRS)

Stecklein, Jonette M.

2013-01-01

Human space exploration has always been heavily influenced by goals to achieve a specific mission on a specific schedule. This approach drove rapid technology development, the rapidity of which adds risks as well as provides a major driver for costs and cost uncertainty. The National Aeronautics and Space Administration (NASA) is now approaching the extension of human presence throughout the solar system by balancing a proactive yet less schedule-driven development of technology with opportunistic scheduling of missions as the needed technologies are realized. This approach should provide cost effective, low risk technology development that will enable efficient and effective manned spaceflight missions. As a first step, the NASA Human Spaceflight Architecture Team (HAT) has identified a suite of critical technologies needed to support future manned missions across a range of destinations, including in cis-lunar space, near earth asteroid visits, lunar exploration, Mars moons, and Mars exploration. The challenge now is to develop a strategy and plan for technology development that efficiently enables these missions over a reasonable time period, without increasing technology development costs unnecessarily due to schedule pressure, and subsequently mitigating development and mission risks. NASA's Johnson Space Center (JSC), as the nation s primary center for human exploration, is addressing this challenge through an innovative approach in allocating Internal Research and Development funding to projects. The HAT Technology Needs (TechNeeds) Database has been developed to correlate across critical technologies and the NASA Office of Chief Technologist Technology Area Breakdown Structure (TABS). The TechNeeds Database illuminates that many critical technologies may support a single technical capability gap, that many HAT technology needs may map to a single TABS technology discipline, and that a single HAT technology need may map to multiple TABS technology disciplines. The TechNeeds Database greatly clarifies understanding of the complex relationships of critical technologies to mission and architecture element needs. Extensions to the core TechNeeds Database allow JSC to factor in and appropriately weight JSC Center Core Technology Competencies, and considerations of Commercialization Potential and Partnership Potential. The inherent coupling among these, along with an appropriate importance weighting, has provided an initial prioritization for allocation of technology development research funding for JSC. The HAT Technology Needs Database, with a core of built-in reports, clarifies and communicates complex technology needs for cost effective human space exploration such that an organization seeking to assure that research prioritization supports human spaceflight of the future can be successful.

CELL5M: A geospatial database of agricultural indicators for Africa South of the Sahara.

PubMed

Koo, Jawoo; Cox, Cindy M; Bacou, Melanie; Azzarri, Carlo; Guo, Zhe; Wood-Sichra, Ulrike; Gong, Queenie; You, Liangzhi

2016-01-01

Recent progress in large-scale georeferenced data collection is widening opportunities for combining multi-disciplinary datasets from biophysical to socioeconomic domains, advancing our analytical and modeling capacity. Granular spatial datasets provide critical information necessary for decision makers to identify target areas, assess baseline conditions, prioritize investment options, set goals and targets and monitor impacts. However, key challenges in reconciling data across themes, scales and borders restrict our capacity to produce global and regional maps and time series. This paper provides overview, structure and coverage of CELL5M-an open-access database of geospatial indicators at 5 arc-minute grid resolution-and introduces a range of analytical applications and case-uses. CELL5M covers a wide set of agriculture-relevant domains for all countries in Africa South of the Sahara and supports our understanding of multi-dimensional spatial variability inherent in farming landscapes throughout the region.

Systematic review on randomized controlled clinical trials of acupuncture therapy for neurovascular headache.

PubMed

Zhao, Lei; Guo, Yi; Wang, Wei; Yan, Li-juan

2011-08-01

To evaluate the effectiveness of acupuncture as a treatment for neurovascular headache and to analyze the current situation related to acupuncture treatment. PubMed database (1966-2010), EMBASE database (1986-2010), Cochrane Library (Issue 1, 2010), Chinese Biomedical Literature Database (1979-2010), China HowNet Knowledge Database (1979-2010), VIP Journals Database (1989-2010), and Wanfang database (1998-2010) were retrieved. Randomized or quasi-randomized controlled studies were included. The priority was given to high-quality randomized, controlled trials. Statistical outcome indicators were measured using RevMan 5.0.20 software. A total of 16 articles and 1 535 cases were included. Meta-analysis showed a significant difference between the acupuncture therapy and Western medicine therapy [combined RR (random efficacy model)=1.46, 95% CI (1.21, 1.75), Z=3.96, P<0.0001], indicating an obvious superior effect of the acupuncture therapy; significant difference also existed between the comprehensive acupuncture therapy and acupuncture therapy alone [combined RR (fixed efficacy model)=3.35, 95% CI (1.92, 5.82), Z=4.28, P<0.0001], indicating that acupuncture combined with other therapies, such as points injection, scalp acupuncture, auricular acupuncture, etc., were superior to the conventional body acupuncture therapy alone. The inclusion of limited clinical studies had verified the efficacy of acupuncture in the treatment of neurovascular headache. Although acupuncture or its combined therapies provides certain advantages, most clinical studies are of small sample sizes. Large sample size, randomized, controlled trials are needed in the future for more definitive results.

Simulating the effect of ignition source type on forest fire statistics

NASA Astrophysics Data System (ADS)

Krenn, Roland; Hergarten, Stefan

2010-05-01

Forest fires belong to the most frightening natural hazards, and have long-term ecological and economic effects on the regions involved. It was found that their frequency-area distributions show power-law behaviour under a wide variety of conditions, interpreting them as a self-organised critical phenomenon. Using computer simulations, self-organised critical behaviour manifests in simple cellular automaton models. With respect to ignition source, forest fires can be categorised as lightning-induced or as a result of human activity. Lightning fires are considered to be natural, whereas ``man made'' fires are frequently caused by some sort of technological disaster, such as sparks from wheels of trains, the rupture of overhead electrical lines, the misuse of electrical or mechanical devices and so on. Taking into account that such events rarely occur deep in the woods, man made fires should start preferably on the edge of a forest or where the forest is not very dense. We present a modification in the self-organised critical Drossel-Schwabl forest fire model that takes these two different triggering mechanisms into account and increases the scaling exponent of the frequency-area distribution by ca. 1/3. Combined simulations further predict a dependence of the overall event-size distribution on the ratio of lightning-induced and man made fires as well as a splitting of their partial distributions. Lightning is identified as the dominant mechanism in the regime of the largest fires. The results are confirmed by the analysis of the Canadian Large Fire Database and suggest that lightning-induced and man made forest fires cannot be treated separately in wildfire modelling, hazard assessment and forest management.

Simulating statistics of lightning-induced and man made fires

NASA Astrophysics Data System (ADS)

Krenn, R.; Hergarten, S.

2009-04-01

The frequency-area distributions of forest fires show power-law behavior with scaling exponents α in a quite narrow range, relating wildfire research to the theoretical framework of self-organized criticality. Examples of self-organized critical behavior can be found in computer simulations of simple cellular automata. The established self-organized critical Drossel-Schwabl forest fire model (DS-FFM) is one of the most widespread models in this context. Despite its qualitative agreement with event-size statistics from nature, its applicability is still questioned. Apart from general concerns that the DS-FFM apparently oversimplifies the complex nature of forest dynamics, it significantly overestimates the frequency of large fires. We present a straightforward modification of the model rules that increases the scaling exponent α by approximately 1•3 and brings the simulated event-size statistics close to those observed in nature. In addition, combined simulations of both the original and the modified model predict a dependence of the overall distribution on the ratio of lightning induced and man made fires as well as a difference between their respective event-size statistics. The increase of the scaling exponent with decreasing lightning probability as well as the splitting of the partial distributions are confirmed by the analysis of the Canadian Large Fire Database. As a consequence, lightning induced and man made forest fires cannot be treated separately in wildfire modeling, hazard assessment and forest management.

A network medicine approach to quantify distance between hereditary disease modules on the interactome

NASA Astrophysics Data System (ADS)

Caniza, Horacio; Romero, Alfonso E.; Paccanaro, Alberto

2015-12-01

We introduce a MeSH-based method that accurately quantifies similarity between heritable diseases at molecular level. This method effectively brings together the existing information about diseases that is scattered across the vast corpus of biomedical literature. We prove that sets of MeSH terms provide a highly descriptive representation of heritable disease and that the structure of MeSH provides a natural way of combining individual MeSH vocabularies. We show that our measure can be used effectively in the prediction of candidate disease genes. We developed a web application to query more than 28.5 million relationships between 7,574 hereditary diseases (96% of OMIM) based on our similarity measure.

Ionic liquids toxicity on fresh water microalgae, Scenedesmus quadricauda, Chlorella vulgaris &Botryococcus braunii; selection criterion for use in a two-phase partitioning bioreactor (TPPBR).

PubMed

Quraishi, Khurrum Shehzad; Bustam, Mohamad Azmi; Krishnan, Sooridarsan; Aminuddin, Noor Fathanah; Azeezah, Noraisyah; Ghani, Noraini Abd; Uemura, Yoshimitsu; Lévêque, Jean Marc

2017-10-01

A promising method of Carbon dioxide (CO 2 ) valorization is to use green microalgae photosynthesis to process biofuel. Two Phase Partitioning Bioreactors (TPPBR) offer the possibility to use non-aqueous phase liquids (NAPL) to enhance CO 2 solubility; thus making CO 2 available to maximize algae growth. This requires relatively less toxic hydrophobic Ionic Liquids (ILs) that comprise a new class of ionic compounds with remarkable physicochemical properties and thus qualifies them as NAPL candidates. This paper concerns the synthesis of ILs with octyl and butyl chains as well as different cations containing aromatic (imidazolium, pyridinium) and non-aromatic (piperidinum, pyrrolidinium) rings for CO 2 absorption studies. The authors measured their respective toxicity levels on microalgae species, specifically, Scenedesmus quadricauda, Chlorella vulgaris and Botryococcus braunii. Results revealed that octyl-based ILs were more toxic than butyl-based analogues. Such was the case for bmim-PF6 at double saturation with an absorbance of 0.11, compared to Omim-PF6 at 0.17, bmim-NTf2 at 0.02, and Omim-NTf2 at 0.14, respectively. CO 2 uptake results for ILs bearing octyl-based chains compared to the butyl analog were 54% (nCO 2 /nIL) (i.e., moles of CO 2 moles of IL) and 38% (nCO 2 /nIL), respectively. Conclusively, 1-butyl-1-methylpiperidinium absorbed 13% (nCO 2 /nIL) and appeared the least toxic, having an absorbance of 0.25 at 688 nm (double saturation at 7 d) compared to 1-butyl-3-methylimidazolium, which showed the highest toxicity with zero absorbance. Accordingly, these findings suggest that 1-butyl-1-methylpiperidinium is capable of transporting CO 2 to a system containing green microalgae without causing significant harm; thus allowing its use in TPPBR technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.

PubMed

Jiang, Li; Edwards, Stefan M; Thomsen, Bo; Workman, Christopher T; Guldbrandtsen, Bernt; Sørensen, Peter

2014-09-24

Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization. We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data from genome-wide association studies, and will help in the understanding of how the associated genetic variants influence disease or quantitative phenotypes.

Subtelomeric Deletion of Chromosome 10p15.3: Clinical Findings and Molecular Cytogenetic Characterization

PubMed Central

DeScipio, Cheryl; Conlin, Laura; Rosenfeld, Jill; Tepperberg, James; Pasion, Romela; Patel, Ankita; McDonald, Marie T; Aradhya, Swaroop; Ho, Darlene; Goldstein, Jennifer; McGuire, Marianne; Mulchandani, Surabhi; Medne, Livija; Rupps, Rosemarie; Serrano, Alvaro H.; Thorland, Erik C; Tsai, Anne C-H; Hilhorst-Hofstee, Yvonne; Ruivenkamp, Claudia AL; Van Esch, Hilde; Addor, Marie-Claude; Martinet, Danielle; Mason, Thornton B.A.; Clark, Dinah; Spinner, Nancy B; Krantz, Ian D

2012-01-01

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11,), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM# 608668) and DIP2C (OMIM# 611380) (UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study. PMID:22847950

Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization.

PubMed

DeScipio, Cheryl; Conlin, Laura; Rosenfeld, Jill; Tepperberg, James; Pasion, Romela; Patel, Ankita; McDonald, Marie T; Aradhya, Swaroop; Ho, Darlene; Goldstein, Jennifer; McGuire, Marianne; Mulchandani, Surabhi; Medne, Livija; Rupps, Rosemarie; Serrano, Alvaro H; Thorland, Erik C; Tsai, Anne C-H; Hilhorst-Hofstee, Yvonne; Ruivenkamp, Claudia A L; Van Esch, Hilde; Addor, Marie-Claude; Martinet, Danielle; Mason, Thornton B A; Clark, Dinah; Spinner, Nancy B; Krantz, Ian D

2012-09-01

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study. Copyright © 2012 Wiley Periodicals, Inc.

Theoretical and computational studies of renewable energy materials: Room temperature ionic liquids and proton exchange membranes

NASA Astrophysics Data System (ADS)

Feng, Shulu

2011-12-01

Two kinds of renewable energy materials, room temperature ionic liquids (RTILs) and proton exchange membranes (PEMs), especially Nafion, are studied by computational and theoretical approaches. The ultimate purpose of the present research is to design novel materials to meet the future energy demands. To elucidate the effect of alkyl side chain length and anion on the structure and dynamics of the mixtures, molecular dynamics (MD) simulations of three RTILs/water mixtures at various water mole fractions: 1-butyl-3-methylimidazolium (BMIM+)/BF4-, 1-octyl-3-methylimidazolium (OMIM+)/BF4-, and OMIM +/Cl- are performed. Replacing the BMIM + cation with OMIM+ results in stronger aggregation of the cations as well as a slower diffusion of the anions, and replacing the BF4- anion with Cl- alters the water distribution at low water mole fractions and slows diffusion of the mixtures. Potential experimental manifestations of these behaviors in both cases are provided. Proton solvation properties and transport mechanisms are studied in hydrated Nafion, by using the self-consistent multistate empirical valence bond (SCI-MS-EVB) method. It is found that by stabilizing a more Zundel-like (H5O 2+) structure in the first solvation shells, the solvation of excess protons, as well as the proton hydration structure are both influenced by the sulfonate groups. Hydrate proton-related hydrogen bond networks are observed to be more stable than those with water alone. In order to characterize the nature of the proton transport (PT), diffusive motion, Arrhenius activation energies, and transport pathways are calculated and analyzed. Analysis of diffusive motion suggests that (1) a proton-hopping mechanism dominates the proton transport for the studied water loading levels and (2) there is an obvious degree of anti-correlation between the proton hopping and the vehicular transport. The activation energy drops rapidly with an increasing water content when the water loading level is smaller than ˜ 10 H2O/SO 3-, which is consistent with experimental observations. The sulfonate groups are also found to have influence on the proton hopping directions. The temperature and water content effects on the PT pathways are also investigated. The morphological effects on proton solvation and transport in hydrated Nafion are investigated, by using the SCI-MS-EVB method. Two of the most significant morphological models of Nafion, the lamellar model and the cylinder model, are selected. The two models exhibit distinct PT patterns, which result in different proton diffusion rates. In both models, the interaction between protons and the sulfonate groups are proven to be the key to determining PT behavior. The proton solvation structure change as a function of the distance between protons and sulfonate groups has been analyzed. It is found that the increase of water cylinder radius or water layer height leads to the presence of more protons around the sulfonate groups. Furthermore, at a lower hydration level, the increased amount of protons around the sulfonate groups consists of more Zundel-like structures, which is influenced by the distinct morphological structures of Nafion.

Ginkgo Biloba extract for angina pectoris: a systematic review.

PubMed

Sun, Tian; Wang, Xian; Xu, Hao

2015-07-01

To evaluate the efficacy and safety of Ginkgo Biloba extract for patients with angina pectoris according to the available evidence. Electronic databases were searched for all of the randomized controlled trials (RCTs) of angina pectoris treatments with Ginkgo Biloba extract, either alone or combined with routine Western medicine (RWM), and controlled by untreated, placebo, Chinese patent medicine, or RWM treatment. The RCTs were retrieved from the following electronic databases: PubMed/MEDLINE, ProQuest Health and Medical Complete, Springer, Elsevier, and ProQuest Dissertations and Theses, Wanfang Data, China National Knowledge Infrastructure (CNKI), VIP database, China Biology Medicine (CBM), Chinese Medical Citation Index (CMCI), from the earliest database records to December 2012. No language restriction was applied. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. RevMan 5.1.0 provided by Cochrane Collaboration The data were analysed by using. A total of 23 RCTs (involving 2,529 patients) were included and the methodological quality was evaluated as generally low. Ginkgo Biloba extract with RWM was more effective in angina relief and electrocardiogram improvement than RWM alone. Reported adverse events included epigastric discomfort, nausea, gastrointestinal reaction, and bitter taste. Ginkgo Biloba extract may have beneficial effects on patients with angina pectoris, although the low quality of existing trials makes it difficult to draw a satisfactory conclusion. More rigorous, high quality clinical trials are needed to provide conclusive evidence.

Loss estimation and damage forecast using database provided

NASA Astrophysics Data System (ADS)

Pyrchenko, V.; Byrova, V.; Petrasov, A.

2009-04-01

There is a wide spectrum of development of natural hazards is observed in Russian territory. It the necessity of investigation of numerous events of dangerous natural processes, researches of mechanisms of their development and interaction with each other (synergetic amplification or new hazards emerging) with the purpose of the forecast of possible losses. Employees of Laboratory of the analysis of geological risk IEG RAS have created a database about displays of natural hazards in territory of Russia, which contains the information on 1310 cases of their display during 1991 - 2008. The wide range of the used sources has determined certain difficulties in creation of Database and has demanded to develop a special new technique of unification of the information received at different times. One of points of this technique is classification of negative consequences of display of the natural hazards, considering a death-roll, wounded mans, victims and direct economic damage. This Database has allowed to track dynamics of natural hazards and the emergency situations caused by them (ES) for the considered period, and also to define laws of their development in territory of Russia in time and space. It gives the chance to create theoretical, methodological and methodical bases of forecasting of possible losses with a certain degree of probability for territory of Russia and for its separate regions that guarantees in the future maintenance of adequate, operative and efficient pre-emptive decision-making.

dbWFA: a web-based database for functional annotation of Triticum aestivum transcripts

PubMed Central

Vincent, Jonathan; Dai, Zhanwu; Ravel, Catherine; Choulet, Frédéric; Mouzeyar, Said; Bouzidi, M. Fouad; Agier, Marie; Martre, Pierre

2013-01-01

The functional annotation of genes based on sequence homology with genes from model species genomes is time-consuming because it is necessary to mine several unrelated databases. The aim of the present work was to develop a functional annotation database for common wheat Triticum aestivum (L.). The database, named dbWFA, is based on the reference NCBI UniGene set, an expressed gene catalogue built by expressed sequence tag clustering, and on full-length coding sequences retrieved from the TriFLDB database. Information from good-quality heterogeneous sources, including annotations for model plant species Arabidopsis thaliana (L.) Heynh. and Oryza sativa L., was gathered and linked to T. aestivum sequences through BLAST-based homology searches. Even though the complexity of the transcriptome cannot yet be fully appreciated, we developed a tool to easily and promptly obtain information from multiple functional annotation systems (Gene Ontology, MapMan bin codes, MIPS Functional Categories, PlantCyc pathway reactions and TAIR gene families). The use of dbWFA is illustrated here with several query examples. We were able to assign a putative function to 45% of the UniGenes and 81% of the full-length coding sequences from TriFLDB. Moreover, comparison of the annotation of the whole T. aestivum UniGene set along with curated annotations of the two model species assessed the accuracy of the annotation provided by dbWFA. To further illustrate the use of dbWFA, genes specifically expressed during the early cell division or late storage polymer accumulation phases of T. aestivum grain development were identified using a clustering analysis and then annotated using dbWFA. The annotation of these two sets of genes was consistent with previous analyses of T. aestivum grain transcriptomes and proteomes. Database URL: urgi.versailles.inra.fr/dbWFA/ PMID:23660284

Technology Insertion-Engineering Services Process Characterization, Task Order Number 1 (Block 1) Database Documentation Book, MANPGB

DTIC Science & Technology

1989-08-14

General Information > MANPGB is a Resource Control Center under the MANPG section of the Industrial W Products Division (MAN) at WR-ALC/ MANPGB is located...zo a N 1 I- I- LU ~a U) La ~ca LU P- 1= .: - "~0. ujN La7N LU 0 U 1I. DATE WORK CONTROL DOCUMENT . . . * ~:0IA~ r JOB ORDER NUMBER. 31J~ANTITY 4. N...30834A ---1.-- Cicleappropriate control number Clean iniao-xenlsrae. 02. Functional analysis - B- f 3 Deseal -Mt___ 04 Internal cleaning & visual. 05

Obtaining NASA Approval for use of Non-Metallic Materials in Manned Space Flight

NASA Technical Reports Server (NTRS)

Davis, Samuel E.; Wise, Harry L.

2003-01-01

Material manufacturers and suppliers are often surprised when a material commonly provided to industry is not approved for use on manned spacecraft. Often the reason is a lack of test data in environments that simulate those encountered in space applications, especially oxygen-enriched conditions, which significantly increase both the likelihood of material combustion and the propagation of a fire. This paper introduces the requirements for flight approval of non-metallic materials, focusing on material testing for human-rated space flight programs; it reviews the history of flight materials requirements and provides the rationale for such and introduces specific requirements related to testing and to good material engineering and design practices. After describing the procedure for submitting materials to be tested, the paper outlines options available if a material fails testing. In addition, this treatise introduces the National Aeronautics and Space Administration's (NASA's) Materials and Processes Technical Information System (MAPTIS), a database housing all test data produced in accordance with NASA-STD-6001, Flammability, Odor, Offgassing, and Compatibility Requirements and Test Procedures for Materials in Environments that Support Combustion.

Distribution of naturally occurring radioactivity and ¹³⁷Cs in the marine sediment of Farasan Island, southern Red Sea, Saudi Arabia.

PubMed

Al-Zahrany, A A; Farouk, M A; Al-Yousef, A A

2012-11-01

The present work is a part of a project dedicated to measure the marine radioactivity near the Saudi Arabian coasts of the Red Sea and Arabian Gulf for establishing a marine radioactivity database, which includes necessary information on the background levels of both naturally occurring and man-made radionuclides in the marine environment. Farasan Islands is a group of 84 islands (archipelago), under the administration of the Kingdom of Saudi Arabia, in the Red Sea with its main island of Farasan, which is 50 km off the coast of Jazan City. The levels of natural radioactivity of (238)U, (235)U, (226)Ra, (232)Th and (40)K and man-made radionuclides such as (137)Cs in the grab sediment and water samples around Farasan Island have been measured using gamma-ray spectroscopy. The average activity concentrations of (238)U, (235)U, (226)Ra, (232)Th, (40)K and (137)Cs in the sediment samples were found to be 35.46, 1.75, 3.31, 0.92, 34.34 and 0.14 Bq kg(-1), respectively.

Tics after traumatic brain injury.

PubMed

Ranjan, Nishant; Nair, Krishnan Padmakumari Sivaraman; Romanoski, Charles; Singh, Rajiv; Venketswara, Guruprasad

2011-01-01

Tics are involuntary non-rhythmic, stereotyped muscle contractions which can be suppressed temporarily. Tics usually start during childhood as part of Tourette syndrome. Adult onset tics are infrequent. This study reports on an adult man who developed tics 1 year after severe traumatic brain injury (TBI). Case report and review of literature. A 19-year-old man sustained TBI following a road traffic accident. He did not have tics or features of obsessive compulsive disorder before the brain injury. A year after injury he developed motor and vocal tics. Magnetic resonance image of the brain showed lesions in the basal ganglia. A search of databases Medline, EMBASE and CINHAL found only four publications on tics in adults with TBI. None of these reported cases had lesions in the basal ganglia. Tics are a rare complication of TBI. People with early onset post-traumatic tics may have had a previously unrecognized, mild tic disorder or a genetic predisposition for tics, which was unmasked by the TBI. In contrast, late post-traumatic tics could be due to delayed effects of injury on neural circuits connecting the frontal cortex and basal ganglia.

Expressing pride: Effects on perceived agency, communality, and stereotype-based gender disparities.

PubMed

Brosi, Prisca; Spörrle, Matthias; Welpe, Isabell M; Heilman, Madeline E

2016-09-01

Two experimental studies were conducted to investigate how the expression of pride shapes agency-related and communality-related judgments, and how those judgments differ when the pride expresser is a man or a woman. Results indicated that the expression of pride (as compared to the expression of happiness) had positive effects on perceptions of agency and inferences about task-oriented leadership competence, and negative effects on perceptions of communality and inferences about people-oriented leadership competence. Pride expression also elevated ascriptions of interpersonal hostility. For agency-related judgments and ascriptions of interpersonal hostility, these effects were consistently stronger when the pride expresser was a woman than a man. Moreover, the expression of pride was found to affect disparities in judgments about men and women, eliminating the stereotype-consistent differences that were evident when happiness was expressed. With a display of pride women were not seen as any more deficient in agency-related attributes and competencies, nor were they seen as any more exceptional in communality-related attributes and competencies, than were men. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Addition of oral iron to plasma transfusion in human congenital hypotransferrinemia: A 10-year observational follow-up with the effects on hematological parameters and growth.

PubMed

Aslan, Deniz

2018-02-01

Congenital hypotransferrinemia (OMIM 209300) is an extremely rare disorder of inherited iron metabolism. Since its description in 1961, only 16 cases have been reported. The defective gene and molecular defect causing this disorder and clinicolaboratory findings seen in the homozygous and heterozygous states have been documented in both humans and mice. However, due to the lack of follow-up studies of the described cases, the long-term prognosis remains unknown. We present a 10-year observational follow-up of a patient previously diagnosed on a molecular basis who was treated with a unique therapy of plasma transfusion fortified with oral iron, with satisfactory clinicolaboratory responses. © 2017 Wiley Periodicals, Inc.

Focal dermal hypoplasia (Goltz-Gorlin syndrome): a new case with a novel variant in the PORCN gene (c.1250T>C:p.F417S) and unusual spinal anomaly.

PubMed

Garavelli, Livia; Simonte, Graziella; Rosato, Simonetta; Wischmeijer, Anita; Albertini, Enrico; Guareschi, Elisa; Longo, Caterina; Albertini, Giuseppe; Gelmini, Chiara; Greco, Chiara; Errico, Stefania; Savino, Gustavo; Pavanello, Marco; Happle, Rudolf; Unger, Sheila; Superti-Furga, Andrea; Grzeschik, Karl-Heinz

2013-07-01

Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome; OMIM 305600) is a disorder that features involvement of the skin, skeletal system, and eyes. It is caused by loss-of-function mutations in the PORCN gene. We report a young girl with FDH, microphthalmos associated with colobomatous orbital cyst, dural ectasia and cystic malformation of the spinal cord, and a de novo variant in PORCN. This association has not been previously reported, and based on these observations the phenotypic spectrum of FDH might be broader than previously appreciated. It would be prudent to alter the suggested surveillance for this rare disorder. Copyright © 2013 Wiley Periodicals, Inc.

Therapy Development for the Lysosomal Storage Disease Fucosidosis using the Canine Animal Model.

PubMed

Fletcher, Jessica L; Taylor, Rosanne M

2016-06-01

Abstract Fucosidosis (OMIM 23000) is an inherited neurodegenerative lysosomal storage disease caused by a deficiency of the lysosomal hydrolase a-L-fucosidase due to mutations in the FUCA1 gene. Without enzyme-targeted therapy patients rarely survive beyond the first decade of life, and therapy options other than supportive care are limited. Hematopoietic transplants, first developed in the fucosidosis dog model, are the only treatment option available capable of delaying the disease course. However, due to the risks and exclusion criteria of this treatment additional therapies are required. The development of additional therapies including intravenous and intra-cerebrospinal fluid enzyme replacement therapy and gene therapy, which have been trialed in the canine model, will be discussed.

Clinical Heterogeneity in two patients with Noonan-like Syndrome associated with the same SHOC2 mutation.

PubMed

Capalbo, Donatella; Scala, Maria Giuseppa; Melis, Daniela; Minopoli, Giorgia; Improda, Nicola; Palamaro, Loredana; Pignata, Claudio; Salerno, Mariacarolina

2012-09-20

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM #607721) has been recently related to the invariant c.4A > G missense change in SHOC2. It is characterized by features reminiscent of Noonan syndrome. Ectodermal involvement, short stature associated to growth hormone (GH) deficiency (GHD), and cognitive deficits are common features. We compare in two patients with molecularly confirmed NS/LAH diagnosis, the clinical phenotype and pathogenetic mechanism underlying short stature. In particular, while both the patients exhibited a severe short stature, GH/IGFI axis functional evaluation revealed a different pathogenetic alteration, suggesting in one patient an upstream alteration (typical GHD) and in the other one a peripheral GH insensitivity.

Attractive non-DLVO forces induced by adsorption of monovalent organic ions.

PubMed

Smith, Alexander M; Maroni, Plinio; Borkovec, Michal

2017-12-20

Direct force measurements between negatively charged colloidal particles were carried out using an atomic force microscope (AFM) in aqueous solutions containing monovalent organic cations, namely tetraphenylarsonium (Ph 4 As + ), 1-hexyl-3-methylimidazolium (HMIM + ), and 1-octyl-3-methylimidazolium (OMIM + ). These ions adsorb to the particle surface, and induce a charge reversal. The forces become attractive at the charge neutralization point, but they are stronger than van der Waals forces. This additional and unexpected attraction decays exponentially with a decay length of a few nanometers, and is strikingly similar to the one previously observed in the presence of multivalent ions. This attractive force probably originates from coupled spontaneous charge fluctuations on the respective surfaces as initially suggested by Kirkwood and Shumaker.

Sperm RNA elements as markers of health.

PubMed

Burl, Rayanne B; Clough, Stephanie; Sendler, Edward; Estill, Molly; Krawetz, Stephen A

2018-02-01

Idiopathic infertility, an etiology not identified as part of standard clinical assessment, represents approximately 20% of all infertility cases. Current male infertility diagnosis focuses on the concentration, motility, and morphology of spermatozoa. This is of limited value when predicting birth success and of limited utility when selecting the optimum treatment. At fertilization, spermatozoa provide their genomic contribution, as well as a set of RNAs and proteins that have distinct roles in development. The potential of spermatozoal RNAs to be used as a prognostic of live birth has been shown [Jodar et al. (2015) Science Translational Medicine 7(295):295re6]. This relied on a set of 648 sperm RNA elements derived from 285 genes that are perhaps indicative of future health status. To address this tenet, the present study correlated the levels of each transcript among all samples to assess linkage between transcript absence, birth success, and possible disease association. Correlations between transcript levels of the 285 genes were analyzed amongst themselves, and within the context of the entire transcript population for these samples. The transcripts ACE, GIGYF2, and ODF2 had many negative correlations and form the majority of correlations, suggesting an important function for these transcripts. Eleven of the 285 queried genes had disease-associated variants within a sperm RNA element. Three genes, GPX4, NDRG1, and RPS24 had SREs were absent in at least one individual from the test cohort. GPX4 and RPS24 are associated with developmental defects and/or neonatal lethality. This leaves the intriguing possibility that, while sperm RNAs delivered to the oocyte inform the success of live birth, they may also be predictors of human health. GO: Gene Ontology; ART: assisted reproductive technology; IVF: in vitro fertilization; ICSI: intra-cytoplasmic sperm injection; RNA-seq: RNA-sequencing; TIC: timed intercourse; IUI: intrauterine insemination; SRE: sperm RNA elements; HPA: Human Protein Atlas; SMDS: sedaghatian-type spondylometaphyseal dysplasia; DBA: Diamond-Blackfan anemia; RPKM: reads per kilobase per million; TPM: transcripts per million; IPA: Ingenuity Pathway Analysis; OMIM: Online Mendelian Inheritance in Man.

Developing a Strategic Plan for NASA JSC's Technology Investments

NASA Technical Reports Server (NTRS)

Stecklein, Jonette M.

2012-01-01

Human space exploration has always been heavily influenced by goals to achieve a specific mission on a specific schedule. This approach drove rapid technology development, the rapidity of which adds risks as well as provides a major driver for costs. The National Aeronautics and Space Administration (NASA) is now approaching the extension of human presence throughout the solar system by balancing a proactive yet less schedule-driven development of technology with opportunistic scheduling of missions as the needed technologies are realized. This approach should provide cost effective, low risk technology development that will enable efficient and effective manned spaceflight missions. As a first step, the NASA Human Spaceflight Architecture Team (HAT) has identified a suite of critical technologies needed to support future manned missions across a range of destinations, including in cislunar space, near earth asteroid visits, lunar exploration, Mars space, and Mars exploration. The challenge now is to develop a strategy and plan for technology development that efficiently enables these missions over a reasonable time period, without increasing technology development costs unnecessarily due to schedule pressure, and subsequently mitigating development and mission risks. NASA fs Johnson Space Center (JSC), as the nation's primary center for human exploration, is addressing this challenge through an innovative approach allocating Internal Research and Development funding to projects that have been prioritized using four focus criteria, with appropriate importance weighting. These four focus criteria are the Human Space Flight Technology Needs, JSC Core Technology Competencies, Commercialization Potential, and Partnership Potential. The inherent coupling in these focus criteria have been captured in a database and have provided an initial prioritization for allocation of technology development research funding. This paper will describe this process and this database, and the preliminary technology development prioritization results.

Herbal medicine (Hyeolbuchukeo-tang or Xuefu Zhuyu decoction) for treating primary dysmenorrhoea: protocol for a systematic review of randomised controlled trials.

PubMed

Jo, Junyoung; Leem, Jungtae; Lee, Jin Moo; Park, Kyoung Sun

2017-06-15

Primary dysmenorrhoea is menstrual pain without pelvic pathology and is the most common gynaecological condition in women. Xuefu Zhuyudecoction (XZD) or Hyeolbuchukeo-tang, a traditional herbal formula, has been used as a treatment for primary dysmenorrhoea. The purpose of this study is to assess the current published evidence regarding XZD as treatment for primary dysmenorrhoea. The following databases will be searched from their inception until April 2017: MEDLINE (via PubMed), Allied and Complementary Medicine Database (AMED), EMBASE, The Cochrane Library, six Korean medical databases (Korean Studies Information Service System, DBPia, Oriental Medicine Advanced Searching Integrated System, Research Information Service System, Korea Med and the Korean Traditional Knowledge Portal), three Chinese medical databases (China National Knowledge Infrastructure (CNKI), Wan Fang Database and Chinese Scientific Journals Database (VIP)) and one Japanese medical database (CiNii). Randomised clinical trials (RCTs) that will be included in this systematic review comprise those that used XZD or modified XZD. The control groups in the RCTs include no treatment, placebo, conventional medication or other treatments. Trials testing XZD as an adjunct to other treatments and studies where the control group received the same treatment as the intervention group will be also included. Data extraction and risk of bias assessments will be performed by two independent reviewers. The risk of bias will be assessed with the Cochrane risk of bias tool. All statistical analyses will be conducted using Review Manager software (RevMan V.5.3.0). This systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print. The review will benefit patients and practitioners in the fields of traditional and conventional medicine. CRD42016050447. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Risk formulation for the sonic effects of offshore wind farms on fish in the EU region.

PubMed

Kikuchi, Ryunosuke

2010-02-01

In 2007, European leaders agreed to source 20% of their energy needs from renewable energy; since that time, offshore wind farms have been receiving attention in the European Union (EU). In 2008, the European Community submitted a proposal to the United Nations Environment Program (UNEP) in order to combat marine noise pollution. In consideration of these facts, the present paper aims to deduce a preliminary hypothesis and its formulation for the effect of offshore wind farm noise on fish. The following general picture is drawn: the short-term potential impact during pre-construction; the short-term intensive impact during construction; and the physiological and/or masking effects that may occur over a long period while the wind farm is in operation. The EU's proposal to UNEP includes noise databases that list the origins of man-made sounds; it is advisable that offshore wind farms should be listed in the noise databases in order to promote rational environment management. Copyright 2009 Elsevier Ltd. All rights reserved.

Mutational Insights into the Roles of Amino Acid Residues in Ligand Binding for Two Closely Related Family 16 Carbohydrate Binding Modules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Xiaoyun; Agarwal, Vinayak; Dodd, Dylan

2010-11-22

Carbohydrate binding modules (CBMs) are specialized proteins that bind to polysaccharides and oligosaccharides. Caldanaerobius polysaccharolyticus Man5ACBM16-1/CBM16-2 bind to glucose-, mannose-, and glucose/mannose-configured substrates. The crystal structures of the two proteins represent the only examples in CBM family 16, and studies that evaluate the roles of amino acid residues in ligand binding in this family are lacking. In this study, we probed the roles of amino acids (selected based on CBM16-1/ligand co-crystal structures) on substrate binding. Two tryptophan (Trp-20 and Trp-125) and two glutamine (Gln-81 and Gln-93) residues are shown to be critical in ligand binding. Additionally, several polar residues thatmore » flank the critical residues also contribute to ligand binding. The CBM16-1 Q121E mutation increased affinity for all substrates tested, whereas the Q21G and N97R mutants exhibited decreased substrate affinity. We solved CBM/substrate co-crystal structures to elucidate the molecular basis of the increased substrate binding by CBM16-1 Q121E. The Gln-121, Gln-21, and Asn-97 residues can be manipulated to fine-tune ligand binding by the Man5A CBMs. Surprisingly, none of the eight residues investigated was absolutely conserved in CBM family 16. Thus, the critical residues in the Man5A CBMs are either not essential for substrate binding in the other members of this family or the two CBMs are evolutionarily distinct from the members available in the current protein database. Man5A is dependent on its CBMs for robust activity, and insights from this study should serve to enhance our understanding of the interdependence of its catalytic and substrate binding modules.« less

Differential GPS/inertial navigation approach/landing flight test results

NASA Technical Reports Server (NTRS)

Snyder, Scott; Schipper, Brian; Vallot, Larry; Parker, Nigel; Spitzer, Cary

1992-01-01

Results of a joint Honeywell/NASA-Langley differential GPS/inertial flight test conducted in November 1990 are discussed focusing on postflight data analysis. The test was aimed at acquiring a system performance database and demonstrating automatic landing based on an integrated differential GPS/INS with barometric and radar altimeters. Particular attention is given to characteristics of DGPS/inertial error and the magnitude of the differential corrections and vertical channel performance with and without altimeter augmentation. It is shown that DGPS/inertial integrated with a radar altimeter is capable of providing a precision approach and autoland guidance of manned return space vehicles within the Space Shuttle accuracy requirements.

DataHub: Knowledge-based data management for data discovery

NASA Astrophysics Data System (ADS)

Handley, Thomas H.; Li, Y. Philip

1993-08-01

Currently available database technology is largely designed for business data-processing applications, and seems inadequate for scientific applications. The research described in this paper, the DataHub, will address the issues associated with this shortfall in technology utilization and development. The DataHub development is addressing the key issues in scientific data management of scientific database models and resource sharing in a geographically distributed, multi-disciplinary, science research environment. Thus, the DataHub will be a server between the data suppliers and data consumers to facilitate data exchanges, to assist science data analysis, and to provide as systematic approach for science data management. More specifically, the DataHub's objectives are to provide support for (1) exploratory data analysis (i.e., data driven analysis); (2) data transformations; (3) data semantics capture and usage; analysis-related knowledge capture and usage; and (5) data discovery, ingestion, and extraction. Applying technologies that vary from deductive databases, semantic data models, data discovery, knowledge representation and inferencing, exploratory data analysis techniques and modern man-machine interfaces, DataHub will provide a prototype, integrated environement to support research scientists' needs in multiple disciplines (i.e. oceanography, geology, and atmospheric) while addressing the more general science data management issues. Additionally, the DataHub will provide data management services to exploratory data analysis applications such as LinkWinds and NCSA's XIMAGE.

Novel and recurrent FERMT1 gene mutations in Kindler syndrome.

PubMed

Techanukul, Tanasit; Sethuraman, Gomathy; Zlotogorski, Abraham; Horev, Liran; Macarov, Michal; Trainer, Alison; Fong, Kenneth; Lens, Marko; Medenica, Ljiljana; Ramesh, Venkatesh; McGrath, John A; Lai-Cheong, Joey E

2011-05-01

Kindler syndrome (OMIM 173650) is an autosomal recessive condition characterized by skin blistering, skin atrophy, photosensitivity, colonic inflammation and mucosal stenosis. Fewer than 100 cases have been described in the literature. First reported in 1954, the molecular basis of Kindler syndrome was elucidated in 2003 with the discovery of FERMT1 (KIND1) loss-of-function mutations in affected individuals. The FERMT1 gene encodes kindlin-1 (also known as fermitin family homologue 1), a 77 kDa protein that localizes at focal adhesions, where it plays an important role in integrin signalling. In the current study, we describe five novel and three recurrent loss-of-function FERMT1 mutations in eight individuals with Kindler syndrome, and provide an overview of genotype-phenotype correlation in this disorder.

Aversive and non-aversive memory impairment in the mucopolysaccharidosis II mouse model.

PubMed

Azambuja, Amanda Stapenhorst; Correa, Lilian; Gabiatti, Bernardo Pappi; Martins, Giselle Renata; de Oliveira Franco, Álvaro; Ribeiro, Maria Flávia Marques; Baldo, Guilherme

2018-02-01

Hunter syndrome (MPS II, OMIM 309900) is a lysosomal storage disorder due to deficient iduronate sulphatase activity. Patients present multiple cognitive alterations, and the aim of this work was to verify if MPS II mice also present some progressive cognitive alterations. For that, MPS II mice from 2 to 6 months of age were submitted to repeated open field and inhibitory avoidance tests to evaluate memory parameters. MPS II mice presented impaired memory at 6 months evaluated by open field test. They also performed poorly in the inhibitory avoidance test from 4 months. We conclude that MPS II mice develop cognitive alterations as the disease progresses. These tests can be used in the future to study the efficacy of therapeutic approaches in the central nervous system.

Genoa Syndrome and Central Diabetes Insipidus: A Case Report

PubMed Central

Şıklar, Zeynep; Erdeve, Şenay Savaş; Berberoğlu, Merih; Deda, Gülhiz; Tıraş, Serap Teber; Fitöz, Suat; Öçal, Gönül

2010-01-01

Genoa syndrome was first described by Camera et al in 1993 in two patients with semilobar holoprosencephaly (HPE), craniosynostosis and abnormal small hands with cone−shaped epiphyses and hypoplastic terminal phalanges of fingers (OMIM: 601370). In 2001, Lapunzina et al reported a case of craniosynostosis and HPE associated with several other malformations and suggested that these findings could be attributed to a severe form of Genoa syndrome or to a newly recognized syndrome. Endocrinopathies in association with HPE are frequently reported in the literature. Diabetes insipidus, hypothyroidism, hypocortisolism, and growth hormone deficiency are frequently associated with HPE. We here report a case of semilobar HPE, craniosynostosis and cleft lip/palate, possibly a case of Genoa syndrome, associated with central diabetes insipidus. Conflict of interest:None declared. PMID:21274346

The genetics of cholesteatoma. A systematic review using narrative synthesis.

PubMed

Jennings, B A; Prinsley, P; Philpott, C; Willis, G; Bhutta, M F

2018-02-01

A cholesteatoma is a mass of keratinising epithelium in the middle ear. It is a rare disorder that is associated with significant morbidity, and its causative risk factors are poorly understood; on a global scale, up to a million people are affected by this each year. We have conducted a systematic literature review to identify reports about the heritability of cholesteatoma or any constitutional genetic factors that may be associated with its aetiology. A systematic search of MEDLINE (EBSCO) and two databases of curated genetic research (OMIM and Phenopedia) was conducted. The participants and populations of interest for this review were people treated for cholesteatoma and their family members. The studies of interest reported evidence of heritability for the trait, or any association with congenital syndromes and particular genetic variants. The searches identified 449 unique studies, of which 35 were included in the final narrative synthesis. A narrative synthesis was conducted, and data were tabulated to record characteristics, including study design, genetic data and author conclusions. Most of the studies identified in the literature search, and described here, are case reports and so represent the lowest level of evidence. In a few case reports, congenital and acquired cholesteatomas have been shown to segregate within families in the pattern typical of a monogenic or oligogenic disorder with incomplete penetrance. Evidence from syndromic cases could suggest that genes controlling ear morphology may be risk factors for cholesteatoma formation. This is the first systematic review about the genetics of cholesteatoma, and we have identified a small body of relevant literature that provides evidence of a heritable component for its aetiology. Cholesteatoma is a complex and heterogeneous clinical phenotype, and it is often associated with chronic otitis media and with some rare congenital syndromes known to affect ear morphology and related pathologies. © 2017 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd.

Application of array-comparative genomic hybridization in tetralogy of Fallot

PubMed Central

Liu, Lin; Wang, Hong-Dan; Cui, Cun-Ying; Wu, Dong; Li, Tao; Fan, Tai-Bing; Peng, Bang-Tian; Zhang, Lian-Zhong; Wang, Cheng-Zeng

2016-01-01

Abstract To explore the underlying pathogenesis and provide references for genetic counseling and prenatal gene diagnosis, we analyzed the chromosome karyotypes and genome-wide copy number variations (CNVs) in 86 patients with tetralogy of Fallot (TOF) by G-banding karyotype analysis and array-comparative genomic hybridization (aCGH), respectively. And then quantitative polymerase chain reaction was used to validate these candidate CNVs. Based on their different properties, CNVs were categorized into benign CNVs, suspiciously pathogenic CNVs, and indefinite CNVs. Data analysis was based on public databases such as UCSC, DECIPHER, DGV, ISCA, and OMIM. The karyotype was normal in all the 86 patients with TOF. CNVs were detected in 11 patients by aCGH and quantitative polymerase chain reaction. Patient no. 0001, 0010, and 0029 had 2.52-Mb deletion in the chromosome 22q11.21 region; patient no. 0008 had both 595- and 428-kb duplications, respectively, in 12p12.3p12.2 and 14q23.2q23.3 regions; patient no. 0009 had 1.46-Mb duplication in the 1q21.1q21.2 region; patient no. 0016 had 513-kb duplication in the 1q42.13 region; patient no. 0024 had 292-kb duplication in the 16q11.2 region; patient no. 0026 had 270-kb duplication in the 16q24.1 region; patient no. 0028 had 222-kb deletion in the 7q31.1 region; patient no. 0033 had 1.73-Mb duplication in the 17q12 region; and patient no. 0061 had 5.79-Mb deletion in the 1p36.33p36.31 region. aCGH can accurately detect CNVs in the patients with TOF. This is conducive to genetic counseling and prenatal diagnosis for TOF and provides a new clue and theoretical basis for exploring the pathogenesis of congenital heart disease. PMID:27930557

Application of array-comparative genomic hybridization in tetralogy of Fallot.

PubMed

Liu, Lin; Wang, Hong-Dan; Cui, Cun-Ying; Wu, Dong; Li, Tao; Fan, Tai-Bing; Peng, Bang-Tian; Zhang, Lian-Zhong; Wang, Cheng-Zeng

2016-12-01

To explore the underlying pathogenesis and provide references for genetic counseling and prenatal gene diagnosis, we analyzed the chromosome karyotypes and genome-wide copy number variations (CNVs) in 86 patients with tetralogy of Fallot (TOF) by G-banding karyotype analysis and array-comparative genomic hybridization (aCGH), respectively. And then quantitative polymerase chain reaction was used to validate these candidate CNVs. Based on their different properties, CNVs were categorized into benign CNVs, suspiciously pathogenic CNVs, and indefinite CNVs. Data analysis was based on public databases such as UCSC, DECIPHER, DGV, ISCA, and OMIM.The karyotype was normal in all the 86 patients with TOF. CNVs were detected in 11 patients by aCGH and quantitative polymerase chain reaction. Patient no. 0001, 0010, and 0029 had 2.52-Mb deletion in the chromosome 22q11.21 region; patient no. 0008 had both 595- and 428-kb duplications, respectively, in 12p12.3p12.2 and 14q23.2q23.3 regions; patient no. 0009 had 1.46-Mb duplication in the 1q21.1q21.2 region; patient no. 0016 had 513-kb duplication in the 1q42.13 region; patient no. 0024 had 292-kb duplication in the 16q11.2 region; patient no. 0026 had 270-kb duplication in the 16q24.1 region; patient no. 0028 had 222-kb deletion in the 7q31.1 region; patient no. 0033 had 1.73-Mb duplication in the 17q12 region; and patient no. 0061 had 5.79-Mb deletion in the 1p36.33p36.31 region.aCGH can accurately detect CNVs in the patients with TOF. This is conducive to genetic counseling and prenatal diagnosis for TOF and provides a new clue and theoretical basis for exploring the pathogenesis of congenital heart disease.

Genotype–phenotype study of familial haemophagocytic lymphohistiocytosis type 3

PubMed Central

Sieni, Elena; Cetica, Valentina; Santoro, Alessandra; Beutel, Karin; Mastrodicasa, Elena; Meeths, Marie; Ciambotti, Benedetta; Brugnolo, Francesca; zur Stadt, Udo; Pende, Daniela; Moretta, Lorenzo; Griffiths, Gillian M; Henter, Jan-Inge; Janka, Gritta; Aricò, Maurizio

2014-01-01

Background Mutations of UNC13D are causative for familial haemophagocytic lymphohistiocytosis type 3 (FHL3; OMIM 608898). Objective To carry out a genotype–phenotype study of patients with FHL3. Methods A consortium of three countries pooled data on presenting features and mutations from individual patients with biallelic UNC13D mutations in a common database. Results 84 patients with FHL3 (median age 4.1 months) were reported from Florence, Italy (n=54), Hamburg, Germany (n=18), Stockholm, Sweden (n=12). Their ethnic origin was Caucasian (n=57), Turkish (n=10), Asian (n=7), Hispanic (n=4), African (n=3) (not reported (n=3)). Thrombocytopenia was present in 94%, splenomegaly in 96%, fever in 89%. The central nervous system (CNS) was involved in 49/81 (60%) patients versus 36% in patients with FHL2 (p=0.001). A combination of fever, splenomegaly, thrombocytopenia and hyperferritinaemia was present in 71%. CD107a expression, NK activity and Munc 13-4 protein expression were absent or reduced in all but one of the evaluated patients. 54 different mutations were observed, including 15 new ones: 19 missense, 14 deletions or insertions, 12 nonsense, nine splice errors. None was specific for ethnic groups. Patients with two disruptive mutations were younger than patients with two missense mutations (p<0.001), but older than comparable patients with FHL2 (p=0.001). Conclusion UNC13D mutations are scattered over the gene. Ethnic-specific mutations were not identified. CNS involvement is more common than in FHL2; in patients with FHL3 and disruptive mutations, age at diagnosis is significantly higher than in FHL2. The combination of fever, splenomegaly, thrombocytopenia and hyperferritinaemia appears to be the most easily and frequently recognised clinical pattern and their association with defective granule release assay may herald FHL3. PMID:21248318

Moyamoya syndrome as a risk factor for stroke in Saudi children. Novel and usual associations.

PubMed

Salih, Mustafa A; Murshid, Waleed R; Al-Salman, Mussaad M; Abdel-Gader, Abdel-Galil M; Al-Jarallah, Ahmed A; Alorainy, Ibrahim A; Hassan, Hamdy H; Kentab, Amal Y; Van Maldergem, Lionel; Othman, Saleh A; El-Desouki, Mahmoud I; Elgamal, Essam A

2006-03-01

To report on moyamoya syndrome (MMS) as a risk factor for stroke in a prospective and retrospective cohort of Saudi children. The usual and novel associations of MMS in this cohort will also be described. Children with stroke were evaluated at the Division of Pediatric Neurology at King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia during the periods July 1992 to February 2001 (retrospective study) and February 2001 to March 2003 (prospective study). Investigations for suspected cases included hemostatic assays, biochemical, and serological tests. Neuroimaging included CT, MRI, magnetic resonance angiography (MRA), single photon computerized tomography (SPECT) brain scan and conventional cerebral angiography. Moyamoya syndrome was the underlying risk factor for stroke in 6 (5.8%) of the 104 children (aged one month to 12 years). They were 4 females and 2 males. Their first cerebral ischemic event occurred at a mean age of 45 months (median = 44 months, range 17-66 months). In all 6 cases, MMS was associated with an underlying hematologic abnormality or other diseases. Protein C deficiency was identified in one girl and protein S deficiency in another. Two patients had respectively, sickle cell disease (SCD) and sickle cell-beta-thalassemia (S beta-thalassemia), which had been associated in the latter with membranous ventricular septal defect. Adams-Oliver syndrome (AOS, OMIM 100300) was associated with MMS in an 18-month-old girl. A 4-year-old boy had wrinkly skin syndrome (WSS, OMIM 278250) phenotype. The association of MMS and protein C deficiency was first reported in this cohort of patients, whereas the association of the syndrome with WWS and AOS has not, hitherto, been described. The 3 patients who had MMS associated with protein C deficiency, SCD, and AOS underwent successful revascularization surgery in the form of encephaloduroarteriosynangiosis. Moyamoya syndrome constitutes an important risk factor of stroke in Saudi children. Comprehensive clinical evaluation and investigations, including screening for thrombophilia and neuroimaging studies, are required for the primary diagnosis of the disease and for unraveling other diseases associated with MMS. This will help in managing these patients and in guiding genetic counseling for their families.

Geolocation of man-made reservoirs across terrains of varying complexity using GIS

NASA Astrophysics Data System (ADS)

Mixon, David M.; Kinner, David A.; Stallard, Robert F.; Syvitski, James P. M.

2008-10-01

The Reservoir Sedimentation Survey Information System (RESIS) is one of the world's most comprehensive databases of reservoir sedimentation rates, comprising nearly 6000 surveys for 1819 reservoirs across the continental United States. Sediment surveys in the database date from 1904 to 1999, though more than 95% of surveys were entered prior to 1980, making RESIS largely a historical database. The use of this database for large-scale studies has been limited by the lack of precise coordinates for the reservoirs. Many of the reservoirs are relatively small structures and do not appear on current USGS topographic maps. Others have been renamed or have only approximate (i.e. township and range) coordinates. This paper presents a method scripted in ESRI's ARC Macro Language (AML) to locate the reservoirs on digital elevation models using information available in RESIS. The script also delineates the contributing watersheds and compiles several hydrologically important parameters for each reservoir. Evaluation of the method indicates that, for watersheds larger than 5 km 2, the correct outlet is identified over 80% of the time. The importance of identifying the watershed outlet correctly depends on the application. Our intent is to collect spatial data for watersheds across the continental United States and describe the land use, soils, and topography for each reservoir's watershed. Because of local landscape similarity in these properties, we show that choosing the incorrect watershed does not necessarily mean that the watershed characteristics will be misrepresented. We present a measure termed terrain complexity and examine its relationship to geolocation success rate and its influence on the similarity of nearby watersheds.

[A computer-aided image diagnosis and study system].

PubMed

Li, Zhangyong; Xie, Zhengxiang

2004-08-01

The revolution in information processing, particularly the digitizing of medicine, has changed the medical study, work and management. This paper reports a method to design a system for computer-aided image diagnosis and study. Combined with some good idea of graph-text system and picture archives communicate system (PACS), the system was realized and used for "prescription through computer", "managing images" and "reading images under computer and helping the diagnosis". Also typical examples were constructed in a database and used to teach the beginners. The system was developed by the visual developing tools based on object oriented programming (OOP) and was carried into operation on the Windows 9X platform. The system possesses friendly man-machine interface.

[Development of fixed-base full task space flight training simulator].

PubMed

Xue, Liang; Chen, Shan-quang; Chang, Tian-chun; Yang, Hong; Chao, Jian-gang; Li, Zhi-peng

2003-01-01

Fixed-base full task flight training simulator is a very critical and important integrated training facility. It is mostly used in training of integrated skills and tasks, such as running the flight program of manned space flight, dealing with faults, operating and controlling spacecraft flight, communicating information between spacecraft and ground. This simulator was made up of several subentries including spacecraft simulation, simulating cabin, sight image, acoustics, main controlling computer, instructor and assistant support. It has implemented many simulation functions, such as spacecraft environment, spacecraft movement, communicating information between spacecraft and ground, typical faults, manual control and operating training, training control, training monitor, training database management, training data recording, system detecting and so on.

"Gender aware therapy" for professional men in a day treatment center.

PubMed

Robertson, John M; Williams, Betsy White

2010-09-01

High accountability men in the medical, legal, corporate, and mental health professions sometimes engage in behavior that violates their fiduciary responsibilities. These highly skilled men may engage in disruptive or explosive behavior, cross sexual boundaries with clients or patients, abuse substances, or have other psychiatric problems that compromise their workplace performance. When this occurs, licensing boards, professional societies, or supervising executives often require the dysregulated man to seek assistance. This article reports on ways the Professional Renewal Center incorporates recommendations from "Gender Aware Therapy" in developing a male-friendly approach to conducting comprehensive multidisciplinary psychological assessments, and to providing intensive, multimodal, weeks-long treatment services. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

JAMSTEC multibeam surveys and submersible dives around the Hawaiian Islands: a collaborative Japan-USA exploration of Hawaii's deep seafloor

USGS Publications Warehouse

Robinson, Joel E.; Eakins, Barry W.; Kanamatsu, Toshiya; Naka, Jiro; Takahashi, Eiichi; Satake, Kenji; Smith, John R.; Clague, David A.; Yokose, Hisayoshi

2006-01-01

This database release, USGS Data Series 171, contains data collected during four Japan-USA collaborative cruises that characterize the seafloor around the Hawaiian Islands. The Japan Agency for Marine-Earth Science and Technology (JAMSTEC) sponsored cruises in 1998, 1999, 2001, and 2002, to build a greater understanding of the deep marine geology around the Hawaiian Islands. During these cruises, scientists surveyed over 600,000 square kilometers of the seafloor with a hull-mounted multibeam seafloor-mapping sonar system (SEA BEAM® 2112), observed the seafloor and collected samples using robotic and manned submersible dives, collected dredge and piston-core samples, and performed single-channel seismic surveys.

A Situation Awareness Assistant for Human Deep Space Exploration

NASA Technical Reports Server (NTRS)

Boy, Guy A.; Platt, Donald

2013-01-01

This paper presents the development and testing of a Virtual Camera (VC) system to improve astronaut and mission operations situation awareness while exploring other planetary bodies. In this embodiment, the VC is implemented using a tablet-based computer system to navigate through inter active database application. It is claimed that the advanced interaction media capability of the VC can improve situation awareness as the distribution of hu man space exploration roles change in deep space exploration. The VC is being developed and tested for usability and capability to improve situation awareness. Work completed thus far as well as what is needed to complete the project will be described. Planned testing will also be described.

Are we doing any good by doing really well? (Where's the Bacon?).

PubMed

Herbert, Donald

2003-04-01

Francis Bacon, who with Rene Decartes laid the intellectual foundations for Western science in the seventeenth century, asserted that the purpose of all knowledge is "action in the production of works for ... the relief of man's estate." We assess briefly several aspects of a few of the current efforts directed to the production of such "works" with respect to such "relief" as they may provide: cancer mortality, the medical literature, evidence-based medicine, clinical trials, observational databases and criteria for the promotion and tenure of the medical faculty. We suggest why each of these efforts appears to have failed to some degree and then propose some measures that may possibly serve as correctives.

Effect of square stepping exercise for older adults to prevent fall and injury related to fall: systematic review and meta-analysis of current evidences.

PubMed

Fisseha, Berihu; Janakiraman, Balamurugan; Yitayeh, Asmare; Ravichandran, Hariharasudhan

2017-02-01

Falls and fall related injuries become an emerging health problem among older adults. As a result a review of the recent evidences is needed to design a prevention strategy. The aim of this review was to determine the effect of square stepping exercise (SSE) for fall down injury among older adults compared with walking training or other exercises. An electronic database search for relevant randomized control trials published in English from 2005 to 2016 was conducted. Articles with outcome measures of functional reach, perceived health status, fear of fall were included. Quality of the included articles was rated using Physiotherapy Evidence Database (PEDro) scale and the pooled effect of SSE was obtained by Review Manager (RevMan5) software. Significant effect of SSE was detected over walking or no treatment to improve balance as well to prevent fear of fall and improve perceived health status. The results of this systematic review proposed that SSE significantly better than walking or no treatment to prevent fall, prevent fear of fall and improve perceived health status.

Homicides by older offenders in New South Wales between 1993 and 2010.

PubMed

Reutens, Sharon; Nielssen, Olav; Large, Matthew

2015-10-01

Homicides by older people are rare and might differ from those committed by younger people. To investigate the characteristics of older homicide offenders in New South Wales (NSW), Australia. A systematic search of legal, criminological and media databases for cases of homicide committed by people in NSW aged 55 and over, during the 18 years from 1993 to 2010. Eighty-seven cases were identified through databases. Legal documents were obtained for 70 offenders, comprising about 5% of homicides committed in NSW in the period of the study. The proportions of male offenders and rates of firearm use were similar to other age groups. Twelve of the 14 homicides using guns occurred outside the metropolitan area. Older offenders were more likely to have cognitive impairment or psychotic illness. Victims were more likely to be female and in a domestic relationship with the offender. Homicide by an older person is rare, and more commonly involves a man killing a family member. Correctional facilities will increasingly have to consider the needs of older people serving long sentences. © The Royal Australian and New Zealand College of Psychiatrists 2015.

[The research progress of Treacher Collins syndrome].

PubMed

Wang, Pu; Fan, Xinmiao; Fan, Yue

2016-02-01

Treacher Collins syndrome (TCS, OMIM 154500), also known as Franceschetti-Klein syndrome, is a rare disorder that affects the first and second branchial arches. The estimated incidence is 1/50 000 live births. Mutations in TCOF1 (78%-93%) and POLR1C or POLR1D (8%) cause the disease. Most of TCS cases are inherited in a dominant pattern, while a small proportion are inherited in a recessive pattern. TCS has a variable phenotype with typical clinical characteristics including downward-slant of palpebral fissure, malar hypoplasia, mandibular hypoplasia and microtia. TCS management is a multidisciplinary affair, as interventions range from reconstructive to psychosocial. For hearing rehabilitation, TCS patients may have the choices of BAHA, ponto, vibrant soundbridge or bonebridge implantation. In this review, we summarize the TCS clinical malformations, diagnosis, genetics, management and auditory rehabilitation.

Hereditary motor and sensory neuropathy with agenesis of the corpus callosum.

PubMed

Dupré, Nicolas; Howard, Heidi C; Mathieu, Jean; Karpati, George; Vanasse, Michel; Bouchard, Jean-Pierre; Carpenter, Stirling; Rouleau, Guy A

2003-07-01

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (OMIM 218000) is an autosomal recessive disease of early onset characterized by a delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, a variable degree of agenesis of the corpus callosum, amyotrophy, hypotonia, and cognitive impairment. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) predominantly because of a founder effect. The gene defect responsible for this disorder recently has been identified, and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. Herein, we provide the first extensive review of this disorder, covering epidemiological, clinical, and molecular genetic studies.

A homozygous mutation in the stem II domain of RNU4ATAC causes typical Roifman syndrome.

PubMed

Dinur Schejter, Yael; Ovadia, Adi; Alexandrova, Roumiana; Thiruvahindrapuram, Bhooma; Pereira, Sergio L; Manson, David E; Vincent, Ajoy; Merico, Daniele; Roifman, Chaim M

2017-01-01

Roifman syndrome (OMIM# 616651) is a complex syndrome encompassing skeletal dysplasia, immunodeficiency, retinal dystrophy and developmental delay, and is caused by compound heterozygous mutations involving the Stem II region and one of the other domains of the RNU4ATAC gene. This small nuclear RNA gene is essential for minor intron splicing. The Canadian Centre for Primary Immunodeficiency Registry and Repository were used to derive patient information as well as tissues. Utilising RNA sequencing methodologies, we analysed samples from patients with Roifman syndrome and assessed intron retention. We demonstrate that a homozygous mutation in Stem II is sufficient to cause the full spectrum of features associated with typical Roifman syndrome. Further, we demonstrate the same pattern of aberration in minor intron retention as found in cases with compound heterozygous mutations.

Poikiloderma with neutropenia, Clericuzio type, in a family from Morocco.

PubMed

Mostefai, Rahima; Morice-Picard, Fanny; Boralevi, Franck; Sautarel, Michel; Lacombe, Didier; Stasia, Marie José; McGrath, John; Taïeb, Alain

2008-11-01

Three siblings from Morocco consanguineous family presented with cutaneous poikiloderma following postnatal ichthyosiform lesions, associated with papillomatous lesions, palmoplantar keratoderma, pachyonychia of toenails, fragile carious teeth, and lachrymal duct obstruction. Photosensitivity and blistering improved with age. Atrophic scars were prominent on the limbs. Neutropenia developed in the first year secondary to dysmyelopoiesis affecting the granulocyte lineage, associated with a polyclonal hypergammaglobulinemia. Several broncho-pulmonary infectious episodes complicated the evolution, and cystic fibrosis was first considered on the basis of repeated abnormal sweat chloride tests but not confirmed by molecular analyses. This autosomal recessive disorder matches that described originally as poikiloderma with neutropenia-Clericuzio type in Navajo Indians (OMIM 604173). It is discussed within the group of the major hereditary poikiloderma disorders, that is, Rothmund-Thomson syndrome, dyskeratosis congenita, and Kindler syndrome. Copyright 2008 Wiley-Liss, Inc.

The effectiveness of evidence-based nursing on development of nursing students' critical thinking: A meta-analysis.

PubMed

Cui, Chuyun; Li, Yufeng; Geng, Dongrong; Zhang, Hui; Jin, Changde

2018-06-01

The aim of this meta-analysis was to assess the effectiveness of evidence-based nursing (EBN) on the development of critical thinking for nursing students. A systematic literature review of original studies on randomized controlled trials was conducted. The relevant randomized controlled trials were retrieved from multiple electronic databases including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health (CINAHL), Chinese BioMed Database (CBM), China National Knowledge Infrastructure (CNKI), and WanFang Database. In order to make a systematic evaluation, studies were selected according to inclusion and exclusion criteria, and then according to extracted data and assessed quality. The data extraction was completed by two independent reviewers, and the methodological quality assessment was completed by another two reviewers. All of the data was analyzed by the software RevMan5.3. A total of nine studies with 1079 nursing students were chosen in this systematic literature review. The result of this meta-analysis showed that the effectiveness of evidence-based nursing was superior to that of traditional teaching on nursing students' critical thinking. The results of this meta-analysis indicate that evidence-based nursing could help nursing students to promote their development of critical thinking. More researches with higher quality and larger sample size can be analyzed in the further. Copyright © 2018. Published by Elsevier Ltd.

The Clinical Efficacy of Yindanxinnaotong Soft Capsule in the Treatment of Stroke and Angina Pectoris: A Meta-Analysis

PubMed Central

Liu, Yue

2017-01-01

Objective. To systematically evaluate the clinical efficacy of Yindanxinnaotong (YD) soft capsule in adult patients with cardiovascular diseases (stroke and angina pectoris). Methods. We electronically searched databases including Medline, PubMed, Chinese National Knowledge Infrastructure (CNKI), Cqvip Database (VIP), and Wanfang Database for published articles of randomized controlled trials (RCTs) of YD capsule in treating stroke and angina pectoris. The meta-analysis was performed using RevMan 5.3 software. Results. 49 RCTs involving 6195 subjects with cardiovascular diseases (angina pectoris and stroke) were included. Compared with western conventional medicine (WCM) and/or other Chinese medicines, YD plus WCM therapeutic regimen could significantly improve the efficacy rate (RR = 1.21, 95% CI (1.17, 1.25), P < 0.00001 for angina pectoris, RR = 1.24, 95% CI (1.18, 1.31), P < 0.00001 for stroke), showing the clinical value. In addition, the therapeutic efficiency of WCM plus YD capsule regimen is better than that of WCM alone in improving CRP (MD = −2.07, 95% CI (−3.97, −0.17), P = 0.03 <0.05) and TG (MD = −0.37, 95% CI (−0.52, −0.23), P < 0.0001). Conclusion. YD is effective in the treatment of cardiovascular diseases (angina pectoris and stroke) in adults, and WCM plus YD therapeutic regimen can significantly improve the effective rate in the clinic. PMID:28539962

Earthquakes in the context of the natural and man-made events. An epidemiologic reflexion

NASA Astrophysics Data System (ADS)

Oliveira, C. S.

2003-04-01

In the last few years a great interest has been growing for studying, in a detailed way, the impact of natural and man-made disasters, by quantifying their consequences on the human community. Such interest could only be possible due to the easier way the information circulates nowadays and how it can be made available to interested persons. We consulted a few elements of published information from a wide variety of sources and compared with elements gathered by ourselves. Many consulted results are taken from the insurance industry, especially from recent years; others from books or through the internet. A brief discussion on the kind of quality that the information should exhibit is made for a few cases. Earthquakes are analysed in the context of natural and man-made disasters, and statistics are shown for the 20th century, with greater emphasis in its second half. Data refers mainly the number of events, classifying them, number of deaths, injuries and homeless, and economic direct impact. In many instances the values by different sources present large uncertainties, especially in what concerns the economic impact. Time evolution is viewed considering the growing of population, housing and industry and the implementation of seismic codes. More precise data from recent years are used to confront the numbers referring larger periods of time. Comparisons are established among the various types of events at the world and regional levels, in order to define an index for the perception of risks. A recommendation for the setting common databases at the international level with this data is strongly made in order to reduce uncertainties and cover more wide fields of information

New crystal forms of Diocleinae lectins in the presence of different dimannosides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreno, Frederico Bruno Mendes Batista; Bezerra, Gustavo Arruda; Oliveira, Taianá Maia de

2006-11-01

The crystallization and preliminary X-ray data of Canavalia gladiata lectin (CGL) and C. maritima lectin (CML) complexed with Man(α1-2)Man(α1)OMe, Man(α1-3)Man(α1)OMe and Man(α1-4)Man(α1)OMe in two crystal forms [the complexes with Man(α1-3)Man(α1)OMe and Man(α1-4)Man(α1)OMe crystallized in space group P3{sub 2} and those with Man(α1-2)Man(α1)OMe crystallized in space group I222], which differed from those of the native proteins (P2{sub 1}2{sub 1}2 for CML and C222 for CGL), are reported. Studying the interactions between lectins and sugars is important in order to explain the differences observed in the biological activities presented by the highly similar proteins of the Diocleinae subtribe. Here, the crystallization andmore » preliminary X-ray data of Canavalia gladiata lectin (CGL) and C. maritima lectin (CML) complexed with Man(α1-2)Man(α1)OMe, Man(α1-3)Man(α1)OMe and Man(α1-4)Man(α1)OMe in two crystal forms [the complexes with Man(α1-3)Man(α1)OMe and Man(α1-4)Man(α1)OMe crystallized in space group P3{sub 2} and those with Man(α1-2)Man(α1)OMe crystallized in space group I222], which differed from those of the native proteins (P2{sub 1}2{sub 1}2 for CML and C222 for CGL), are reported. The crystal complexes of ConA-like lectins with Man(α1-4)Man(α1)OMe are reported here for the first time.« less

NCBI disease corpus: a resource for disease name recognition and concept normalization.

PubMed

Doğan, Rezarta Islamaj; Leaman, Robert; Lu, Zhiyong

2014-02-01

Information encoded in natural language in biomedical literature publications is only useful if efficient and reliable ways of accessing and analyzing that information are available. Natural language processing and text mining tools are therefore essential for extracting valuable information, however, the development of powerful, highly effective tools to automatically detect central biomedical concepts such as diseases is conditional on the availability of annotated corpora. This paper presents the disease name and concept annotations of the NCBI disease corpus, a collection of 793 PubMed abstracts fully annotated at the mention and concept level to serve as a research resource for the biomedical natural language processing community. Each PubMed abstract was manually annotated by two annotators with disease mentions and their corresponding concepts in Medical Subject Headings (MeSH®) or Online Mendelian Inheritance in Man (OMIM®). Manual curation was performed using PubTator, which allowed the use of pre-annotations as a pre-step to manual annotations. Fourteen annotators were randomly paired and differing annotations were discussed for reaching a consensus in two annotation phases. In this setting, a high inter-annotator agreement was observed. Finally, all results were checked against annotations of the rest of the corpus to assure corpus-wide consistency. The public release of the NCBI disease corpus contains 6892 disease mentions, which are mapped to 790 unique disease concepts. Of these, 88% link to a MeSH identifier, while the rest contain an OMIM identifier. We were able to link 91% of the mentions to a single disease concept, while the rest are described as a combination of concepts. In order to help researchers use the corpus to design and test disease identification methods, we have prepared the corpus as training, testing and development sets. To demonstrate its utility, we conducted a benchmarking experiment where we compared three different knowledge-based disease normalization methods with a best performance in F-measure of 63.7%. These results show that the NCBI disease corpus has the potential to significantly improve the state-of-the-art in disease name recognition and normalization research, by providing a high-quality gold standard thus enabling the development of machine-learning based approaches for such tasks. The NCBI disease corpus, guidelines and other associated resources are available at: http://www.ncbi.nlm.nih.gov/CBBresearch/Dogan/DISEASE/. Published by Elsevier Inc.

Distributed medical services within the ATM-based Berlin regional test bed

NASA Astrophysics Data System (ADS)

Thiel, Andreas; Bernarding, Johannes; Krauss, Manfred; Schulz, Sandra; Tolxdorff, Thomas

1996-05-01

The ATM-based Metropolitan Area Network (MAN) of Berlin connects two university hospitals (Benjamin Franklin University Hospital and Charite) with the computer resources of the Technical University of Berlin (TUB). Distributed new medical services have been implemented and will be evaluated within the highspeed MAN of Berlin. The network with its data transmission rates of up to 155 Mbit/s renders these medical services externally available to practicing physicians. Resource and application sharing is demonstrated by the use of two software systems. The first software system is an interactive 3D reconstruction tool (3D- Medbild), based on a client-server mechanism. This structure allows the use of high- performance computers at the TUB from the low-level workstations in the hospitals. A second software system, RAMSES, utilizes a tissue database of Magnetic Resonance Images. For the remote control of the software, the developed applications use standards such as DICOM 3.0 and features of the World Wide Web. Data security concepts are being tested and integrated for the needs of the sensitive medical data. The highspeed network is the necessary prerequisite for the clinical evaluation of data in a joint teleconference. The transmission of digitized real-time sequences such as video and ultrasound and the interactive manipulation of data are made possible by Multi Media tools.

Application of 3-D Urbanization Index to Assess Impact of Urbanization on Air Temperature

NASA Astrophysics Data System (ADS)

Wu, Chih-Da; Lung, Shih-Chun Candice

2016-04-01

The lack of appropriate methodologies and indicators to quantify three-dimensional (3-D) building constructions poses challenges to authorities and urban planners when formulating polices to reduce health risks due to heat stress. This study evaluated the applicability of an innovative three-dimensional Urbanization Index (3DUI), based on remote sensing database, with a 5 m spatial resolution of 3-D man-made constructions to representing intra-urban variability of air temperature by assessing correlation of 3DUI with air temperature from a 3-D perspective. The results showed robust high correlation coefficients, ranging from 0.83 to 0.85, obtained within the 1,000 m circular buffer around weather stations regardless of season, year, or spatial location. Our findings demonstrated not only the strength of 3DUI in representing intra-urban air-temperature variability, but also its great potential for heat stress assessment within cities. In view of the maximum correlation between building volumes within the 1,000 m circular buffer and ambient air temperature, urban planning should consider setting ceilings for man-made construction volume in each 2 × 2 km2 residential community for thermal environment regulation, especially in Asian metropolis with high population density in city centers.

Application of 3-D Urbanization Index to Assess Impact of Urbanization on Air Temperature

PubMed Central

Wu, Chih-Da; Lung, Shih-Chun Candice

2016-01-01

The lack of appropriate methodologies and indicators to quantify three-dimensional (3-D) building constructions poses challenges to authorities and urban planners when formulating polices to reduce health risks due to heat stress. This study evaluated the applicability of an innovative three-dimensional Urbanization Index (3DUI), based on remote sensing database, with a 5 m spatial resolution of 3-D man-made constructions to representing intra-urban variability of air temperature by assessing correlation of 3DUI with air temperature from a 3-D perspective. The results showed robust high correlation coefficients, ranging from 0.83 to 0.85, obtained within the 1,000 m circular buffer around weather stations regardless of season, year, or spatial location. Our findings demonstrated not only the strength of 3DUI in representing intra-urban air-temperature variability, but also its great potential for heat stress assessment within cities. In view of the maximum correlation between building volumes within the 1,000 m circular buffer and ambient air temperature, urban planning should consider setting ceilings for man-made construction volume in each 2 × 2 km2 residential community for thermal environment regulation, especially in Asian metropolis with high population density in city centers. PMID:27079537

Acupuncture for common cold: A systematic review and meta-analyze protocol.

PubMed

Cheng, Ying; Gao, Bifeng; Jin, Yuhao; Xu, Na; Guo, Taipin

2018-03-01

The common cold (CC) is the most common syndromes of infection in human beings, but there is currently no special treatment. For this reason, acupuncture is used to relieve the symptoms of the CC. Acupuncture is a traditional Chinese medicine (TCM) therapy that has been used for over 2000 years to treat various diseases. However, few studies have provided evidence for the efficacy and safety of acupuncture for the CC. This study aims to evaluate the effectiveness and safety of acupuncture on CC periods and its symptoms. The following electronic databases will be searched for studies conducted through January 1, 2019: Web of Science, Cochrane Library, EBASE, World Health Organization International Clinical Trials Registry Platform, Springer, Wan-fang database, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP), China National Knowledge Infrastructure (CNKI), and other sources. All randomized controlled trials on acupuncture for common cold will be included. Risk of bias will be assessed using the Cochrane risk of bias assessment tool, while RevMan V.5.3.5 software will be implemented for the assessment of bias risk, data synthesis, subgroup analysis, and meta-analyses if conditions are met. Continuous outcomes will be presented as mean difference (MD) or standard mean difference (SMD), while dichotomous data will be expressed as relative risk. A high-quality synthesis of current evidence of acupuncture for CC will be stated from several aspect using subjective reports and objective measures of performance. The reduction rate of common cold symptoms after initial treatment, resolved cold symptoms, and reduced cold duration will be collected. This protocol will present the evidence of whether acupuncture therapy is an effective intervention for CC.

Geolocation of man-made reservoirs across terrains of varying complexity using GIS

USGS Publications Warehouse

Mixon, D.M.; Kinner, D.A.; Stallard, R.F.; Syvitski, J.P.M.

2008-01-01

The Reservoir Sedimentation Survey Information System (RESIS) is one of the world's most comprehensive databases of reservoir sedimentation rates, comprising nearly 6000 surveys for 1819 reservoirs across the continental United States. Sediment surveys in the database date from 1904 to 1999, though more than 95% of surveys were entered prior to 1980, making RESIS largely a historical database. The use of this database for large-scale studies has been limited by the lack of precise coordinates for the reservoirs. Many of the reservoirs are relatively small structures and do not appear on current USGS topographic maps. Others have been renamed or have only approximate (i.e. township and range) coordinates. This paper presents a method scripted in ESRI's ARC Macro Language (AML) to locate the reservoirs on digital elevation models using information available in RESIS. The script also delineates the contributing watersheds and compiles several hydrologically important parameters for each reservoir. Evaluation of the method indicates that, for watersheds larger than 5 km2, the correct outlet is identified over 80% of the time. The importance of identifying the watershed outlet correctly depends on the application. Our intent is to collect spatial data for watersheds across the continental United States and describe the land use, soils, and topography for each reservoir's watershed. Because of local landscape similarity in these properties, we show that choosing the incorrect watershed does not necessarily mean that the watershed characteristics will be misrepresented. We present a measure termed terrain complexity and examine its relationship to geolocation success rate and its influence on the similarity of nearby watersheds. ?? 2008 Elsevier Ltd. All rights reserved.

Crew activity and motion effects on the space station

NASA Technical Reports Server (NTRS)

Rochon, Brian V.; Scheer, Steven A.

1987-01-01

Among the significant sources of internal disturbances that must be considered in the design of space station vibration control systems are the loads induced on the structure from various crew activities. Flight experiment T013, flown on the second manned mission of Skylab, measured force and moment time histories for a range of preplanned crew motions and activities. This experiment has proved itself invaluable as a source of on-orbit crew induced loads that has allowed a space station forcing function data base to be built. This will enable forced response such as acceleration and deflections, attributable to crew activity, to be calculated. The flight experiment, resultant database and structural model pre-processor, analysis examples and areas of combined research shall be described.

A Danish family with dominant deafness-onychodystrophy syndrome.

PubMed

Vind-Kezunovic, Dina; Torring, Pernille M

2013-01-01

The rare hereditary disorder "dominant deafness and onychodystrophy (DDOD) syndrome" (OMIM 124480) has been described in a few case reports. No putative DDOD gene or locus has been mapped and the cause of the disorder remains unknown. We present here three male family members in three generations with sensori-neural deafness, onychodystrophy and brachydactyly inherited via autosomal dominant transmission. The family members presented with absent fingernails on the first and fifth digits. As to the feet, there were absent nails on second to fifth toes in two family members, whereas the third family member only had absent nails on the fifth toe. The proband had late dentition and his father a history of late dentition, but otherwise the teeth appeared normal. Comparative genomic hybridization array analysis (Agilent 400k oligoarray) of the proband did not detect any copy number variation. This Danish family fits within the spectrum of dominant deafness and onychodystrophy syndrome and further characterises this rare disorder.

Identification of novel mutations in Mexican patients with Aarskog-Scott syndrome.

PubMed

Pérez-Coria, Mariana; Lugo-Trampe, José J; Zamudio-Osuna, Michell; Rodríguez-Sánchez, Iram P; Lugo-Trampe, Angel; de la Fuente-Cortez, Beatriz; Campos-Acevedo, Luis D; Martínez-de-Villarreal, Laura E

2015-05-01

Aarskog-Scott syndrome (AAS), also known as faciogenital dysplasia (FGD, OMIM # 305400), is an X-linked disorder of recessive inheritance, characterized by short stature and facial, skeletal, and urogenital abnormalities. AAS is caused by mutations in the FGD1 gene (Xp11.22), with over 56 different mutations identified to date. We present the clinical and molecular analysis of four unrelated families of Mexican origin with an AAS phenotype, in whom FGD1 sequencing was performed. This analysis identified two stop mutations not previously reported in the literature: p.Gln664* and p.Glu380*. Phenotypically, every male patient met the clinical criteria of the syndrome, whereas discrepancies were found between phenotypes in female patients. Our results identify two novel mutations in FGD1, broadening the spectrum of reported mutations; and provide further delineation of the phenotypic variability previously described in AAS.

Identification of novel mutations in Mexican patients with Aarskog–Scott syndrome

PubMed Central

Pérez-Coria, Mariana; Lugo-Trampe, José J; Zamudio-Osuna, Michell; Rodríguez-Sánchez, Iram P; Lugo-Trampe, Angel; de la Fuente-Cortez, Beatriz; Campos-Acevedo, Luis D; Martínez-de-Villarreal, Laura E

2015-01-01

Aarskog–Scott syndrome (AAS), also known as faciogenital dysplasia (FGD, OMIM # 305400), is an X-linked disorder of recessive inheritance, characterized by short stature and facial, skeletal, and urogenital abnormalities. AAS is caused by mutations in the FGD1 gene (Xp11.22), with over 56 different mutations identified to date. We present the clinical and molecular analysis of four unrelated families of Mexican origin with an AAS phenotype, in whom FGD1 sequencing was performed. This analysis identified two stop mutations not previously reported in the literature: p.Gln664* and p.Glu380*. Phenotypically, every male patient met the clinical criteria of the syndrome, whereas discrepancies were found between phenotypes in female patients. Our results identify two novel mutations in FGD1, broadening the spectrum of reported mutations; and provide further delineation of the phenotypic variability previously described in AAS. PMID:26029706

Treacher Collins syndrome: New insights from animal models.

PubMed

Tse, William Ka Fai

2016-12-01

Treacher Collins syndrome (TCS, OMIM: 154500), an autosomal-dominant craniofacial developmental syndrome that occurs in 1 out of every 50,000 live births, is characterized by craniofacial malformation. Mutations in TCOF1, POLR1C, or POLR1D have been identified in affected individuals. In addition to established mouse models, zebrafish models have recently emerged as an valuable method to study facial disease. In this report, we summarized the two updated articles working on the pathogenesis of the newly identified polr1c and polr1d TCS mutations (Lau et al., 2016; Noack Watt et al., 2016) and discussed the possibility of using the anti-oxidants to prevent or rescue the TCS facial phenotype (Sakai et al., 2016). Taken together, this article provides an update on the disease from basic information to pathogenesis, and further summarizes the suggested therapies from recent laboratory research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bartter Syndrome Type 1 Presenting as Nephrogenic Diabetes Insipidus

PubMed Central

Fabbri, Elena; Pedini, Annalisa; Tedeschi, Silvana; Borsa, Niccolò

2018-01-01

Bartter syndrome (BS) type 1 (OMIM #601678) is a hereditary salt-losing renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, polyuria, recurrent vomiting, and growth retardation. It is caused by loss-of-function mutations of the SLC12A1 gene, encoding the furosemide-sensitive Na-K-Cl cotransporter. Recently, a phenotypic variability has been observed in patients with genetically determined BS, including absence of nephrocalcinosis, hypokalemia, and/or metabolic alkalosis in the first year of life as well as persistent metabolic acidosis mimicking distal renal tubular acidosis. We report the case of a child with a genetically determined diagnosis of Bartter syndrome type 1 who presented with a phenotype of nephrogenic diabetes insipidus, with severe hypernatremia and urinary concentrating defect. In these atypical cases, molecular analysis is mandatory to define the diagnosis, in order to establish the correct clinical and therapeutic management. PMID:29527380

Bartter Syndrome Type 1 Presenting as Nephrogenic Diabetes Insipidus.

PubMed

Vergine, Gianluca; Fabbri, Elena; Pedini, Annalisa; Tedeschi, Silvana; Borsa, Niccolò

2018-01-01

Bartter syndrome (BS) type 1 (OMIM #601678) is a hereditary salt-losing renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, polyuria, recurrent vomiting, and growth retardation. It is caused by loss-of-function mutations of the SLC12A1 gene, encoding the furosemide-sensitive Na-K-Cl cotransporter. Recently, a phenotypic variability has been observed in patients with genetically determined BS, including absence of nephrocalcinosis, hypokalemia, and/or metabolic alkalosis in the first year of life as well as persistent metabolic acidosis mimicking distal renal tubular acidosis. We report the case of a child with a genetically determined diagnosis of Bartter syndrome type 1 who presented with a phenotype of nephrogenic diabetes insipidus, with severe hypernatremia and urinary concentrating defect. In these atypical cases, molecular analysis is mandatory to define the diagnosis, in order to establish the correct clinical and therapeutic management.

A locus for cerebral cavernous malformations maps to chromosome 7q in two families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchuk, D.A.; Gallione, C.J.; Morrison, L.A.

1995-07-20

Cavernous malformations (angiomas) affecting the central nervous system and retina can be inherited in autosomal dominant pattern (OMIM 116860). These vascular lesions may remain clinically silent or lead to a number of neurological symptoms including seizure, intracranial hemorrhage, focal neurological deficit, and migraine. We have mapped a gene for this disorder in two families, one of Italian-American origin and one of Mexican-American origin, to markers on proximal 7q, with a combined maximum lod score of 3.92 ({theta} of zero) with marker D7S479. Haplotype analysis of these families places the locus between markers D7S502 proximally and D7S515 distally, an interval ofmore » approximately 41 cM. The location distinguishes this disorder from an autosomal dominant vascular malformation syndrome where lesions are primarily cutaneous and that maps to 9p21. 16 refs., 3 figs., 1 tab.« less

Lewis-Sumner syndrome and Tangier disease.

PubMed

Théaudin, Marie; Couvert, Philippe; Fournier, Emmanuel; Bouige, Daniel; Bruckert, Eric; Perrotte, Paul; Vaschalde, Yvan; Maisonobe, Thierry; Bonnefont-Rousselot, Dominique; Carrié, Alain; Le Forestier, Nadine

2008-07-01

To report unusual electrophysiologic data in a patient with Tangier disease in an effort to better understand the pathophysiologic features of the peripheral nerve lesions in this disease. Case report. A 15-year-old girl had subacute onset of asymmetric neuropathy with persistent conduction block, resembling Lewis-Sumner syndrome. Electrophysiologic data in Tangier disease. After initially unsuccessful treatment with intravenously administered immunoglobulins, the finding of an abnormal lipid profile led to the diagnosis of Tangier disease due to the R587W mutation in the adenotriphosphate-binding cassette transporter-1 gene (ABCA1) (OMIM 9q22-q31). Conduction block, which is the electrophysiologic hallmark of focal demyelination, can be present in Tangier disease. It could be induced by focal nerve ischemia or by preferential lipid deposition in the paranodal regions of myelinated Schwann cells. The presence of a conduction block in Tangier disease may lead to a misdiagnosis of dysimmune neuropathy.

Leveraging terminological resources for mapping between rare disease information sources.

PubMed

Rance, Bastien; Snyder, Michelle; Lewis, Janine; Bodenreider, Olivier

2013-01-01

Rare disease information sources are incompletely and inconsistently cross-referenced to one another, making it difficult for information seekers to navigate across them. The development of such cross-references established manually by experts is generally labor intensive and costly. To develop an automatic mapping between two of the major rare diseases information sources, GARD and Orphanet, by leveraging terminological resources, especially the UMLS. We map the rare disease terms from Orphanet and ORDR to the UMLS. We use the UMLS as a pivot to bridge between the rare disease terminologies. We compare our results to a mapping obtained through manually established cross-references to OMIM. Our mapping has a precision of 94%, a recall of 63% and an F1-score of 76%. Our automatic mapping should help facilitate the development of more complete and consistent cross-references between GARD and Orphanet, and is applicable to other rare disease information sources as well.

Language disorder with mild intellectual disability in a child affected by a novel mutation of SLC6A8 gene.

PubMed

Battini, R; Chilosi, A M; Casarano, M; Moro, F; Comparini, A; Alessandrì, M G; Leuzzi, V; Tosetti, M; Cioni, G

2011-02-01

We describe the clinical and molecular features of a child harboring a novel mutation in SLC6A8 gene in association with a milder phenotype than other creatine transporter (CT1) deficient patients (OMIM 300352) [1-7]. The mutation c.757 G>C p.G253R in exon 4 of SLC6A8 was hemizygous in the child, aged 6 years and 6 months, who showed mild intellectual disability with severe speech and language delay. His carrier mother had borderline intellectual functioning. Although the neurochemical and biochemical parameters were fully consistent with those reported in the literature for subjects with CT1 deficit, in our patient within a general cognitive disability, a discrepancy between nonverbal and verbal skills was observed, confirming the peculiar vulnerability of language development under brain Cr depletion. Copyright © 2010 Elsevier Inc. All rights reserved.

Germinal mosaicism in Noonan syndrome: A family with two affected siblings of normal parents.

PubMed

Elalaoui, Siham Chafai; Kraoua, Lilia; Liger, Céline; Ratbi, Ilham; Cavé, Hélène; Sefiani, Abdelaziz

2010-11-01

Noonan syndrome (NS; OMIM 163950) is an autosomal dominant disorder with variable clinical expression and genetic heterogeneity. Clinical manifestations include characteristic facial features, short stature, and cardiac anomalies. Mutations in protein-tyrosine phosphatase, non-receptor-type 11 (PTPN11), encoding SHP-2, account for about half of NS patients. We report on a Moroccan family with two children with NS and apparently unaffected parents. The molecular studies showed the heterozygous mutation c.922A>G of PTPN11 gene in the two affected sibs. Neither the parents, nor the oldest brother carries this mutation in hematologic cells. The mutation was also absent in buccal epithelial cells and fingernails of both parents. We believe this is the first report of germ cell mosaicism in NS and suggest an empirical risk for recurrence of that is less than 1%. © 2010 Wiley-Liss, Inc.

The first familial case of inherited 2q37.3 interstitial deletion with isolated skeletal abnormalities including brachydactyly type E and short stature.

PubMed

Jean-Marçais, Nolwenn; Decamp, Matthieu; Gérard, Marion; Ribault, Virginie; Andrieux, Joris; Kottler, Marie-Laure; Plessis, Ghislaine

2015-01-01

Albright hereditary osteodystrophy (AHO)-like syndrome is also known as brachydactyly-mental retardation syndrome (BDMR; OMIM 60040). This disorder includes intellectual disability in all patients, skeletal abnormalities, including brachydactyly E (BDE) in approximately half, obesity, and facial dysmorphism. Patients with 2q37 microdeletion or HDAC4 mutation are defined as having an AHO-like phenotype with normal stimulatory G (Gs) function. HDAC4 is involved in neurological, cardiac, and skeletal function. This paper reports the first familial case of 2q37.3 interstitial deletion affecting two genes, HDAC4 and TWIST2. Patients presented with BDE and short stature without intellectual disability, showing that haploinsufficiency of the HDAC4 critical region may lead to a spectrum of phenotypes, ranging from isolated brachydactyly type E to BDMR. © 2014 Wiley Periodicals, Inc.

Association of a Novel Nonsense Mutation in KIAA1279 with Goldberg-Shprintzen Syndrome.

PubMed

Salehpour, Shadab; Hashemi-Gorji, Feyzollah; Soltani, Ziba; Ghafouri-Fard, Soudeh; Miryounesi, Mohammad

2017-01-01

Goldberg-Shprintzen syndrome (OMIM 609460) (GOSHS) is an autosomal recessive multiple congenital anomaly syndrome distinguished by intellectual disability, microcephaly, and dysmorphic facial characteristics. Most affected individuals also have Hirschsprung disease and/or gyral abnormalities of the brain. This syndrome has been associated with KIAA1279 gene mutations at 10q22.1. Here we report a 16 yr old male patient referred to Center for Comprehensive Genetic Services, Tehran, Iran in 2015 with cardinal features of GOSHS in addition to refractory seizures. Whole exome sequencing in the patient revealed a novel nonsense (stop gain) homozygous mutation in KIAA1279 gene (KIAA1279: NM_015634:exon6:c.C976T:p.Q326X). Considering the wide range of phenotypic variations in GOSHS, relying on phenotypic characteristics for discrimination of GOSH from similar syndromes may lead to misdiagnosis. Consequently, molecular diagnostic tools would help in accurate diagnosis of such overlapping phenotypes.

[Prolonged neuromuscular block in a patient with butyrylcholinesterase deficiency].

PubMed

Mabboux, I; Hary, B; Courcelle, S; Ceppa, F; Delacour, H

2016-05-01

Succinylcholine is a neuromuscular block whose duration of action depends on rapid hydrolysis by butyrylcholinesterase (BChE). In patients with common BChE activities, succinylcholine duration of action is short (10min). BChE deficiency induces a slower hydrolysis of the drug and consequently prolonged neuromuscular block, leading to apnea. We report a case of prolonged neuromuscular block after administration of succinylcholine in a 14-year-old boy. Biological investigations revealed a marked BChE deficiency (1099U/L) related to the presence of three point mutations in the BCHE gene in a compound heterozygous state: p.Asp70Gly (rs1799807), p.Ala539Tyr (rs1803274), and p.Phe118Valfs*12 (rs398124632). The diagnosis of genetic BChE deficiency (OMIM 177400) was retained. This case is intended to present the pathophysiology of genetic BChE deficiency, its management, and the diagnostic strategy to be implemented. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Enzyme Mini-Test for Field Identification of Leishmania Isolates from U.S. Military Personnel.

DTIC Science & Technology

1986-05-15

Panama Dominques L2 539 NWC LBP Man - Panama Carillo 530 NWC LBP Man - Panama Schoonmaker 063 NWC LBG Man - Peru Terborgh/Muco 294 NWC LBB Man - Brazil...NWC LMA-G Man - Panama Castro 140 NWC LMM-P Man - Peru UTA 381 NWC LMM-P Man - Panama Peters 453 NWC LMM-P Man - Dominican Republic - 457 NWC LMM-P...LV24 547 OWC LMJ Man R. Beach Kenya LRC-L137 551 OWC LMJ Rodent R. Beach Kenya NLB095 552 OWC LMJ Sandfly R. Beach Kenya NLBI44 558 OWC LMJ Man

[Effect of premolar extractions on third molar angulation changes: a meta-analysis].

PubMed

Fan, Linlin; Kuang, Qin; Tang, Yujuan; Qin, Pu

2015-03-01

To assess the effect of premolar extractions on third molar angulation changes in orthodontic patients. The Cochrane library, PubMed, Embase, China Science and Technology Periodical Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Wanfang database were searched from January 1, 1990 to May 20, 2014 to identify all the studies about third molar angulation changes in orthodontic patients with or without premolars extraction, which was assigned as a extraction group and a control group. Th e extraction group was further divided into a fi rst premolar extraction subgroup and a second premolar extraction subgroup. Literature filtering, data extraction and methodological quality evaluation were finished independently by two researchers. After cross checking, the disagreements were solved by discussion. Meta-analysis was carried out by RevMan 5.3.3 software. Ten studies involving 712 patients were included. Meta-analysis revealed that: compared with the control group, the changes of third molar angulation in maxillary and mandible in the extraction group were statistically significantly different (all P<0.05); the difference in angulation between the two groups was about 5.19° in maxillary and 3.55° in mandibul. As for the premolar extraction subgroups, there was no significant difference in mandibular third molar angulation between them (P>0.05). The orthodontic treatment involving first or second premolar extractions can improve the maxillary third molar angulation, and the second premolar extraction is the best option.

Human phoneme recognition depending on speech-intrinsic variability.

PubMed

Meyer, Bernd T; Jürgens, Tim; Wesker, Thorsten; Brand, Thomas; Kollmeier, Birger

2010-11-01

The influence of different sources of speech-intrinsic variation (speaking rate, effort, style and dialect or accent) on human speech perception was investigated. In listening experiments with 16 listeners, confusions of consonant-vowel-consonant (CVC) and vowel-consonant-vowel (VCV) sounds in speech-weighted noise were analyzed. Experiments were based on the OLLO logatome speech database, which was designed for a man-machine comparison. It contains utterances spoken by 50 speakers from five dialect/accent regions and covers several intrinsic variations. By comparing results depending on intrinsic and extrinsic variations (i.e., different levels of masking noise), the degradation induced by variabilities can be expressed in terms of the SNR. The spectral level distance between the respective speech segment and the long-term spectrum of the masking noise was found to be a good predictor for recognition rates, while phoneme confusions were influenced by the distance to spectrally close phonemes. An analysis based on transmitted information of articulatory features showed that voicing and manner of articulation are comparatively robust cues in the presence of intrinsic variations, whereas the coding of place is more degraded. The database and detailed results have been made available for comparisons between human speech recognition (HSR) and automatic speech recognizers (ASR).

Large Dosage of Chishao in Formulae for Cholestatic Hepatitis: A Systematic Review and Meta-Analysis

PubMed Central

Ma, Xiao; Wang, Ji; He, Xuan; Zhao, Yanling; Wang, Jiabo; Zhang, Ping; Zhu, Yun; Zhong, Lin; Zheng, Quanfu; Xiao, Xiaohe

2014-01-01

Objective. To evaluate the efficacy and safety of large dosage of Chishao in formulae for treatment of cholestatic hepatitis. Methods. The major databases (PubMed, Embase, Cochrane Library, Chinese Biomedical Database Wanfang, VIP medicine information system, and China National Knowledge Infrastructure) were searched until January 2014. Randomized controlled trials (RCTs) of large dosage of Chishao in formulae that reported on publications in treatment of cholestatic hepatitis with total efficacy rate, together with the biochemical indices including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), were extracted by two reviewers. The Cochrane tool was used for the assessment of risk of bias included trials. Data were analyzed with RevMan 5.2.7 software. Results. 11 RCTs involving 1275 subjects with cholestatic hepatitis were included. Compared with essential therapy, large dosage of Chishao in formulae demonstrated more efficiently with down regulation of serum ALT, AST, TBIL, DBIL. Meanwhile, there were no obvious adverse events. Conclusion. As a promising novel treatment approach, widely using large dosage of Chishao in formulae may enhance the curative efficacy for cholestatic hepatitis. Considering being accepted by more and more practitioners, further rigorously designed clinical studies are required. PMID:24987427

Aberrant signature methylome by DNMT1 hot spot mutation in hereditary sensory and autonomic neuropathy 1E.

PubMed

Sun, Zhifu; Wu, Yanhong; Ordog, Tamas; Baheti, Saurabh; Nie, Jinfu; Duan, Xiaohui; Hojo, Kaori; Kocher, Jean-Pierre; Dyck, Peter J; Klein, Christopher J

2014-08-01

DNA methyltransferase 1 (DNMT1) is essential for DNA methylation, gene regulation and chromatin stability. We previously discovered DNMT1 mutations cause hereditary sensory and autonomic neuropathy type 1 with dementia and hearing loss (HSAN1E; OMIM 614116). HSAN1E is the first adult-onset neurodegenerative disorder caused by a defect in a methyltransferase gene. HSAN1E patients appear clinically normal until young adulthood, then begin developing the characteristic symptoms involving central and peripheral nervous systems. Some HSAN1E patients also develop narcolepsy and it has recently been suggested that HSAN1E is allelic to autosomal dominant cerebellar ataxia, deafness, with narcolepsy (ADCA-DN; OMIM 604121), which is also caused by mutations in DNMT1. A hotspot mutation Y495C within the targeting sequence domain of DNMT1 has been identified among HSAN1E patients. The mutant DNMT1 protein shows premature degradation and reduced DNA methyltransferase activity. Herein, we investigate genome-wide DNA methylation at single-base resolution through whole-genome bisulfite sequencing of germline DNA in 3 pairs of HSAN1E patients and their gender- and age-matched siblings. Over 1 billion 75-bp single-end reads were generated for each sample. In the 3 affected siblings, overall methylation loss was consistently found in all chromosomes with X and 18 being most affected. Paired sample analysis identified 564,218 differentially methylated CpG sites (DMCs; P<0.05), of which 300 134 were intergenic and 264 084 genic CpGs. Hypomethylation was predominant in both genic and intergenic regions, including promoters, exons, most CpG islands, L1, L2, Alu, and satellite repeats and simple repeat sequences. In some CpG islands, hypermethylated CpGs outnumbered hypomethylated CpGs. In 201 imprinted genes, there were more DMCs than in non-imprinted genes and most were hypomethylated. Differentially methylated region (DMR) analysis identified 5649 hypomethylated and 1872 hypermethylated regions. Importantly, pathway analysis revealed 1693 genes associated with the identified DMRs were highly associated in diverse neurological disorders and NAD+/NADH metabolism pathways is implicated in the pathogenesis. Our results provide novel insights into the epigenetic mechanism of neurodegeneration arising from a hotspot DNMT1 mutation and reveal pathways potentially important in a broad category of neurological and psychological disorders.

Aberrant signature methylome by DNMT1 hot spot mutation in hereditary sensory and autonomic neuropathy 1E

PubMed Central

Sun, Zhifu; Wu, Yanhong; Ordog, Tamas; Baheti, Saurabh; Nie, Jinfu; Duan, Xiaohui; Hojo, Kaori; Kocher, Jean-Pierre; Dyck, Peter J; Klein, Christopher J

2014-01-01

DNA methyltransferase 1 (DNMT1) is essential for DNA methylation, gene regulation and chromatin stability. We previously discovered DNMT1 mutations cause hereditary sensory and autonomic neuropathy type 1 with dementia and hearing loss (HSAN1E; OMIM 614116). HSAN1E is the first adult-onset neurodegenerative disorder caused by a defect in a methyltransferase gene. HSAN1E patients appear clinically normal until young adulthood, then begin developing the characteristic symptoms involving central and peripheral nervous systems. Some HSAN1E patients also develop narcolepsy and it has recently been suggested that HSAN1E is allelic to autosomal dominant cerebellar ataxia, deafness, with narcolepsy (ADCA-DN; OMIM 604121), which is also caused by mutations in DNMT1. A hotspot mutation Y495C within the targeting sequence domain of DNMT1 has been identified among HSAN1E patients. The mutant DNMT1 protein shows premature degradation and reduced DNA methyltransferase activity. Herein, we investigate genome-wide DNA methylation at single-base resolution through whole-genome bisulfite sequencing of germline DNA in 3 pairs of HSAN1E patients and their gender- and age-matched siblings. Over 1 billion 75-bp single-end reads were generated for each sample. In the 3 affected siblings, overall methylation loss was consistently found in all chromosomes with X and 18 being most affected. Paired sample analysis identified 564,218 differentially methylated CpG sites (DMCs; P < 0.05), of which 300 134 were intergenic and 264 084 genic CpGs. Hypomethylation was predominant in both genic and intergenic regions, including promoters, exons, most CpG islands, L1, L2, Alu, and satellite repeats and simple repeat sequences. In some CpG islands, hypermethylated CpGs outnumbered hypomethylated CpGs. In 201 imprinted genes, there were more DMCs than in non-imprinted genes and most were hypomethylated. Differentially methylated region (DMR) analysis identified 5649 hypomethylated and 1872 hypermethylated regions. Importantly, pathway analysis revealed 1693 genes associated with the identified DMRs were highly associated in diverse neurological disorders and NAD+/NADH metabolism pathways is implicated in the pathogenesis. Our results provide novel insights into the epigenetic mechanism of neurodegeneration arising from a hotspot DNMT1 mutation and reveal pathways potentially important in a broad category of neurological and psychological disorders. PMID:25033457

Oto-facial syndrome and esophageal atresia, intellectual disability and zygomatic anomalies - expanding the phenotypes associated with EFTUD2 mutations

PubMed Central

2013-01-01

Background Mutations in EFTUD2 were proven to cause a very distinct mandibulofacial dysostosis type Guion-Almeida (MFDGA, OMIM #610536). Recently, gross deletions and mutations in EFTUD2 were determined to cause syndromic esophageal atresia (EA), as well. We set forth to find further conditions caused by mutations in the EFTUD2 gene (OMIM *603892). Methods and results We performed exome sequencing in two familial cases with clinical features overlapping with MFDGA and EA, but which were previously assumed to represent distinct entities, a syndrome with esophageal atresia, hypoplasia of zygomatic complex, microcephaly, cup-shaped ears, congenital heart defect, and intellectual disability in a mother and her two children [AJMG 143A(11):1135-1142, 2007] and a supposedly autosomal recessive oto-facial syndrome with midline malformations in two sisters [AJMG 132(4):398-401, 2005]. While the analysis of our exome data was in progress, a recent publication made EFTUD2 mutations highly likely in these families. This hypothesis could be confirmed with exome as well as with Sanger sequencing. Also, in three further sporadic patients, clinically overlapping to these two families, de novo mutations within EFTUD2 were identified by Sanger sequencing. Our clinical and molecular workup of the patients discloses a broad phenotypic spectrum, and describes for the first time an instance of germline mosaicism for an EFTUD2 mutation. Conclusions The clinical features of the eight patients described here further broaden the phenotypic spectrum caused by EFTUD2 mutations or deletions. We here show, that it not only includes mandibulofacial dysostosis type Guion-Almeida, which should be reclassified as an acrofacial dysostosis because of thumb anomalies (present in 12/35 or 34% of patients) and syndromic esophageal atresia [JMG 49(12). 737-746, 2012], but also the two new syndromes, namely oto-facial syndrome with midline malformations published by Mégarbané et al. [AJMG 132(4): 398-401, 2005] and the syndrome published by Wieczorek et al. [AJMG 143A(11): 1135-1142, 2007] The finding of mild phenotypic features in the mother of one family that could have been overlooked and the possibility of germline mosaicism in apparently healthy parents in the other family should be taken into account when counseling such families. PMID:23879989

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family.

PubMed

Galantuomo, Maria Silvana; Fossarello, Maurizio; Cuccu, Alberto; Farci, Roberta; Preising, Markus N; Lorenz, Birgit; Napoli, Pietro Emanuele

2016-01-01

Juvenile X-linked retinoschisis (RS1, OMIM: 312700) is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments. The purposes of this study were to present, for the first time, a p.Arg197Cys missense mutation in the RS1 gene (OMIM: 300839) in a four-generation Italian family with RS1 and to examine the clinical response to the treatment with acetazolamide tablets alone or in combination with dorzolamide eye drops as assessed by spectral-domain optical coherence tomography (SD-OCT). Eleven individuals, including two brothers with RS1 (patients 1 and 2), underwent a full medical history examination and a comprehensive ocular assessment that involved SD-OCT, fluorescein angiography, electroretinography and DNA analysis. Each RS1 patient received oral acetazolamide (375 mg daily) during the first three months. Thereafter, patient 1 continued only with dorzolamide eyedrops three times a day for a period of three months, while patient 2 spontaneously stopped both medications. Sequence analysis of the RS1 gene identified a hemizygous c.589C>T (p.Arg197Cys) missense mutation in exon 6, which has not been previously reported in an Italian family. A different response to the medical therapy was observed in the four eyes of the two affected brothers hemizygous for this abnormality. Of note, after acetazolamide interruption, a rebound effect on cystoid macular edema reduced the beneficial effects of the initial therapy for RS1 from p.Arg197Cys mutation. Indeed, a minimal rebound effect on cystoid macular edema, and an improvement in visual acuity, was observed in patient 1 during the six months of treatment. Conversely, in patient 2, an initial improvement in cystoid macular edema was not associated with visual acuity changes, followed by a marked rebound effect. This study showed that the sequential use of acetazolamide tablets and dorzolamide eye drops should be considered and studied further as a possible treatment for macular edema and visual impairment in patients with RS1 from a hemizygous p.Arg197Cys mutation.

76 FR 15366 - Additional Designation of Entities Pursuant to Executive Order 13382

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-21

..., Manning House, 21 Bucks Road, Douglas IM1 3DA, Man, Isle of; Business Registration Document 003648V (Man..., Man, Isle of; Business Registration Document 003645V (Man, Isle of) issued 2 Mar 2009 [NPWMD] Neuman...] Springthorpe Limited, Manning House, 21 Bucks Road, Douglas IM1 3DA, Man, Isle of; Business Registration...

Tertiary structure in N-linked oligosaccharides.

PubMed

Homans, S W; Dwek, R A; Rademacher, T W

1987-10-06

Distance constraints derived from two-dimensional nuclear Overhauser effect measurements have been used to define the orientation of the Man alpha 1-3Man beta linkage in seven different N-linked oligosaccharides, all containing the common pentasaccharide core Man alpha 1-6(Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc. Conformational invariance of the Man alpha 1-3Man beta linkage was found for those structures bearing substitutions on the Man alpha 1-3Man beta antenna. However, the presence of either a GlcNAc residue in the beta 1-4 linkage to Man beta ("bisecting GlcNAc") or a xylose residue in the beta 1-2 linkage to Man beta of the trimannosyl core was found to generate conformational transitions that were similar. These transitions were accompanied by characteristic chemical shift perturbations of proton resonances in the vicinity of the Man alpha 1-3Man beta linkage. Molecular orbital energy calculations suggest that the conformational transition between the unsubstituted and substituted cores arises from energetic constraints in the vicinity of the Man alpha 1-3Man beta linkage, rather than specific long-range interactions. These data taken together with our previous results on the Man alpha 1-6Man beta linkage [Homans, S. W., Dwek R. A., Boyd, J., Mahmoudian, M., Richards, W. G., & Rademacher, T. W. (1986) Biochemistry 25, 6342] allow us to discuss the consequences of the modulation of oligosaccharide solution conformations.

The Nature of Man and Its Implications.

ERIC Educational Resources Information Center

Pedrini, D. T.; Gregory, Lura N.

The many problems presented by the nature of man and in studying man are the focus of this paper which attempts to place these problems in perspective in terms of the past and future. The enigma facing man, that man must study man, is related in an introduction. Freud's, Adler's, and Jung's developments in the study of the nature of man are…

Mannans and endo-β-mannanases (MAN) in Brachypodium distachyon: expression profiling and possible role of the BdMAN genes during coleorhiza-limited seed germination

PubMed Central

González-Calle, Virginia; Barrero-Sicilia, Cristina; Carbonero, Pilar; Iglesias-Fernández, Raquel

2015-01-01

Immunolocalization of mannans in the seeds of Brachypodium distachyon reveals the presence of these polysaccharides in the root embryo and in the coleorhiza in the early stages of germination (12h), decreasing thereafter to the point of being hardly detected at 27h. Concurrently, the activity of endo-β-mannanases (MANs; EC 3.2.1.78) that catalyse the hydrolysis of β-1,4 bonds in mannan polymers, increases as germination progresses. The MAN gene family is represented by six members in the Brachypodium genome, and their expression has been explored in different organs and especially in germinating seeds. Transcripts of BdMAN2, BdMAN4 and BdMAN6 accumulate in embryos, with a maximum at 24–30h, and are detected in the coleorhiza and in the root by in situ hybridization analyses, before root protrusion (germination sensu stricto). BdMAN4 is not only present in the embryo root and coleorhiza, but is abundant in the de-embryonated (endosperm) imbibed seeds, while BdMAN2 and BdMAN6 are faintly expressed in endosperm during post-germination (36–42h). BdMAN4 and BdMAN6 transcripts are detected in the aleurone layer. These data indicate that BdMAN2, BdMAN4 and BdMAN6 are important for germination sensu stricto and that BdMAN4 and BdMAN6 may also influence reserve mobilization. Whether the coleorhiza in monocots and the micropylar endosperm in eudicots have similar functions, is discussed. PMID:25922488

Policy Implications of a Hierarchy of Values.

ERIC Educational Resources Information Center

Drews, Elizabeth M.

The author examines (in some detail) five images of man--man as a bad animal, man as a blank sheet, man as a mixture of good and evil, man as naturally good, and man as able to transcend himself. Relying on the work of those like Abraham Maslow who follow the view of man as transcendent, the author sets forth her rationale for the assumption that…

NASA Video Catalog. Supplement 15

NASA Technical Reports Server (NTRS)

2005-01-01

This issue of the NASA Video Catalog cites video productions listed in the NASA STI Database. The videos listed have been developed by the NASA centers, covering Shuttle mission press conferences; fly-bys of planets; aircraft design, testing and performance; environmental pollution; lunar and planetary exploration; and many other categories related to manned and unmanned space exploration. Each entry in the publication consists of a standard bibliographic citation accompanied by an abstract. The Table of Contents shows how the entries are arranged by divisions and categories according to the NASA Scope and Coverage Category Guide. For users with specific information, a Title Index is available. A Subject Term Index, based on the NASA Thesaurus, is also included. Guidelines for usage of NASA audio/visual material, ordering information, and order forms are also available.

Recent technology products from Space Human Factors research

NASA Technical Reports Server (NTRS)

Jenkins, James P.

1991-01-01

The goals of the NASA Space Human Factors program and the research carried out concerning human factors are discussed with emphasis given to the development of human performance models, data, and tools. The major products from this program are described, which include the Laser Anthropometric Mapping System; a model of the human body for evaluating the kinematics and dynamics of human motion and strength in microgravity environment; an operational experience data base for verifying and validating the data repository of manned space flights; the Operational Experience Database Taxonomy; and a human-computer interaction laboratory whose products are the display softaware and requirements and the guideline documents and standards for applications on human-computer interaction. Special attention is given to the 'Convoltron', a prototype version of a signal processor for synthesizing the head-related transfer functions.

NASA Video Catalog. Supplement 13

NASA Technical Reports Server (NTRS)

2003-01-01

This issue of the NASA Video Catalog cites video productions listed in the NASA STI Database. The videos listed have been developed by the NASA centers, covering Shuttle mission press conferences; fly-bys of planets; aircraft design, testing and performance; environmental pollution; lunar and planetary exploration; and many other categories related to manned and unmanned space exploration. Each entry in the publication consists of a standard bibliographic citation accompanied by an abstract. The Table of Contents shows how the entries are arranged by divisions and categories according to the NASA Scope and Coverage Category Guide. For users with specific information, a Title Index is available. A Subject Term Index, based on the NASA Thesaurus, is also included. Guidelines for usage of NASA audio/visual material, ordering information, and order forms are also available.

NASA Video Catalog. Supplement 14

NASA Technical Reports Server (NTRS)

2004-01-01

This issue of the NASA Video Catalog cites video productions listed in the NASA STI Database. The videos listed have been developed by the NASA centers, covering Shuttle mission press conferences; fly-bys of planets; aircraft design, testing and performance; environmental pollution; lunar and planetary exploration; and many other categories related to manned and unmanned space exploration. Each entry in the publication consists of a standard bibliographic citation accompanied by an abstract. The Table of Contents shows how the entries are arranged by divisions and categories according to the NASA Scope and Coverage Category Guide. For users with specific information, a Title Index is available. A Subject Term Index, based on the NASA Thesaurus, is also included. Guidelines for usage of NASA audio/visual material, ordering information, and order forms are also available.

NASA Video Catalog

NASA Technical Reports Server (NTRS)

2006-01-01

This issue of the NASA Video Catalog cites video productions listed in the NASA STI database. The videos listed have been developed by the NASA centers, covering Shuttle mission press conferences; fly-bys of planets; aircraft design, testing and performance; environmental pollution; lunar and planetary exploration; and many other categories related to manned and unmanned space exploration. Each entry in the publication consists of a standard bibliographic citation accompanied by an abstract. The Table of Contents shows how the entries are arranged by divisions and categories according to the NASA Scope and Subject Category Guide. For users with specific information, a Title Index is available. A Subject Term Index, based on the NASA Thesaurus, is also included. Guidelines for usage of NASA audio/visual material, ordering information, and order forms are also available.

Intergenerational Transmission of the Behavioral Consequences of Early Experience in Prairie Voles

PubMed Central

Stone, Anita Iyengar; Bales, Karen Lisa

2010-01-01

We examined intergenerational and epigenetic effects of early handling manipulations on the social behavior of the prairie vole (Microtus ochrogaster), a monogamous rodent. Laboratory-born parents and their newborn pups were assigned to either a MAN0 “zero handling” manipulation (transfer with a cup during weekly cage changes) or a MAN1 “gloved handling” manipulation (transfer with a gloved hand). Previous studies from our laboratory (Bales et al. 2007) showed that MAN0 juvenile males that received this manipulation as pups are less alloparental and that MAN0 adult females that received this manipulation as pups display impaired pair-bonding. In the present study, when MAN0 and MAN1 pups reached adulthood, they were mated in three combinations (MAN1 female × MAN1 male; MAN0 female × MAN1 male; MAN1 female and MAN0 male). Once the pairs produced offspring, we examined their parental behavior towards their own pups. The offspring of these pairings (F2 generation) also were tested as juveniles for alloparental behavior. MAN1 females paired with a MAN0 male displayed higher levels of parenting behaviors. In the F2 generation, juvenile offspring with a MAN0 parent were less alloparental than were offspring from other pairs. These results suggest that early experiences can be transmitted intergenerationally. PMID:20457234

46 XX karyotype during male fertility evaluation; case series and literature review.

PubMed

Majzoub, Ahmad; Arafa, Mohamed; Starks, Christopher; Elbardisi, Haitham; Al Said, Sami; Sabanegh, Edmund

2017-01-01

Forty-six XX disorder of sex development is an uncommon medical condition observed at times during the evaluation of a man's fertility. The following is a case series and literature review of phenotypically normal men diagnosed with this karyotype. Our goal is to comprehend the patients' clinical presentation as well as their laboratory results aiming to explore options available for their management. A formal literature review through PubMed and MEDLINE databases was performed using "46 XX man" as a word search. A total of 55 patients, including those conveyed in this article were diagnosed with a 46 XX karyotype during their fertility evaluation. The patients' mean age ± s.d. was 34 ± 10 years and their mean height ± s.d. was 166 ± 6.5 cm. Overall, they presented with hypergonadotropic hypogonadism. Sexual dysfunction, reduced hair distribution, and gynecomastia were reported in 20% (4/20), 25.8% (8/31), and 42% (13/31) of the patients, respectively. The SRY gene was detected in 36 (83.7%) and was absent in the remaining seven (16.3%) patients. We found that a multidisciplinary approach to management is preferred in 46 XX patients. Screening for remnants of the mullerian ducts and for malignant transformation in dysgenetic gonads is imperative. Hypogonadism should be addressed, while fertility options are in vitro fertilization with donor sperm or adoption.

Meta-synthesis about man as a father and caregiver for a hospitalized child

PubMed Central

dos Reis, Susana Maria Garcia; Leite, Ana Carolina Andrade Biaggi; Alvarenga, Willyane de Andrade; Araújo, Jeferson Santos; Zago, Márcia Maria Fontão; Nascimento, Lucila Castanheira

2017-01-01

ABSTRACT Objective: to identify, analyze and synthesize the father’s experience in care for a hospitalized child from results of primary qualitative studies. Method: this is a qualitative meta-synthesis through which 12 articles were analyzed, selected in the Cumulative Index to Nursing and Allied Health Literature databases, Latin American and Caribbean Literature in Health Sciences, Public Medline, Scopus, PsycINFO and Web of Science, published between 1995 and 2015. The methodological steps proposed by Sandelowski and Barroso were used to systematize the review, as well as concepts from the anthropology of masculinities to analyze and discuss the synthesis. Results: the synthesis was presented by means of two themes: 1) paternal dilemmas - what man feels and faces during the hospitalization of the child, highlighting the emotional involvement and change in the family and work relationship, and 2) paternal identities - masculinities readjusted in view of the child’s illness, which reveals identity marks and repressed fatherhood in the hospital environment. Both themes illustrate the challenges and readjustment of parental identity. Final considerations: to get to know the experiences of the father during the hospitalization of the child and the way in which the challenges for the readjustment of roles related to masculinity could broaden the range of nursing and other health professionals, alerting to the importance of including the father as a protagonist or coadjuvant in the care for hospitalized children.

46 CFR 15.525 - Additional manning requirements for tank vessels.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Additional manning requirements for tank vessels. 15.525... MANNING REQUIREMENTS Manning Requirements; Inspected Vessels § 15.525 Additional manning requirements for tank vessels. Parts 31 and 35 of this chapter contain additional manning requirements applicable to...

Modeling Techniques for Shipboard Manning: A Review and Plan for Development

DTIC Science & Technology

1993-02-01

manning levels. Once manning models have been created, experiments can be conducted to show how changes in the manning structure might affect ship safety...these predictions, users of the manning models can evaluate how changes in crew configurations, manning levels, and voyage profiles affect ship safety...mitigate emergency situations would provide crucial information on how changes in manning structure would affect overall ship safety. Like emergency

Epidemiology of male same-sex behaviour and associated sexual health indicators in low- and middle-income countries: 2003-2007 estimates.

PubMed

Cáceres, C F; Konda, K; Segura, E R; Lyerla, R

2008-08-01

To conduct a systematic review of published and unpublished data from research and public health information systems on the prevalence of male-to-male sex in the total male population; as well as among men who have sex with men (MSM), data on prevalence of heterosexual activity and heterosexual unions; prevalence of condom use with male and female partners; and prevalence of HIV infection and other sexually transmitted infections (STIs). Key indicators were defined (a) among men in the general population: prevalence of sex with a man ever and last year; (b) among MSM: prevalence of heterosexual experiences ever and last year; proportion of male-female transgenders; proportion of sex workers; prevalence of HIV and other STIs, condom use in last sexual encounter; consistent condom use with men last year; never used a condom with a man. With help from key informants, study searches were conducted in Pubmed, LILLACS, institutional databases, conference records and other sources. Methodology and quality of information were assessed, and the best data available for 2003-7 were selected. Indicator estimates from each study were used to propose regional estimate ranges. A total of 83 new entries were entered into the database in addition to the previous 561, totalling 644. Of these, 107 showing 2003-7 data were selected. Many new studies came from sub-Saharan Africa, portraying hidden HIV epidemics among MSM. The most frequently reported estimate was HIV infection, with high estimate ranges in most of the regions, except for Middle East and North Africa and Eastern Europe. The next most frequently reported was lifetime frequency of heterosexual sex, showing that roughly 50% of MSM ever had sex with a woman. The small number of newer studies reporting prevalence of "sex with a man in last 12 months" between 2003 and 2007, did not warrant enough new evidence to revise our 2005 size estimates for MSM populations. A considerable number of new studies with estimates of relevance to understanding sexual behaviour and HIV among MSM were identified, with an encouraging amount of new data coming from sub-Saharan Africa. However, limitations in the quality, utility and comparability of available information persist. At least three measures could be promoted for use in surveillance and academic studies: standardised indicators for MSM studies; standardised operational definitions of, and instructions to describe, variables; and standardised research designs and data gathering strategies. A prerequisite for this all is intense advocacy to ensure a social climate in which research into such matters is prioritised, resources are made available as needed and the human rights of MSM are respected.

Epidemiology of male same-sex behaviour and associated sexual health indicators in low- and middle-income countries: 2003–2007 estimates

PubMed Central

Cáceres, C F; Konda, K; Segura, E R; Lyerla, R

2008-01-01

Objectives: To conduct a systematic review of published and unpublished data from research and public health information systems on the prevalence of male-to-male sex in the total male population; as well as among men who have sex with men (MSM), data on prevalence of heterosexual activity and heterosexual unions; prevalence of condom use with male and female partners; and prevalence of HIV infection and other sexually transmitted infections (STIs). Methods: Key indicators were defined (a) among men in the general population: prevalence of sex with a man ever and last year; (b) among MSM: prevalence of heterosexual experiences ever and last year; proportion of male-female transgenders; proportion of sex workers; prevalence of HIV and other STIs, condom use in last sexual encounter; consistent condom use with men last year; never used a condom with a man. With help from key informants, study searches were conducted in Pubmed, LILLACS, institutional databases, conference records and other sources. Methodology and quality of information were assessed, and the best data available for 2003–7 were selected. Indicator estimates from each study were used to propose regional estimate ranges. Results: A total of 83 new entries were entered into the database in addition to the previous 561, totalling 644. Of these, 107 showing 2003–7 data were selected. Many new studies came from sub-Saharan Africa, portraying hidden HIV epidemics among MSM. The most frequently reported estimate was HIV infection, with high estimate ranges in most of the regions, except for Middle East and North Africa and Eastern Europe. The next most frequently reported was lifetime frequency of heterosexual sex, showing that roughly 50% of MSM ever had sex with a woman. The small number of newer studies reporting prevalence of “sex with a man in last 12 months” between 2003 and 2007, did not warrant enough new evidence to revise our 2005 size estimates for MSM populations. Conclusions: A considerable number of new studies with estimates of relevance to understanding sexual behaviour and HIV among MSM were identified, with an encouraging amount of new data coming from sub-Saharan Africa. However, limitations in the quality, utility and comparability of available information persist. At least three measures could be promoted for use in surveillance and academic studies: standardised indicators for MSM studies; standardised operational definitions of, and instructions to describe, variables; and standardised research designs and data gathering strategies. A prerequisite for this all is intense advocacy to ensure a social climate in which research into such matters is prioritised, resources are made available as needed and the human rights of MSM are respected. PMID:18647866

The Implementation of Madrasah-Based Management (MBM) at Man 1 and Man 2 Serang City, Banten, Indonesia--A Comparative Study

ERIC Educational Resources Information Center

Muhajir

2016-01-01

This study aims to reveal how the real condition of management of Madrasah Aliyah Negeri (MAN) or Islamic Senior High School in Serang is, how the understanding of Madrasah-Based Management (MBM) for the people of MAN 2 and MAN 1 Serang is, and how the implementation of MBM in MAN 2 and MAN 1 Serang. This study has a substantial meaning, both…

42 CFR 84.99 - Man tests; testing conditions; general requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Man tests; testing conditions; general requirements...-Contained Breathing Apparatus § 84.99 Man tests; testing conditions; general requirements. (a) The man tests...) All man tests will be conducted by the Institute. (d) The apparatus will be examined before each man...

42 CFR 84.99 - Man tests; testing conditions; general requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Man tests; testing conditions; general requirements...-Contained Breathing Apparatus § 84.99 Man tests; testing conditions; general requirements. (a) The man tests...) All man tests will be conducted by the Institute. (d) The apparatus will be examined before each man...

42 CFR 84.99 - Man tests; testing conditions; general requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Man tests; testing conditions; general requirements...-Contained Breathing Apparatus § 84.99 Man tests; testing conditions; general requirements. (a) The man tests...) All man tests will be conducted by the Institute. (d) The apparatus will be examined before each man...

42 CFR 84.99 - Man tests; testing conditions; general requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Man tests; testing conditions; general requirements...-Contained Breathing Apparatus § 84.99 Man tests; testing conditions; general requirements. (a) The man tests...) All man tests will be conducted by the Institute. (d) The apparatus will be examined before each man...

Technology and the Nature of Man: Biological Considerations. An Occasional Paper on Man/Society/Technology.

ERIC Educational Resources Information Center

Sherwood, Lauralee

This seminar paper explores biological aspects of the man-technology relationship. From man's beginning and continuing into the future, technology is interwoven extensively in the biological fabric of man. Five facets of the biology-technology interaction are examined: (1) technological innovations enabling man to learn about his biological…

Mannans and endo-β-mannanase transcripts are located in different seed compartments during Brassicaceae germination.

PubMed

Carrillo-Barral, Néstor; Matilla, Angel J; Rodríguez-Gacio, María Del Carmen; Iglesias-Fernández, Raquel

2018-03-01

Mannans but not endo-β-mannanases are mainly found in the mucilage layer of two Brassicaceae seeds. Nonetheless, mannanase mobilization from inner to outer seed layers cannot be ruled out. The contribution of endo-β-mannanase (MAN) genes to the germination of the wild-type Sisymbrium officinale and cultivated Brassica rapa (Brassicaceae) species has been explored. In both species, mannans have been localized to the imbibed external seed coat layer (mucilage) by fluorescence immunolocalization and MAN enzymatic activity increases in seeds as imbibition progresses, reaching a peak before 100% germination is achieved. The MAN gene families have been annotated and the expression of their members analyzed in vegetative and reproductive organs. In S. officinale and B. rapa, MAN2, MAN5, MAN6, and MAN7 transcripts accumulate upon seed imbibition. SoMAN7 is the most expressed MAN gene in S. officinale germinating seeds, as occurs with its ortholog in Arabidopsis thaliana, but in B. rapa, the most abundant transcripts are BrMAN2 and BrMAN5. These genes (MAN2, MAN5, MAN6, and MAN7) are localized, by mRNA in situ hybridization, to the micropylar at the endosperm layer and to the radicle in S. officinale, but in B. rapa, these mRNAs are faintly found to the micropylar living seed coat layer and are mainly present at the radicle tip and the vascular bundles. If the domestication process undergone by B. rapa is responsible for these different MAN expression patterns, upon germination remains to be elucidated. Since mannans and MAN genes are not spatially distributed in the same seed tissues, a movement of MAN enzymes that are synthesized with typical signal peptides from the embryo tissues to the mucilage layer (via apoplastic space) is necessary for the mannans to be hydrolyzed.

Elliptic Curve Cryptography with Security System in Wireless Sensor Networks

NASA Astrophysics Data System (ADS)

Huang, Xu; Sharma, Dharmendra

2010-10-01

The rapid progress of wireless communications and embedded micro-electro-system technologies has made wireless sensor networks (WSN) very popular and even become part of our daily life. WSNs design are generally application driven, namely a particular application's requirements will determine how the network behaves. However, the natures of WSN have attracted increasing attention in recent years due to its linear scalability, a small software footprint, low hardware implementation cost, low bandwidth requirement, and high device performance. It is noted that today's software applications are mainly characterized by their component-based structures which are usually heterogeneous and distributed, including the WSNs. But WSNs typically need to configure themselves automatically and support as hoc routing. Agent technology provides a method for handling increasing software complexity and supporting rapid and accurate decision making. This paper based on our previous works [1, 2], three contributions have made, namely (a) fuzzy controller for dynamic slide window size to improve the performance of running ECC (b) first presented a hidden generation point for protection from man-in-the middle attack and (c) we first investigates multi-agent applying for key exchange together. Security systems have been drawing great attentions as cryptographic algorithms have gained popularity due to the natures that make them suitable for use in constrained environment such as mobile sensor information applications, where computing resources and power availability are limited. Elliptic curve cryptography (ECC) is one of high potential candidates for WSNs, which requires less computational power, communication bandwidth, and memory in comparison with other cryptosystem. For saving pre-computing storages recently there is a trend for the sensor networks that the sensor group leaders rather than sensors communicate to the end database, which highlighted the needs to prevent from the man-in-the middle attack. A designed a hidden generator point that offer a good protection from the man-in-the middle (MinM) attack which becomes one of major worries for the sensor's networks with multiagent system is also discussed.

Efficacy of Botulinum toxin A for the treatment of Bladder pain syndrome: A systematic review.

PubMed

Ochoa Vargas, D C; García Perdómo, H A

2018-04-01

To determine the efficacy and safety of BTX-A, compared with other interventions for the treatment of BPS to improve quality of life. This systematic review fulfils all the requirements of the Cochrane manual and PRISMA reporting guidelines. The PROSPERO registration number is: CRD42016039480.Clinical trials without language discrimination were included. BPS patients over 18 y/o that were treated with BTX-A were included. Studies were searched in published databases and no published literature from inception to the present day. Risk of bias analysis was done using the Cochrane risk of bias tool. 88 articles were found with the designed search strategies. After exclusions, four studies were included in the qualitative analyses. Kasyan et al., 2012 compared BTX-A with hydrodistention. Manning et al., 2014 compared the injection of BTX-A with the injection of normal saline in previously hydrodistended bladders. In both cases, primary end point was measured by the O'Leary-Sant questionnaire score. El-Bahnasy et al., 2009 compared BTX-A with BCG administration, through Global Response Assessment. Kuo et al., 2015 compared hydrodistention plus suburothelial injections of BTX-A with hydrodistension plus normal saline injections. Reduction in pain was estimated by VAS bladder pain score. A similar efficacy to their controls had been found in Kasyan and Manning studies. El-Bahnasy had found improvement in BTX-A in all parameters. Kuo el al. 2015, found a significantly reduction in pain in the BTX-A group. Regarding the risk of bias, three studies did not have adequate descriptions of selection, performance and detection bias. The study of Manning had low risk of selection, attrition and reporting bias. There is not enough evidence to conclude the efficacy of BTX-A for the treatment of interstitial cystitis to improve quality of life. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Man-systems integration and the man-machine interface

NASA Technical Reports Server (NTRS)

Hale, Joseph P.

1990-01-01

Viewgraphs on man-systems integration and the man-machine interface are presented. Man-systems integration applies the systems' approach to the integration of the user and the machine to form an effective, symbiotic Man-Machine System (MMS). A MMS is a combination of one or more human beings and one or more physical components that are integrated through the common purpose of achieving some objective. The human operator interacts with the system through the Man-Machine Interface (MMI).

The study of the mechanisms of the different phenotypical manifestations in patients with reciprocal translocations

NASA Astrophysics Data System (ADS)

Lozynskyi, Rostyslav; Lozynska, Maria

2006-04-01

Cytogenetical study of lymphocytes using the light microscopy could reveal a large amount of chromosomal abnormalities, which determine corresponding hereditary disorders. However, geneticists sometimes observe the cases where the same chromosomal rearrangements seen in light microscope cause quite different phenotype (from normal to abnormal) in relatives. The aim of the study was to explain the mechanisms of the different phenotype appearance in family members carrying the same reciprocal translocations. It was carried out the standard chromosome analysis in 12 families, where some relatives had reciprocal translocations. Chromosomes were differentially stained using G-method. The samples were analysed in optical microscope (x1000). Using OMIM gene map, UCSC Genome Browser, eGenome Release v2.3 and Unigene databases it was revealed transposons and transposon derivates in chromosome regions involved in translocations. We suppose that the variability of clinical manifestations in translocation-bearing patient is caused by the influence of the transposons, such as Hsmar2, Alu-elements or some others. We propose the following mechanisms of transposone action in these patients. The first may lie on recombination between the 2 specific DNA-transposon containing sites on different chromosomes resulting in balanced reciprocal translocation with no significant influence on the most genes' activity in corresponding regions. The weakening of transposase repression, which may follow in gametes, increases the transposase activity, and hereby, the probability of transposon dislocation. Dislocation can change the activity of groups of genes, because transposons often carry the regulatory sequences. This can induce multiply innate disorders in the progeny of the phenotypically healthy parents, carrying the translocation. According to the second mechanism, the reciprocal translocation is caused by recombination between 2 Alu repeats. These repeats can undergo reverse transcription, and a DNA-product, formed during this process, can paste in a new chromosome region in gametes. As the Alu repeats contain the CpG-islands, they can change the gene activity resulting in a disorder. The understanding of the cases of such genetical disorders might help to predict the appearance of the progeny with pathological karyotype, making the light microscopy more informative in diagnostic of the diseases.

77 FR 23806 - Manning Rail, Inc.-Acquisition and Operation Exemption-Manning Grain Company

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35607] Manning Rail, Inc.--Acquisition and Operation Exemption--Manning Grain Company Manning Rail, Inc. (MRI), a noncarrier, has filed a verified notice of exemption \\1\\ under 49 CFR 1150.31 to acquire from Manning Grain Company (MGC) and operate a 7.1-mile rail line...

Cloning and expression of a novel UDP-GlcNAc:alpha-D-mannoside beta1,2-N-acetylglucosaminyltransferase homologous to UDP-GlcNAc:alpha-3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I.

PubMed Central

Zhang, Wenli; Betel, Doron; Schachter, Harry

2002-01-01

A TBLASTN search with human UDP-GlcNAc:alpha-3-d-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT I; EC 2.4.1.101) as a probe identified human and mouse Unigenes encoding a protein similar to human GnT I (34% identity over 340 amino acids). The recombinant protein converted Man(alpha1-6)[Man(alpha1-3)]Man(beta1-)O-octyl to Man(alpha1-6)[GlcNAc(beta1-2)Man(alpha1-3)]Man(beta1-)O-octyl, the reaction catalysed by GnT I. The enzyme also added GlcNAc to Man(alpha1-6)[GlcNAc(beta1-2)Man(alpha1-3)]Man(beta1-)O-octyl (the substrate for beta-1,2-N-acetylglucosaminyltransferase II), Man(alpha1-)O-benzyl [with K(m) values of approximately 0.3 and >30 mM for UDP-GlcNAc and Man(alpha1-)O-benzyl respectively] and the glycopeptide CYA[Man(alpha1-)O-T]AV (K(m) approximately 12 mM). The product formed with Man(alpha1-)O-benzyl was identified as GlcNAc(beta1-2)Man(alpha1-)O-benzyl by proton NMR spectroscopy. The enzyme was named UDP-GlcNAc:alpha-d-mannoside beta-1,2-N-acetylglucosaminyltransferase I.2 (GnT I.2). The human gene mapped to chromosome 1. Northern-blot analysis showed a 3.3 kb message with a wide tissue distribution. The cDNA has a 1980 bp open reading frame encoding a 660 amino acid protein with a type-2 domain structure typical of glycosyltransferases. Man(beta1-)O-octyl, Man(beta1-)O-p-nitrophenyl and GlcNAc(beta1-2)Man(alpha1-6)[GlcNAc(beta1-2)Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc(beta1-)O-Asn were not acceptors, indicating that GnT I.2 is specific for alpha-linked terminal Man and does not have N-acetylglucosaminyltransferase III, IV, V, VII or VIII activities. CYA[Man(alpha1-)O-T]AV was between three and seven times more effective as an acceptor than the other substrates, suggesting that GnT I.2 may be responsible for the synthesis of the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety on alpha-dystroglycan and other O-mannosylated proteins. PMID:11742540

Data management with a landslide inventory of the Franconian Alb (Germany) using a spatial database and GIS tools

NASA Astrophysics Data System (ADS)

Bemm, Stefan; Sandmeier, Christine; Wilde, Martina; Jaeger, Daniel; Schwindt, Daniel; Terhorst, Birgit

2014-05-01

The area of the Swabian-Franconian cuesta landscape (Southern Germany) is highly prone to landslides. This was apparent in the late spring of 2013, when numerous landslides occurred as a consequence of heavy and long-lasting rainfalls. The specific climatic situation caused numerous damages with serious impact on settlements and infrastructure. Knowledge on spatial distribution of landslides, processes and characteristics are important to evaluate the potential risk that can occur from mass movements in those areas. In the frame of two projects about 400 landslides were mapped and detailed data sets were compiled during years 2011 to 2014 at the Franconian Alb. The studies are related to the project "Slope stability and hazard zones in the northern Bavarian cuesta" (DFG, German Research Foundation) as well as to the LfU (The Bavarian Environment Agency) within the project "Georisks and climate change - hazard indication map Jura". The central goal of the present study is to create a spatial database for landslides. The database should contain all fundamental parameters to characterize the mass movements and should provide the potential for secure data storage and data management, as well as statistical evaluations. The spatial database was created with PostgreSQL, an object-relational database management system and PostGIS, a spatial database extender for PostgreSQL, which provides the possibility to store spatial and geographic objects and to connect to several GIS applications, like GRASS GIS, SAGA GIS, QGIS and GDAL, a geospatial library (Obe et al. 2011). Database access for querying, importing, and exporting spatial and non-spatial data is ensured by using GUI or non-GUI connections. The database allows the use of procedural languages for writing advanced functions in the R, Python or Perl programming languages. It is possible to work directly with the (spatial) data entirety of the database in R. The inventory of the database includes (amongst others), informations on location, landslide types and causes, geomorphological positions, geometries, hazards and damages, as well as assessments related to the activity of landslides. Furthermore, there are stored spatial objects, which represent the components of a landslide, in particular the scarps and the accumulation areas. Besides, waterways, map sheets, contour lines, detailed infrastructure data, digital elevation models, aspect and slope data are included. Examples of spatial queries to the database are intersections of raster and vector data for calculating values for slope gradients or aspects of landslide areas and for creating multiple, overlaying sections for the comparison of slopes, as well as distances to the infrastructure or to the next receiving drainage. Furthermore, getting informations on landslide magnitudes, distribution and clustering, as well as potential correlations concerning geomorphological or geological conditions. The data management concept in this study can be implemented for any academic, public or private use, because it is independent from any obligatory licenses. The created spatial database offers a platform for interdisciplinary research and socio-economic questions, as well as for landslide susceptibility and hazard indication mapping. Obe, R.O., Hsu, L.S. 2011. PostGIS in action. - pp 492, Manning Publications, Stamford

High Voltage EEE Parts for EMA/EHA Applications on Manned Launch Vehicles

NASA Technical Reports Server (NTRS)

Griffin, Trent; Young, David

2011-01-01

The objective of this paper is an assessment of high voltage electronic components required for high horsepower electric thrust vector control (TVC) systems for human spaceflight launch critical application. The scope consists of creating of a database of available Grade 1 electrical, electronic and electromechanical (EEE) parts suited to this application, a qualification path for potential non-Grade 1 EEE parts that could be used in these designs, and pathfinder testing to validate aspects of the proposed qualification plan. Advances in the state of the art in high power electric power systems enable high horsepower electric actuators, such as the electromechnical actuator (EMA) and the electro-hydrostatic actuator (EHA), to be used in launch vehicle TVC systems, dramaticly reducing weight, complexity and operating costs. Designs typically use high voltage insulated gate bipolar transistors (HV-IGBT). However, no Grade 1 HV-IGBT exists and it is unlikely that market factors alone will produce such high quality parts. Furthermore, the perception of risk, the lack of qualification methodoloy, the absence of manned space flight heritage and other barriers impede the adoption of commercial grade parts onto the critical path. The method of approach is to identify high voltage electronic component types and key parameters for parts currently used in high horsepower EMA/EHA applications, to search for higher quality substitutes and custom manufacturers, to create a database for these parts, and then to explore ways to qualify these parts for use in human spaceflight launch critical application, including grossly derating and possibly treating hybrid parts as modules. This effort is ongoing, but results thus far include identification of over 60 HV-IGBT from four manufacturers, including some with a high reliability process flow. Voltage ranges for HV-IGBT have been identified, as has screening tests used to characterize HV-IGBT. BSI BS ISO 21350 Space systems Off-the-shelf item utilization, developed from Marshall Work Instruction MWI8060.1 OFF-THE-SHELF HARDWARE UTILIZATION IN FLIGHT HARDWARE DEVELOPMENTwas found to provide guidance for including commercial off-the-shelf (COTS) hardware for use in critical applications.

Comparison of Efficacy Between Endoscopic Cyclophotocoagulation and Alternative Surgeries in Refractory Glaucoma

PubMed Central

Yang, Yangfan; Zhong, Jing; Dun, Zhongjun; Liu, Xiao-an; Yu, Minbin

2015-01-01

Abstract Refractory glaucoma refers to uncontrolled intraocular pressure (IOP) despite anti-glaucoma medication and surgical treatment, which remains a challenge to be treated. The objective of this study is to evaluate and statistically compare the clinical efficacy between endoscopic cyclophotocoagulation (ECP) and alternative surgical techniques in the treatment of refractory glaucoma in this article, as a meta-analysis. Data sources are China Biomedical Database (Sinomed, online version), China National Knowledge Infrastructure (CNKI), Cqvip, Wanfang database, and PubMed. The randomized controlled trial (RCT) and case–control study literatures evaluating the clinical efficacy between ECP and other surgical techniques were searched electronically from public databases. The methodology quality of the retrieved articles was evaluated according to the RCT or case–control study criteria. The success rate of treatment, intraocular pressure (IOP) and visual acuity were statistically compared. RevMan 5.3 software was used for the meta-analysis. In total, 6 relevant control studies were selected in this study with a total sampling of 429 cases (429 eyes), including 204 eyes in the ECP group and 225 in the non-ECP group. Meta-analysis demonstrated that the clinical efficacy did not significantly differ between 2 groups (P > 0.05). Postoperative IOP was dramatically reduced in both groups. However, it was difficult to evaluate the combined influence of ECP and non-ECP therapies upon IOP reduction. In conclusion, ECP and non-ECP treatment yielded almost equivalent clinical efficacy in treating refractory glaucoma. The IOP-lowering degree, safety, and incidence of complications remain to be further elucidated by RCTs with a larger sample size. PMID:26426659

Can Ashi points stimulation have specific effects on shoulder pain? A systematic review of randomized controlled trials.

PubMed

Wang, Kang-Feng; Zhang, Li-Juan; Lu, Feng; Lu, Yong-Hui; Yang, Chuan-Hua

2016-06-01

To provide an evidence-based overview regarding the efficacy of Ashi points stimulation for the treatment of shoulder pain. A comprehensive search [PubMed, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), Chongqing Weipu Database for Chinese Technical Periodicals (VIP) and Wanfang Database] was conducted to identify randomized or quasi-randomized controlled trials that evaluated the effectiveness of Ashi points stimulation for shoulder pain compared with conventional treatment. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. RevMan 5.0 was used for data synthesis. Nine trials were included. Seven studies assessed the effectiveness of Ashi points stimulation on response rate compared with conventional acupuncture. Their results suggested significant effect in favour of Ashi points stimulation [odds ratio (OR): 5.89, 95% confidence interval (CI): 2.97 to 11.67, P<0.01, heterogeneity: χ(2) =3.81, P=0.70, I (2) =0% ]. One trial compared Ashi points stimulation with drug therapy. The result showed there was a significantly greater recovery rate in group of Ashi points stimulation (OR: 9.58, 95% CI: 2.69 to 34.12). One trial compared comprehensive treatment on the myofascial trigger points (MTrPs) with no treatment and the result was in favor of MTrPs. Ashi points stimulation might be superior to conventional acupuncture, drug therapy and no treatment for shoulder pain. However, due to the low methodological quality of included studies, a firm conclusion could not be reached until further studies of high quality are available.

Glycoprotein synthesis in yeast. Identification of Man8GlcNAc2 as an essential intermediate in oligosaccharide processing.

PubMed

Byrd, J C; Tarentino, A L; Maley, F; Atkinson, P H; Trimble, R B

1982-12-25

Synthesis of the N-linked oligosaccharides of Saccharomyces cerevisiae glycoproteins has been studied in vivo by labeling with [2-3H]mannose and gel filtration analysis of the products released by endoglycosidase H. Both small oligosaccharides, Man8-14GlcNAc, and larger products, Man greater than 20GlcNAc, were labeled. The kinetics of continuous and pulse-chase labeling demonstrated that Glc3Man9GlcNAc2, the initial product transferred to protein, was rapidly (t1/2 congruent to 3 min) trimmed to Man8GlcNAc2 and then more slowly (t1/2 = 10-20 min) elongated to larger oligosaccharides. No oligosaccharides smaller than Man8GlcNAc2 were evident with either labeling procedure. In confirmation of the trimming reaction observed in vivo, 3H-labeled Man9-N-acetylglucosaminitol from bovine thyroglobulin and [14C]Man9GlcNAc2 from yeast oligosaccharide-lipid were converted in vitro by broken yeast cells to 3H-labeled Man8-N-acetylglucosaminitol and [14C]Man8GlcNAc2. Man8GlcNAc and Man9GlcNAc from yeast invertase and from bovine thyroglobulin were purified by gel filtration and examined by high field 1H-NMR analysis. Invertase Man8GlcNAc (B) and Man9GlcNAc (C) were homogeneous compounds, which differed from the Man9GlcNAc (A) of thyroglobulin by the absence of a specific terminal alpha 1,2-linked mannose residue. The Man9GlcNAc of invertase (C) had an additional terminal alpha 1,6-linked mannose and appeared identical in structure with that isolated from yeast containing the mnn1 and mnn2 mutations (Cohen, R. E., Zhang, W.-j., and Ballou, C. E. (1982) J. Biol. Chem. 257, 5730-5737). It is concluded that Man8GlcNAc2, formed by removal of glucose and a single mannose from Glc3Man9GlcNAc2, is the ultimate product of trimming and the minimal precursor for elongation of the oligosaccharides on yeast glycoproteins. The results suggest that removal of a particular terminal alpha 1,2-linked mannose from Man9GlcNAc2 by a highly specific alpha-mannosidase exposes the nascent Man-alpha 1,6-Man backbone for elongation with additional alpha 1,6-linked mannose residues, according to the following scheme: (formula, see text).

The rights of man and animal experimentation.

PubMed Central

Martin, J

1990-01-01

Since emotions give contradictory signals about animal experimentation in medical science, man's relationship to animals must be based upon reason. Thomas Aquinas argues that man is essentially different from animals because man's intellectual processes show evidence of an abstract mechanism not possessed by animals. Man's rights arise in association with this essential difference. The consequence is that only man possesses true rights by Aquinas's definition; animals have them only by analogy. However, cruelty to animals is illicit and they should be protected, principally not because they have rights, but because he who is cruel to animals is more likely to be cruel to his fellowman. If there is a need for animal experimentation in science for the good of man, this approach gives philosophical justification for experimentation, since man's well-being must come before that of animals because of his unique possession of rights. However, those experiments should be carried out in the kindest way possible, to promote kindness towards man. To see man as solely part of a biological continuum in competition for rights with those beings close to him biologically, detracts from man's dignity. PMID:2135948

EMU Lessons Learned Database

NASA Technical Reports Server (NTRS)

Matthews, Kevin M., Jr.; Crocker, Lori; Cupples, J. Scott

2011-01-01

As manned space exploration takes on the task of traveling beyond low Earth orbit, many problems arise that must be solved in order to make the journey possible. One major task is protecting humans from the harsh space environment. The current method of protecting astronauts during Extravehicular Activity (EVA) is through use of the specially designed Extravehicular Mobility Unit (EMU). As more rigorous EVA conditions need to be endured at new destinations, the suit will need to be tailored and improved in order to accommodate the astronaut. The Objective behind the EMU Lessons Learned Database(LLD) is to be able to create a tool which will assist in the development of next-generation EMUs, along with maintenance and improvement of the current EMU, by compiling data from Failure Investigation and Analysis Reports (FIARs) which have information on past suit failures. FIARs use a system of codes that give more information on the aspects of the failure, but if one is unfamiliar with the EMU they will be unable to decipher the information. A goal of the EMU LLD is to not only compile the information, but to present it in a user-friendly, organized, searchable database accessible to all familiarity levels with the EMU; both newcomers and veterans alike. The EMU LLD originally started as an Excel database, which allowed easy navigation and analysis of the data through pivot charts. Creating an entry requires access to the Problem Reporting And Corrective Action database (PRACA), which contains the original FIAR data for all hardware. FIAR data are then transferred to, defined, and formatted in the LLD. Work is being done to create a web-based version of the LLD in order to increase accessibility to all of Johnson Space Center (JSC), which includes converting entries from Excel to the HTML format. FIARs related to the EMU have been completed in the Excel version, and now focus has shifted to expanding FIAR data in the LLD to include EVA tools and support hardware such as the Pistol Grip Tool (PGT) and the Battery Charger Module (BCM), while adding any recently closed EMU-related FIARs.

Traditional Chinese and western medicine for the prevention of deep venous thrombosis after lower extremity orthopedic surgery: a meta-analysis of randomized controlled trials.

PubMed

Zhu, Shibai; Song, Yi; Chen, Xi; Qian, Wenwei

2018-04-10

Chinese herbal medicine has traditionally been considered to promote blood circulation to remove obstruction in the channels and clear pathogenic heat to drain dampness effects. We conducted this meta-analysis to evaluate its benefits for the prevention of deep venous thrombosis (DVT) after lower extremity orthopedic surgery. Relevant, published studies were identified using the following keywords: lower extremity orthopedic surgery, arthroplasty, joint replacement, fracture, traditional Chinese and western medicine, Chinese herbal medicine, deep venous thrombosis (DVT), and Venous thromboembolism (VTE). The following databases were used to identify the literature consisting of RCTs with a date of search of 31 May 2017: PubMed, Cochrane Library, Web of knowledge, the Chinese National Knowledge Infrastructure Database, the Chongqing VIP Database, the Chinese Biomedical Database, and the Wanfang Database (including three English and four Chinese databases). All relevant data were collected from studies meeting the inclusion criteria. The outcome variables were the incidence rate of DVT, activated partial thromboplastin time (APTT), prothrombin time (PT), and D-dimer; subcutaneous hematoma; and other reported outcomes. RevMan5.2. software was adopted for the meta-analysis. A total of 20 published studies (1862 cases) met the inclusion criteria. The experimental group, 910 patients (48.87%), received the Chinese herbal medicine or traditional Chinese and western medicine for prevention of DVT; the control group, 952 patients (51.13%), received the standard western treatment. The meta-analysis showed that traditional Chinese and western medicine therapy reduced the incidence rates of DVT significantly when compared with controls (risk ratio [RR] = 0.40; 95% CI, 0.30 to 0.54; P < 0.00001), and the D-dimer was lower in the experimental group (P = 0.01). Besides, the incidence rate of subcutaneous hematoma was lower in the experimental group (P < 0.0001). However, no significant difference was found in the PT (P = 0.98) and APTT (P = 0.75) in two groups. No serious adverse events were reported. Traditional Chinese and western medicine therapy may be a safe, effective prevention modality for DVT after lower extremity orthopedic surgery. Further rigorously designed, randomized trials are warranted.

The Isolation of DNA by Polycharged Magnetic Particles: An Analysis of the Interaction by Zeta Potential and Particle Size

PubMed Central

Haddad, Yazan; Xhaxhiu, Kledi; Kopel, Pavel; Hynek, David; Zitka, Ondrej; Adam, Vojtech

2016-01-01

Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158 (phosphate-coated), and MAN164 (tripolyphosphate-coated). All particles were positive polycharged agglomerated monodispersed systems. Mean particle sizes were 0.48, 2.97, 2.93, and 3.67 μm for MAN37, MAN127, MAN164, and MAN158, respectively. DNA fragments exhibited negative zeta potential of −0.22 mV under binding conditions (high ionic strength, low pH, and dehydration). A decrease in zeta potential of particles upon exposure to DNA was observed with exception of MAN158 particles. The measured particle size of MAN164 particles increased by nearly twofold upon exposure to DNA. Quantitative PCR isolation of DNA with a high retrieval rate was observed by magnetic particles MAN127 and MAN164. Interaction between polycharged magnetic particles and DNA is mediated by various binding mechanisms such as hydrophobic and electrostatic interactions. Future development of DNA isolation technology requires an understanding of the physical and biochemical conditions of this process. PMID:27104527

The Isolation of DNA by Polycharged Magnetic Particles: An Analysis of the Interaction by Zeta Potential and Particle Size.

PubMed

Haddad, Yazan; Xhaxhiu, Kledi; Kopel, Pavel; Hynek, David; Zitka, Ondrej; Adam, Vojtech

2016-04-20

Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158 (phosphate-coated), and MAN164 (tripolyphosphate-coated). All particles were positive polycharged agglomerated monodispersed systems. Mean particle sizes were 0.48, 2.97, 2.93, and 3.67 μm for MAN37, MAN127, MAN164, and MAN158, respectively. DNA fragments exhibited negative zeta potential of -0.22 mV under binding conditions (high ionic strength, low pH, and dehydration). A decrease in zeta potential of particles upon exposure to DNA was observed with exception of MAN158 particles. The measured particle size of MAN164 particles increased by nearly twofold upon exposure to DNA. Quantitative PCR isolation of DNA with a high retrieval rate was observed by magnetic particles MAN127 and MAN164. Interaction between polycharged magnetic particles and DNA is mediated by various binding mechanisms such as hydrophobic and electrostatic interactions. Future development of DNA isolation technology requires an understanding of the physical and biochemical conditions of this process.

Insect midgut α-mannosidases from family 38 and 47 with emphasis on those of Tenebrio molitor.

PubMed

Moreira, Nathalia R; Cardoso, Christiane; Ribeiro, Alberto F; Ferreira, Clelia; Terra, Walter R

2015-12-01

α-Mannosidases are enzymes which remove non-reducing terminal residues from glycoconjugates. Data on both GH47 and GH38 (Golgi and lysosomal) enzymes are available. Data on insect midgut α-mannosidases acting in digestion are preliminary and do not include enzyme sequences. Tenebrio molitor midgut α-mannosidases were separated by chromatography into two activity peaks: a major (Man1) and a minor (Man2). An antibody generated against a synthetic peptide corresponding to a sequence of α-mannosidase fragment recognizes Man2 but not Man1. That fragment was later found to correspond to TmMan2 (GenBank access KP892646), showing that the cDNA coding for Man2 is actually TmMan2. TmMan2 codes for a mature α-mannosidase with 107.5 kDa. Purified Man2 originates after SDS-PAGE one band of about 72 kDa and another of 51 kDa, which sums 123 kDa, in agreement with gel filtration (123 kDa) data. These results suggest that Man2 is processed into peptides that remain noncovalently linked within the functional enzyme. The physical and kinetical properties of purified Man1 and Man2 are similar. They have a molecular mass of 123 kDa (gel filtration), pH optimum (5.6) and response to inhibitors like swainsonine (Man1 Ki, 68 nM; Man2 Ki, 63 nM) and deoxymannojirimycin (Man1 Ki, 0.12 mM; Man2 Ki, 0.15 mM). Their substrate specificities are a little different as Man2 hydrolyzes α-1,3 and α-1,6 bonds better than α-1,2, whereas the contrary is true for Man1. Thus, they pertain to Class II (GH38 α-mannosidases), that are catabolic α-mannosidases similar to lysosomal α-mannosidase. However, Man2, in contrast to true lysosomal α-mannosidase, is secreted (immunocytolocalization data) into the midgut contents. There, Man2 may participate in digestion of fungal cell walls, known to have α-mannosides in their outermost layer. The amount of family 38 α-mannosidase sequences found in the transcriptome (454 pyrosequencing) of the midgut of 9 insects pertaining to 5 orders is perhaps related to the diet of these organisms, as suggested by a large number of lysosomal α-mannosidase in the T. molitor midgut. Copyright © 2015 Elsevier Ltd. All rights reserved.

Occupational Accidents with Agricultural Machinery in Austria.

PubMed

Kogler, Robert; Quendler, Elisabeth; Boxberger, Josef

2016-01-01

The number of recognized accidents with fatalities during agricultural and forestry work, despite better technology and coordinated prevention and trainings, is still very high in Austria. The accident scenarios in which people are injured are very different on farms. The common causes of accidents in agriculture and forestry are the loss of control of machine, means of transport or handling equipment, hand-held tool, and object or animal, followed by slipping, stumbling and falling, breakage, bursting, splitting, slipping, fall, and collapse of material agent. In the literature, a number of studies of general (machine- and animal-related accidents) and specific (machine-related accidents) agricultural and forestry accident situations can be found that refer to different databases. From the database Data of the Austrian Workers Compensation Board (AUVA) about occupational accidents with different agricultural machinery over the period 2008-2010 in Austria, main characteristics of the accident, the victim, and the employer as well as variables on causes and circumstances by frequency and contexts of parameters were statistically analyzed by employing the chi-square test and odds ratio. The aim of the study was to determine the information content and quality of the European Statistics on Accidents at Work (ESAW) variables to evaluate safety gaps and risks as well as the accidental man-machine interaction.

Common variants in Mendelian kidney disease genes and their association with renal function.

PubMed

Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

2013-12-01

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

Do psychological interventions reduce depression in hemodialysis patients?: A meta-analysis of randomized controlled trials following PRISMA.

PubMed

Xing, Lu; Chen, Ruiqi; Diao, Yongshu; Qian, Jiahui; You, Chao; Jiang, Xiaolian

2016-08-01

Depression is highly prevalent in hemodialysis patients and results in poor patient outcomes. Although psychological interventions are being developed and used for these patients, there is uncertainty regarding the effectiveness of these interventions. The purpose of this meta-analysis is to evaluate the effects of psychological interventions on depression treatment in hemodialysis patients. All randomized controlled trials (RCTs) relevant to the depression treatment of hemodialysis patients through psychological interventions were retrieved from the following databases: Embase, Pubmed, PsycINFO, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. The reference lists of identified RCTs were also screened. The Cochrane risk of bias tool was used to evaluate the quality of the studies, RevMan (5.3) was used to analyze the data, and the evidence quality of the combined results was evaluated using GRADE (3.6.1). Eight RCTs were included. The combined results showed that psychological interventions significantly reduced the scores of the Beck Depression Inventory (P<0.001) and interdialysis weight gain (P<0.001). However, due to the high heterogeneity, effect size combinations of sleep quality and quality of life were not performed. Psychological interventions may reduce the degree of depression and improve fluid intake restriction adherence. More rigorously designed research is needed.

Reconstruction of a Functional Human Gene Network, with an Application for Prioritizing Positional Candidate Genes

PubMed Central

Franke, Lude; Bakel, Harm van; Fokkens, Like; de Jong, Edwin D.; Egmont-Petersen, Michael; Wijmenga, Cisca

2006-01-01

Most common genetic disorders have a complex inheritance and may result from variants in many genes, each contributing only weak effects to the disease. Pinpointing these disease genes within the myriad of susceptibility loci identified in linkage studies is difficult because these loci may contain hundreds of genes. However, in any disorder, most of the disease genes will be involved in only a few different molecular pathways. If we know something about the relationships between the genes, we can assess whether some genes (which may reside in different loci) functionally interact with each other, indicating a joint basis for the disease etiology. There are various repositories of information on pathway relationships. To consolidate this information, we developed a functional human gene network that integrates information on genes and the functional relationships between genes, based on data from the Kyoto Encyclopedia of Genes and Genomes, the Biomolecular Interaction Network Database, Reactome, the Human Protein Reference Database, the Gene Ontology database, predicted protein-protein interactions, human yeast two-hybrid interactions, and microarray coexpressions. We applied this network to interrelate positional candidate genes from different disease loci and then tested 96 heritable disorders for which the Online Mendelian Inheritance in Man database reported at least three disease genes. Artificial susceptibility loci, each containing 100 genes, were constructed around each disease gene, and we used the network to rank these genes on the basis of their functional interactions. By following up the top five genes per artificial locus, we were able to detect at least one known disease gene in 54% of the loci studied, representing a 2.8-fold increase over random selection. This suggests that our method can significantly reduce the cost and effort of pinpointing true disease genes in analyses of disorders for which numerous loci have been reported but for which most of the genes are unknown. PMID:16685651

Molecular differences between mature and immature dental pulp cells: Bioinformatics and preliminary results.

PubMed

Chen, Long; Jiang, Yifeng; Du, Zhen

2018-04-01

Although previous studies have demonstrated that dental pulp stem cells (DPSCs) from mature and immature teeth exhibit potential for multi-directional differentiation, the molecular and biological difference between the DPSCs from mature and immature permanent teeth has not been fully investigated. In the present study, 500 differentially expressed genes from dental pulp cells (DPCs) in mature and immature permanent teeth were obtained from the Gene Expression Omnibus online database. Based on bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery, these genes were divided into a number of subgroups associated with immunity, inflammation and cell signaling. The results of the present study suggest that immune features, response to infection and cell signaling may be different in DPCs from mature and immature permanent teeth; furthermore, DPCs from immature permanent teeth may be more suitable for use in tissue engineering or stem cell therapy. The Online Mendelian Inheritance in Man database stated that Sonic Hedgehog (SHH), a differentially expressed gene in DPCs from mature and immature permanent teeth, serves a crucial role in the development of craniofacial tissues, including teeth, which further confirmed that SHH may cause DPCs from mature and immature permanent teeth to exhibit different biological characteristics. The Search Tool for the Retrieval of Interacting Genes/Proteins database revealed that SHH has functional protein associations with a number of other proteins, including Glioma-associated oncogene (GLI)1, GLI2, growth arrest-specific protein 1, bone morphogenetic protein (BMP)2 and BMP4, in mice and humans. It was also demonstrated that SHH may interact with other genes to regulate the biological characteristics of DPCs. The results of the present study may provide a useful reference basis for selecting suitable DPSCs and molecules for the treatment of these cells to optimize features for tissue engineering or stem cell therapy. Quantitative polymerase chain reaction should be performed to confirm the differential expression of these genes prior to the beginning of a functional study.

Creating a standardized watersheds database for the Lower Rio Grande/Río Bravo, Texas

USGS Publications Warehouse

Brown, J.R.; Ulery, Randy L.; Parcher, Jean W.

2000-01-01

This report describes the creation of a large-scale watershed database for the lower Rio Grande/Río Bravo Basin in Texas. The watershed database includes watersheds delineated to all 1:24,000-scale mapped stream confluences and other hydrologically significant points, selected watershed characteristics, and hydrologic derivative datasets.Computer technology allows generation of preliminary watershed boundaries in a fraction of the time needed for manual methods. This automated process reduces development time and results in quality improvements in watershed boundaries and characteristics. These data can then be compiled in a permanent database, eliminating the time-consuming step of data creation at the beginning of a project and providing a stable base dataset that can give users greater confidence when further subdividing watersheds.A standardized dataset of watershed characteristics is a valuable contribution to the understanding and management of natural resources. Vertical integration of the input datasets used to automatically generate watershed boundaries is crucial to the success of such an effort. The optimum situation would be to use the digital orthophoto quadrangles as the source of all the input datasets. While the hydrographic data from the digital line graphs can be revised to match the digital orthophoto quadrangles, hypsography data cannot be revised to match the digital orthophoto quadrangles. Revised hydrography from the digital orthophoto quadrangle should be used to create an updated digital elevation model that incorporates the stream channels as revised from the digital orthophoto quadrangle. Computer-generated, standardized watersheds that are vertically integrated with existing digital line graph hydrographic data will continue to be difficult to create until revisions can be made to existing source datasets. Until such time, manual editing will be necessary to make adjustments for man-made features and changes in the natural landscape that are not reflected in the digital elevation model data.

Creating a standardized watersheds database for the lower Rio Grande/Rio Bravo, Texas

USGS Publications Warehouse

Brown, Julie R.; Ulery, Randy L.; Parcher, Jean W.

2000-01-01

This report describes the creation of a large-scale watershed database for the lower Rio Grande/Rio Bravo Basin in Texas. The watershed database includes watersheds delineated to all 1:24,000-scale mapped stream confluences and other hydrologically significant points, selected watershed characteristics, and hydrologic derivative datasets. Computer technology allows generation of preliminary watershed boundaries in a fraction of the time needed for manual methods. This automated process reduces development time and results in quality improvements in watershed boundaries and characteristics. These data can then be compiled in a permanent database, eliminating the time-consuming step of data creation at the beginning of a project and providing a stable base dataset that can give users greater confidence when further subdividing watersheds. A standardized dataset of watershed characteristics is a valuable contribution to the understanding and management of natural resources. Vertical integration of the input datasets used to automatically generate watershed boundaries is crucial to the success of such an effort. The optimum situation would be to use the digital orthophoto quadrangles as the source of all the input datasets. While the hydrographic data from the digital line graphs can be revised to match the digital orthophoto quadrangles, hypsography data cannot be revised to match the digital orthophoto quadrangles. Revised hydrography from the digital orthophoto quadrangle should be used to create an updated digital elevation model that incorporates the stream channels as revised from the digital orthophoto quadrangle. Computer-generated, standardized watersheds that are vertically integrated with existing digital line graph hydrographic data will continue to be difficult to create until revisions can be made to existing source datasets. Until such time, manual editing will be necessary to make adjustments for man-made features and changes in the natural landscape that are not reflected in the digital elevation model data.

Visualising biological data: a semantic approach to tool and database integration.

PubMed

Pettifer, Steve; Thorne, David; McDermott, Philip; Marsh, James; Villéger, Alice; Kell, Douglas B; Attwood, Teresa K

2009-06-16

In the biological sciences, the need to analyse vast amounts of information has become commonplace. Such large-scale analyses often involve drawing together data from a variety of different databases, held remotely on the internet or locally on in-house servers. Supporting these tasks are ad hoc collections of data-manipulation tools, scripting languages and visualisation software, which are often combined in arcane ways to create cumbersome systems that have been customized for a particular purpose, and are consequently not readily adaptable to other uses. For many day-to-day bioinformatics tasks, the sizes of current databases, and the scale of the analyses necessary, now demand increasing levels of automation; nevertheless, the unique experience and intuition of human researchers is still required to interpret the end results in any meaningful biological way. Putting humans in the loop requires tools to support real-time interaction with these vast and complex data-sets. Numerous tools do exist for this purpose, but many do not have optimal interfaces, most are effectively isolated from other tools and databases owing to incompatible data formats, and many have limited real-time performance when applied to realistically large data-sets: much of the user's cognitive capacity is therefore focused on controlling the software and manipulating esoteric file formats rather than on performing the research. To confront these issues, harnessing expertise in human-computer interaction (HCI), high-performance rendering and distributed systems, and guided by bioinformaticians and end-user biologists, we are building reusable software components that, together, create a toolkit that is both architecturally sound from a computing point of view, and addresses both user and developer requirements. Key to the system's usability is its direct exploitation of semantics, which, crucially, gives individual components knowledge of their own functionality and allows them to interoperate seamlessly, removing many of the existing barriers and bottlenecks from standard bioinformatics tasks. The toolkit, named Utopia, is freely available from http://utopia.cs.man.ac.uk/.

Synthesis and applications of MANs/poly(MMA-co-BA) nanocomposite latex by miniemulsion polymerization

PubMed Central

Chen, Huayao; Zhou, Xinhua; Gunasekaran, Sundaram

2017-01-01

We have synthesized core-shell structured 3-methacryloxypropyltrimethoxysilane (MPS) functionalized antimony-doped tin oxide nanoparticles (MANs)–poly(methyl methacrylate-co-butyl acrylate) (PMMA-co-BA, PMB) nanocomposite latex particles via miniemulsion polymerization method. Polymerizable anionic surfactant DNS-86 (allyloxy polyoxyethylene(10) nonyl ammonium sulfate) was first introduced to synthesize core-shell nanocomposite. The morphologies of synthesized MANs and MANs/PMB latex nanocomposite particles were studied with transmission electron microscopy, which revealed particles, on average 70 nm in size, with a core-shell structure. Owing to the uniformity and hydrophobicity of MANs, the MANs-embedded PMB latex nanocomposite can be tailored more precisely than other nanoparticles-embedded nanocomposites. Films incorporating 10 wt% of MANs in the MAN/PMB latex nanocomposite exhibit good transmittance in the visible region, and excellent opacity in the near infrared region. The MANs/PMB nanocomposite film also appears suitable for heat insulation applications. PMID:29291076

Leveraging Terminological Resources for Mapping between Rare Disease Information Sources

PubMed Central

Rance, Bastien; Snyder, Michelle; Lewis, Janine; Bodenreider, Olivier

2015-01-01

Background Rare disease information sources are incompletely and inconsistently cross-referenced to one another, making it difficult for information seekers to navigate across them. The development of such cross-references established manually by experts is generally labor intensive and costly. Objectives To develop an automatic mapping between two of the major rare diseases information sources, GARD and Orphanet, by leveraging terminological resources, especially the UMLS. Methods We map the rare disease terms from Orphanet and ORDR to the UMLS. We use the UMLS as a pivot to bridge between the rare disease terminologies. We compare our results to a mapping obtained through manually established cross-references to OMIM. Results Our mapping has a precision of 94%, a recall of 63% and an F1-score of 76%. Our automatic mapping should help facilitate the development of more complete and consistent cross-references between GARD and Orphanet, and is applicable to other rare disease information sources as well. PMID:23920611

Molecular pathogenesis of Spondylocheirodysplastic Ehlers-Danlos syndrome caused by mutant ZIP13 proteins

PubMed Central

Bin, Bum-Ho; Hojyo, Shintaro; Hosaka, Toshiaki; Bhin, Jinhyuk; Kano, Hiroki; Miyai, Tomohiro; Ikeda, Mariko; Kimura-Someya, Tomomi; Shirouzu, Mikako; Cho, Eun-Gyung; Fukue, Kazuhisa; Kambe, Taiho; Ohashi, Wakana; Kim, Kyu-Han; Seo, Juyeon; Choi, Dong-Hwa; Nam, Yeon-Ju; Hwang, Daehee; Fukunaka, Ayako; Fujitani, Yoshio; Yokoyama, Shigeyuki; Superti-Furga, Andrea; Ikegawa, Shiro; Lee, Tae Ryong; Fukada, Toshiyuki

2014-01-01

The zinc transporter protein ZIP13 plays critical roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). Here, we report the molecular pathogenic mechanism of SCD-EDS caused by two different mutant ZIP13 proteins found in human patients: ZIP13G64D, in which Gly at amino acid position 64 is replaced by Asp, and ZIP13ΔFLA, which contains a deletion of Phe-Leu-Ala. We demonstrated that both the ZIP13G64D and ZIP13ΔFLA protein levels are decreased by degradation via the valosin-containing protein (VCP)-linked ubiquitin proteasome pathway. The inhibition of degradation pathways rescued the protein expression levels, resulting in improved intracellular Zn homeostasis. Our findings uncover the pathogenic mechanisms elicited by mutant ZIP13 proteins. Further elucidation of these degradation processes may lead to novel therapeutic targets for SCD-EDS. PMID:25007800

Whole-exome analysis of foetal autopsy tissue reveals a frameshift mutation in OBSL1, consistent with a diagnosis of 3-M Syndrome.

PubMed

Marshall, Christian R; Farrell, Sandra A; Cushing, Donna; Paton, Tara; Stockley, Tracy L; Stavropoulos, Dimitri J; Ray, Peter N; Szego, Michael; Lau, Lynette; Pereira, Sergio L; Cohn, Ronald D; Wintle, Richard F; Abuzenadah, Adel M; Abu-Elmagd, Muhammad; Scherer, Stephen W

2015-01-01

We report a consanguineous couple that has experienced three consecutive pregnancy losses following the foetal ultrasound finding of short limbs. Post-termination examination revealed no skeletal dysplasia, but some subtle proximal limb shortening in two foetuses, and a spectrum of mildly dysmorphic features. Karyotype was normal in all three foetuses (46, XX) and comparative genomic hybridization microarray analysis detected no pathogenic copy number variants. Whole-exome sequencing and genome-wide homozygosity mapping revealed a previously reported frameshift mutation in the OBSL1 gene (c.1273insA p.T425nfsX40), consistent with a diagnosis of 3-M Syndrome 2 (OMIM #612921), which had not been anticipated from the clinical findings. Our study provides novel insight into the early clinical manifestations of this form of 3-M syndrome, and demonstrates the utility of whole exome sequencing as a tool for prenatal diagnosis in particular when there is a family history suggestive of a recurrent set of clinical symptoms.

Benign familial fleck retina: multimodal imaging including optical coherence tomography angiography.

PubMed

Garcia, Jose Mauricio Botto de Barros; Isaac, David Leonardo Cruvinel; Sardeiro, Tainara; Aquino, Érika; Avila, Marcos

2017-01-01

This report presents multimodal imaging of a 27-year-old woman diagnosed with benign familial fleck retina (OMIM 228980), an uncommon disorder. Fundus photographs revealed retinal flecks that affected her post-equatorial retina but spared the macular area. Fundus autofluorescence and infrared imaging demonstrated a symmetrical pattern of yellow-white fleck lesions that affected both eyes. Her full-field electroretinogram and electrooculogram were normal. An optical coherence tomography B-scan was performed for both eyes, revealing increased thickness of the retinal pigmented epithelium leading to multiple small pigmented epithelium detachments. The outer retina remained intact in both eyes. Spectral-domain optical coherence tomography angiography with split-spectrum amplitude decorrelation algorithm and 3 × 3 mm structural en face optical coherence tomography did not show macular lesions. Benign familial fleck retina belongs to a heterogenous group of so-called flecked retina syndromes, and should be considered in patients with yellowish-white retinal lesions without involvement of the macula.

Pulmonary hypoplasia-diaphragmatic hernia-anophthalmia-cardiac defect (PDAC) syndrome due to STRA6 mutations--what are the minimal criteria?

PubMed

Segel, Reeval; Levy-Lahad, Ephrat; Pasutto, Francesca; Picard, Elie; Rauch, Anita; Alterescu, Gheona; Schimmel, Michael S

2009-11-01

Microphthalmic syndrome 9 (OMIM601186) is a genetically and phenotypically variable condition, comprising anophthalmia, pulmonary hypoplasia, diaphragmatic hernia, and cardiac malformations (PDAC syndrome). Reported cases have all been associated with fetal/neonatal death or developmental delay. Recessive stimulated by retinoic acid gene 6 homolog (STRA6) mutations have recently been identified as the cause of cases of PDAC in which distinct, "bushy" eyebrows have been observed. We describe a patient with clinical anophthalmia, bushy eyebrows, patent ductus arteriosus, and normal development at age 30 months, who is a compound heterozygote for two novel STRA6 missense mutations. This patient's phenotype is consistent with the multisystemic malformations of PDAC syndrome, but is somewhat milder. This is the first living patient with compound heterozygous STRA6 mutations, which may explain her milder phenotype. We conclude that STRA6 analysis should be considered in all patients with clinical anophthalmia. Genetic counseling should be cautious with respect to long-term developmental outcomes. Copyright 2009 Wiley-Liss, Inc.

Considering Valproate as a Risk Factor for Rapid Exacerbation of Complex Movement Disorder in Progressed Stages of Late-Infantile CLN2 Disease.

PubMed

Johannsen, Jessika; Nickel, Miriam; Schulz, Angela; Denecke, Jonas

2016-06-01

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease, OMIM 204500) is a rare autosomal-recessive lysosomal storage disorder. It is one of the most common neurodegenerative disorders in childhood. Symptoms include epilepsy, rapid motor and language regression, dementia, visual loss, and a complex movement disorder in later stages of the disease. We report on two children with genetically confirmed late-infantile CLN2 disease who developed a severe exacerbation of their complex movement disorder leading to hyperthermia, hyper-CK-emia and decreased level of consciousness over several weeks despite different therapeutic approaches. Both patients were on long-term antiepileptic treatment with valproate and only after the withdrawal of valproate, the movement disorder disappeared and level of consciousness improved. These observations emphasize that valproate has to be considered as a possible risk factor in patients in later stages of late-infantile CLN2 disease who develop a rapidly progressive complex movement disorder. Georg Thieme Verlag KG Stuttgart · New York.

The Unified Medical Language System (UMLS): integrating biomedical terminology

PubMed Central

Bodenreider, Olivier

2004-01-01

The Unified Medical Language System (http://umlsks.nlm.nih.gov) is a repository of biomedical vocabularies developed by the US National Library of Medicine. The UMLS integrates over 2 million names for some 900 000 concepts from more than 60 families of biomedical vocabularies, as well as 12 million relations among these concepts. Vocabularies integrated in the UMLS Metathesaurus include the NCBI taxonomy, Gene Ontology, the Medical Subject Headings (MeSH), OMIM and the Digital Anatomist Symbolic Knowledge Base. UMLS concepts are not only inter-related, but may also be linked to external resources such as GenBank. In addition to data, the UMLS includes tools for customizing the Metathesaurus (MetamorphoSys), for generating lexical variants of concept names (lvg) and for extracting UMLS concepts from text (MetaMap). The UMLS knowledge sources are updated quarterly. All vocabularies are available at no fee for research purposes within an institution, but UMLS users are required to sign a license agreement. The UMLS knowledge sources are distributed on CD-ROM and by FTP. PMID:14681409

Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus

PubMed Central

Graham, Deborah S Cunninghame; Pinder, Christopher L; Tombleson, Philip; Behrens, Timothy W; Martín, Javier; Fairfax, Benjamin P; Knight, Julian C; Chen, Lingyan; Replogle, Joseph; Syvänen, Ann-Christine; Rönnblom, Lars; Graham, Robert R; Wither, Joan E; Rioux, John D; Alarcón-Riquelme, Marta E; Vyse, Timothy J

2015-01-01

Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry: a new GWAS, meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including 10 novel associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n=16) of transcription factors among SLE susceptibility genes. This supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE. PMID:26502338

Ionic liquid [OMIm][OAc] directly inducing oxidation cleavage of the β-O-4 bond of lignin model compounds.

PubMed

Yang, Yingying; Fan, Honglei; Meng, Qinglei; Zhang, Zhaofu; Yang, Guanying; Han, Buxing

2017-08-03

We explored the oxidation reactions of lignin model compounds directly induced by ionic liquids under metal-free conditions. In this work, it was found that ionic liquid 1-octyl-3-methylimidazolium acetate as a solvent could promote the aerobic oxidation of lignin model compound 2-phenoxyacetophenone (1) and the yields of phenol and benzoic acid from 1 could be as high as 96% and 86%, respectively. A possible reaction pathway was proposed based on a series of control experiments. An acetate anion from the ionic liquid attacked the hydrogen from the β-carbon thereby inducing the cleavage of the C-O bond of the aromatic ether. Furthermore, it was found that 2-(2-methoxyphenoxy)-1-phenylethanone (4) with a methoxyl group could also be transformed into aromatic products in this simple reaction system and the yields of phenol and benzoic acid from 4 could be as high as 98% and 85%, respectively. This work provides a simple way for efficient transformation of lignin model compounds.

Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration

PubMed Central

Wan, Jijun; Yourshaw, Michael; Mamsa, Hafsa; Rudnik-Schöneborn, Sabine; Menezes, Manoj P.; Hong, Ji Eun; Leong, Derek W.; Senderek, Jan; Salman, Michael S.; Chitayat, David; Seeman, Pavel; von Moers, Arpad; Graul-Neumann, Luitgard; Kornberg, Andrew J.; Castro-Gago, Manuel; Sobrido, María-Jesús; Sanefuji, Masafumi; Shieh, Perry B.; Salamon, Noriko; Kim, Ronald C.; Vinters, Harry V.; Chen, Zugen; Zerres, Klaus; Ryan, Monique M.; Nelson, Stanley F.; Jen, Joanna C.

2012-01-01

RNA exosomes are multi-subunit complexes conserved throughout evolution1 and emerging as the major cellular machinery for processing, surveillance, and turnover of a diverse spectrum of coding and non-coding RNA substrates essential for viability2. By exome sequencing, we discovered recessive mutations in exosome component 3 (EXOSC3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly, and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 [PCH1; OMIM 607596]3–6. We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment with small brain and poor motility, reminiscent of human clinical features and largely rescued by coinjected wildtype but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome gene responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration. PMID:22544365

Identification of IFRD1 variant in a Han Chinese family with autosomal dominant hereditary spastic paraplegia associated with peripheral neuropathy and ataxia.

PubMed

Lin, Pengfei; Zhang, Dong; Xu, Guangrun; Yan, Chuanzhu

2018-04-01

Spinocerebellar ataxias (SCAs) are a group of autosomal dominant, clinically heterogeneous neurodegenerative disorders. SCA18 is a rare autosomal dominant sensory/motor neuropathy with ataxia (OMIM#607458) associated with a single missense variant c.514 A>G in the interferon related developmental regulator 1 (IFRD1) gene previously reported in a five-generation American family of Irish origin. However, to date, there have been no other reports of the IFRD1 mutation to confirm its role in SCA. Here, we report a Han Chinese family with SCA18; the family members presented with a slowly progressing gait ataxia, pyramidal tract signs, and peripheral neuropathy. We identified a missense variant (c.514 A>G, p.I172V) in IFRD1 gene in the family using targeted next-generation sequencing and Sanger direct sequencing with specific primers. Our results suggest that the IFRD1 gene may be the causative allele for SCA18.

Chimerism for 20q11.2 microdeletion of GDF5 explains discordant phenotypes in monochorionic-diamniotic twins.

PubMed

Meredith, Matthew M; Crabb, Beau; Vargas, Marcelo; Hirsch, Betsy A

2017-12-01

Microdeletions of 20q11.2 are rare but have been associated with characteristic clinical findings. A 1.6 Mb minimal critical region has been identified that includes three OMIM genes: GDF5, EPB41L1, and SAMHD. Here we describe a male monozygotic, monochorionic-diamniotic twin pair with discordant phenotypes, one with multiple findings that overlap with those reported in 20q11.2 deletions, and the other unaffected. Microarray analysis revealed mosaicism for a 363 Kb deletion encompassing GDF5 in the peripheral blood of both twins, which was confirmed by FISH. Subsequent FISH on buccal cells identified the deletion only in the affected twin. The blood FISH findings were interpreted as representing chimerism resulting from anastomosis and the blood exchange between the twins in utero. The implications of this finding are discussed, as is the contribution of GDF5 to the associated clinical findings of 20q11.2 deletions. © 2017 Wiley Periodicals, Inc.

Syndromic intellectual disability: a new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant.

PubMed

Graziano, Claudio; Wischmeijer, Anita; Pippucci, Tommaso; Fusco, Carlo; Diquigiovanni, Chiara; Nõukas, Margit; Sauk, Martin; Kurg, Ants; Rivieri, Francesca; Blau, Nenad; Hoffmann, Georg F; Chaubey, Alka; Schwartz, Charles E; Romeo, Giovanni; Bonora, Elena; Garavelli, Livia; Seri, Marco

2015-04-01

The causative variant in a consanguineous family in which the three patients (two siblings and a cousin) presented with intellectual disability, Marfanoid habitus, craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has been identified through whole exome sequencing (WES) analysis. WES study identified a homozygous DDC variant in the patients, c.1123C>T, resulting in p.Arg375Cys missense substitution. Mutations in DDC cause a recessive metabolic disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643) characterized by hypotonia, oculogyric crises, excessive sweating, temperature instability, dystonia, severe neurologic dysfunction in infancy, and specific abnormalities of neurotransmitters and their metabolites in the cerebrospinal fluid (CSF). In our family, analysis of neurotransmitters and their metabolites in patient's CSF shows a pattern compatible with AADC deficiency, although the clinical signs are different from the classic form. Our work expands the phenotypic spectrum associated with DDC variants, which therefore can cause an additional novel syndrome without typical movement abnormalities. Copyright © 2015 Elsevier B.V. All rights reserved.

Urea Cycle Defects: Early-Onset Disease Associated with A208T Mutation in OTC Gene-Expanding the Clinical Phenotype.

PubMed

Sánchez, Ana Isabel; Rincón, Alejandra; García, Mary; Suárez-Obando, Fernando

2017-01-01

Ornithine transcarbamylase deficiency (OMIM: 311250) is the most common disorder of urea cycle disorders, accounting for nearly 50% of all cases. We report a case of a two-month- old male patient, who attends our medical genetics consultation because of low citrulline levels and elevated glutamine to citrulline ratio detected by expanded newborn screening with tandem mass spectrometry. He is an asymptomatic male with a normal physical examination and appropriate neurodevelopmental milestones. The patient has a family history of one older brother who died at 18 months old from severe and sudden hyperammonemia and a maternal aunt who suddenly died at two years old. He had high plasma ammonium concentration and a confirmed OTC mutation (p.A208T). Usually, this mutation causes OTC deficiency of late onset in adult males. However, this report raises awareness about mutations previously described as a late-onset causing disease, which can cause severe hyperammonemia and high risk of dying at an early age.

A novel splicing mutation in GALT gene causing Galactosemia in Ecuadorian family.

PubMed

De Lucca, M; Barba, C; Casique, L

2017-07-01

Classic Galactosemia (OMIM 230400) is an autosomal recessive disorder of galactose metabolism caused by mutations in the galactose-1-phosphate uridyl transferase (GALT) gene. This disease caused by the inability to metabolize galactose is potentially life-threatening but its pathophysiology has not been clearly defined. GALT gene presents high allelic heterogeneity and around 336 variations have been identified. Here, we report the case of a patient with Classic Galactosemia who was detected during a neonatal screening in Ecuador. Molecular study revealed a mutation in GALT gene intron 1, c.82+3A>G in homozygous condition, this mutation has not been previously reported. This gene variation was not found in any of the 119 healthy Ecuadorian individuals used as control. Furthermore, the mutation was the only alteration detected in the propositus's GALT after sequencing all exons and introns of this gene. In silico modeling predicted that the mutation was pathogenic. Copyright © 2017. Published by Elsevier B.V.

Increased frequency of rhabdomyolysis in familial dysautonomia.

PubMed

Palma, Jose-Alberto; Roda, Ricardo; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

2015-11-01

Familial dysautonomia (FD; OMIM # 223900) is an autosomal recessive disease with features of impaired pain and temperature perception and lack of functional muscle spindles. After 3 FD patients presented with rhabdomyolysis in a short time span, we aimed to determine the frequency of rhabdomyolysis is this population. This study was a retrospective chart review of 665 FD patients. Eight patients had at least 1 episode of rhabdomyolysis. Two patients had 2 episodes. The average incidence of rhabdomyolysis in FD was 7.5 per 10,000 person-years. By comparison, the average incidence with statins has been reported to be 0.44 per 10,000 person-years. Mean maximum creatine kinase (CK) level was 32,714 ± 64,749 U/L. Three patients had hip magnetic resonance imaging showing gluteal hyperintensities. Patients with FD have an increased incidence of rhabdomyolysis. We hypothesize that this may result from a combination of absent functional muscle spindles and muscle mitochondrial abnormalities. © 2015 Wiley Periodicals, Inc.

The Unified Medical Language System (UMLS): integrating biomedical terminology.

PubMed

Bodenreider, Olivier

2004-01-01

The Unified Medical Language System (http://umlsks.nlm.nih.gov) is a repository of biomedical vocabularies developed by the US National Library of Medicine. The UMLS integrates over 2 million names for some 900,000 concepts from more than 60 families of biomedical vocabularies, as well as 12 million relations among these concepts. Vocabularies integrated in the UMLS Metathesaurus include the NCBI taxonomy, Gene Ontology, the Medical Subject Headings (MeSH), OMIM and the Digital Anatomist Symbolic Knowledge Base. UMLS concepts are not only inter-related, but may also be linked to external resources such as GenBank. In addition to data, the UMLS includes tools for customizing the Metathesaurus (MetamorphoSys), for generating lexical variants of concept names (lvg) and for extracting UMLS concepts from text (MetaMap). The UMLS knowledge sources are updated quarterly. All vocabularies are available at no fee for research purposes within an institution, but UMLS users are required to sign a license agreement. The UMLS knowledge sources are distributed on CD-ROM and by FTP.

LIDAR vs. GEODAS land elevation data in hurricane induced inundation modelling

NASA Astrophysics Data System (ADS)

Peng, M.; Pietrafesa, L. J.; Bao, S.; Liu, H.; Xia, M.; Yan, T.

2007-04-01

LIDAR (Light Detection and Ranging) and GEODAS (GEOphysical DAta System) are respectively taken as the land elevation data for a 3-D storm surge and inundation model to investigate the subsequent inundation differences. Hilton Head, South Carolina, and Croatan-Albemarle-Pamlico Estuary System (CAPES), North Carolina, are the two investigated regions. Significant inundation differences with LIDAR versus GEODAS are found in both regions. The modeled inundation area with GEODAS is larger than with LIDAR. For Category 2-3 hypothetical hurricanes, the maximum inundation difference in Hilton Head region is 67%, while the difference in the CAPES is 156%. Generally, vertical precision difference of the two databases is the major reason for the inundation difference. Recently constructed man-made structures, not included in the GEODAS, but included in the LIDAR data sets may be another contributing reason.

Behavioral activation in the treatment of metacognitive dysfunctions in inhibited-type personality disorders.

PubMed

Gordon-King, Keely; Schweitzer, Robert D; Dimaggio, Giancarlo

2017-09-01

Behavioral interventions are proposed as a critical treatment component in psychotherapy for personality disorders. The current study explores behavioral interventions as a mechanism of change in Metacognitive Interpersonal Therapy, an integrative psychotherapy for personality disorders. The goals and implementation of behavioral principles are illustrated through the single case study of Roger, a 57-year-old man diagnosed with avoidant personality disorder and depressive personality disorder. Transcripts of interviews and therapy sessions illustrate the role of behavioral interventions, including behavioral activation, in Roger's treatment. Roger demonstrated a reliable change from baseline to posttreatment across all measures. He also showed gains with regard to his occupational functioning, interpersonal relationships, and sense of fulfilment. Implications with regard to treatment planning for personality disorders are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

GAGES: A stream gage database for evaluating natural and alteredflow conditions in the conterminous United States

USGS Publications Warehouse

Falcone, James A.; Carlisle, Daren M.; Wolock, David M.; Meador, Michael R.

2010-01-01

In addition, watersheds were assessed for their reference quality within nine broad regions for use in studies intended to characterize stream flows under conditions minimally influenced by human activities. Three primary criteria were used to assess reference quality: (1) a quantitative index of anthropogenic modification within the watershed based on GIS-derived variables, (2) visual inspection of every stream gage and drainage basin from recent high-resolution imagery and topographic maps, and (3) information about man-made influences from USGS Annual Water Data Reports. From the set of 6785 sites, we identified 1512 as reference-quality stream gages. All data derived for these watersheds as well as the reference condition evaluation are provided as an online data set termed GAGES (geospatial attributes of gages for evaluating stream flow).

The place of psychodynamic psychotherapy in the integrated treatment of posttraumatic stress disorder and trauma recovery.

PubMed

Moss, Eric

2009-06-01

Psychodynamic psychotherapists treating posttraumatic stress disorder (PTSD) sufferers can draw on an accumulated body of trauma studies from their own field to guide their work. However, these reports, often based on case studies or conceptual reviews, do not have the same empirical conclusiveness as more recent evidence-based research demonstrating the efficacy of cognitive-behavioral and body-oriented therapies. In this article, a psychodynamic psychotherapist reflects on his treatment of an Israeli man who developed PTSD after enduring 4 terrorist attacks. The author shows how assimilative integration offered him a theory- and research-based model that helped him comfortably combine separate treatment interventions. He also shows how this model helped him locate with some precision the specific contribution of psychodynamic psychotherapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

A PC-Based Free Text DSS for Health Care

NASA Technical Reports Server (NTRS)

Grams, Ralph R.; Buchanan, Paul; Massey, James K.; Jin, Ming

1987-01-01

A free Decision Support System(DST) has been constructed for health care professional that allows the analysis of complex medical cases and the creation of diagnostic list of potential diseases for clinical evaluation.The system uses a PC-based text management system specifically designed for desktop operation. The texts employed in the decision support package include the Merck Manual (published by Merck Sharpe & Dohme) and Control of Communicable Diseas in Man (published by the American Public Health Association). The background and design of the database are discussed along with a structured analysis procedure for handling free text DSS system. A case study is presented to show the application of this technology and conclusions are drawn in the summary that point to expanded areas of professional intention and new frontiers yet to be explored in this rapidly progressing field.

Unified Access Architecture for Large-Scale Scientific Datasets

NASA Astrophysics Data System (ADS)

Karna, Risav

2014-05-01

Data-intensive sciences have to deploy diverse large scale database technologies for data analytics as scientists have now been dealing with much larger volume than ever before. While array databases have bridged many gaps between the needs of data-intensive research fields and DBMS technologies (Zhang 2011), invocation of other big data tools accompanying these databases is still manual and separate the database management's interface. We identify this as an architectural challenge that will increasingly complicate the user's work flow owing to the growing number of useful but isolated and niche database tools. Such use of data analysis tools in effect leaves the burden on the user's end to synchronize the results from other data manipulation analysis tools with the database management system. To this end, we propose a unified access interface for using big data tools within large scale scientific array database using the database queries themselves to embed foreign routines belonging to the big data tools. Such an invocation of foreign data manipulation routines inside a query into a database can be made possible through a user-defined function (UDF). UDFs that allow such levels of freedom as to call modules from another language and interface back and forth between the query body and the side-loaded functions would be needed for this purpose. For the purpose of this research we attempt coupling of four widely used tools Hadoop (hadoop1), Matlab (matlab1), R (r1) and ScaLAPACK (scalapack1) with UDF feature of rasdaman (Baumann 98), an array-based data manager, for investigating this concept. The native array data model used by an array-based data manager provides compact data storage and high performance operations on ordered data such as spatial data, temporal data, and matrix-based data for linear algebra operations (scidbusr1). Performances issues arising due to coupling of tools with different paradigms, niche functionalities, separate processes and output data formats have been anticipated and considered during the design of the unified architecture. The research focuses on the feasibility of the designed coupling mechanism and the evaluation of the efficiency and benefits of our proposed unified access architecture. Zhang 2011: Zhang, Ying and Kersten, Martin and Ivanova, Milena and Nes, Niels, SciQL: Bridging the Gap Between Science and Relational DBMS, Proceedings of the 15th Symposium on International Database Engineering Applications, 2011. Baumann 98: Baumann, P., Dehmel, A., Furtado, P., Ritsch, R., Widmann, N., "The Multidimensional Database System RasDaMan", SIGMOD 1998, Proceedings ACM SIGMOD International Conference on Management of Data, June 2-4, 1998, Seattle, Washington, 1998. hadoop1: hadoop.apache.org, "Hadoop", http://hadoop.apache.org/, [Online; accessed 12-Jan-2014]. scalapack1: netlib.org/scalapack, "ScaLAPACK", http://www.netlib.org/scalapack,[Online; accessed 12-Jan-2014]. r1: r-project.org, "R", http://www.r-project.org/,[Online; accessed 12-Jan-2014]. matlab1: mathworks.com, "Matlab Documentation", http://www.mathworks.de/de/help/matlab/,[Online; accessed 12-Jan-2014]. scidbusr1: scidb.org, "SciDB User's Guide", http://scidb.org/HTMLmanual/13.6/scidb_ug,[Online; accessed 01-Dec-2013].

Identification of the antigenic determinants of factors 8, 9, and 34 of genus Candida.

PubMed

Kobayashi, H; Oyamada, H; Suzuki, A; Shibata, N; Suzuki, S; Okawa, Y

1996-10-21

We investigated the antigenic determinants of factors 8, 9, and 34 of the genus Candida among pathogenic yeasts by enzyme-linked immunosorbent assay (ELISA) using mannans of Saccharomyces cerevisiae wild type and mutant types, mnn 1-mnn 4 and mnn 2. Results of ELISA including antisera against the antigenic factors of genus Candida (Candida Check, latron; FAbs) indicated that these three types of mannan distinctly react with FAbs 34, 8 and 9, respectively. To identify the recognition sites of these FAbs, we compared the ability of various oligosaccharides to inhibit the binding of the mannans to FAbs. The results indicated that FAb 34 preferentially recognizes linear side chains containing a non-reducing terminal alpha-1,3-linked mannose residue, Man(alpha)1 --> 3Man(alpha)1 --> (2Man(alpha)1 --> )n(2Man) (n > or = 0), and that one of the recognition sites of FAb 9 is linear alpha-1,6-linked oligomannosyl series, Man(alpha)1 --> (6Man(alpha)1 --> )n(6Man) (n > or = 2). On the other hand, the recognition site of FAb 8 apparently consisted of two alpha-1,2-linked oligomannosyl side chains and an alpha-1,6-linked mannose residue that originated from the mannan backbone, Man(alpha)1 --> 2Man(alpha)1 --> 2(Man(alpha)1 -->2Man(alpha)1 --> 6)Man.

75 FR 81715 - Additional Designation of Entities Pursuant to Executive Order 13382

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... follows: Entities: 1. ASHTEAD SHIPPING COMPANY LIMITED, Manning House, 21 Bucks Road, Douglas IM1 3DA, Man... Square, Pasdaran Avenue, PO Box 19395-1311, Tehran, Iran; Business Registration Document 108116C (Man...: 982120100486 [NPWMD] 2. BYFLEET SHIPPING COMPANY LIMITED, Manning House, 21 Bucks Road, Douglas IM1 3DA, Man...

Psychological Model of a Person Dedicated to His Profession

ERIC Educational Resources Information Center

Sadovaya, Victoriya V.; Korchagina, Galina I.

2016-01-01

The heterogeneity of the social structure of modern society changes the image of a "working man." Well-established images prevailing in the XX century (an economic man, a functional man, a psychological man) are replaced by a new image--"a self-organizing man." This construct describes a "smart" class. According to…

46 CFR 151.45-3 - Manning.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Manning. 151.45-3 Section 151.45-3 Shipping COAST GUARD... HAZARDOUS MATERIAL CARGOES Operations § 151.45-3 Manning. Except as provided for in this section, barges need not be manned unless in the judgment of the Officer in Charge, Marine Inspection, such manning is...

46 CFR 151.45-3 - Manning.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Manning. 151.45-3 Section 151.45-3 Shipping COAST GUARD... HAZARDOUS MATERIAL CARGOES Operations § 151.45-3 Manning. Except as provided for in this section, barges need not be manned unless in the judgment of the Officer in Charge, Marine Inspection, such manning is...

46 CFR 151.45-3 - Manning.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Manning. 151.45-3 Section 151.45-3 Shipping COAST GUARD... HAZARDOUS MATERIAL CARGOES Operations § 151.45-3 Manning. Except as provided for in this section, barges need not be manned unless in the judgment of the Officer in Charge, Marine Inspection, such manning is...

46 CFR 151.45-3 - Manning.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Manning. 151.45-3 Section 151.45-3 Shipping COAST GUARD... HAZARDOUS MATERIAL CARGOES Operations § 151.45-3 Manning. Except as provided for in this section, barges need not be manned unless in the judgment of the Officer in Charge, Marine Inspection, such manning is...

The Black Man in American Society.

ERIC Educational Resources Information Center

Framingham Public Schools, MA.

GRADE OR AGES: Junior high school. SUBJECT MATTER: The black man in American society. ORGANIZATION AND PHYSICAL APPEARANCE: There are four major parts each with an overview. The four parts concern a) the African heritage of the black man, b) the American exploitation of the black man, c) the black man's contribution to American society, d) the…

Roles and needs of man in space

NASA Technical Reports Server (NTRS)

Von Puttkamer, J.

1983-01-01

Human capabilities and requirements on space missions are discussed. Utilitarian and humanistic motivations for manned missions are considered, and a general program of development from easy space access and return, to a permanent LEO presence, to the limited self-sufficiency of man in space, is proposed. Man's potential as scientific observer, operator, and engineer/technician is illustrated with examples from the Apollo and Skylab missions. It is shown that future increases in man's space presence will require significant improvements in habitation technology, crew comfort and safety, operational effectiveness and reliability, and man/machine interactions: man-tended systems must be standardized and adapted to (mainly EVA) human servicing; permanently manned systems must be designed to attain levels of comfort, privacy, and overall habitability more like those expected on the ground.

Comparative analyses of two thermophilic enzymes exhibiting both beta-1,4 mannosidic and beta-1,4 glucosidic cleavage activities from Caldanaerobius polysaccharolyticus.

PubMed

Han, Yejun; Dodd, Dylan; Hespen, Charles W; Ohene-Adjei, Samuel; Schroeder, Charles M; Mackie, Roderick I; Cann, Isaac K O

2010-08-01

The hydrolysis of polysaccharides containing mannan requires endo-1,4-beta-mannanase and 1,4-beta-mannosidase activities. In the current report, the biochemical properties of two endo-beta-1,4-mannanases (Man5A and Man5B) from Caldanaerobius polysaccharolyticus were studied. Man5A is composed of an N-terminal signal peptide (SP), a catalytic domain, two carbohydrate-binding modules (CBMs), and three surface layer homology (SLH) repeats, whereas Man5B lacks the SP, CBMs, and SLH repeats. To gain insights into how the two glycoside hydrolase family 5 (GH5) enzymes may aid the bacterium in energy acquisition and also the potential application of the two enzymes in the biofuel industry, two derivatives of Man5A (Man5A-TM1 [TM1 stands for truncational mutant 1], which lacks the SP and SLH repeats, and Man5A-TM2, which lacks the SP, CBMs, and SLH repeats) and the wild-type Man5B were biochemically analyzed. The Man5A derivatives displayed endo-1,4-beta-mannanase and endo-1,4-beta-glucanase activities and hydrolyzed oligosaccharides with a degree of polymerization (DP) of 4 or higher. Man5B exhibited endo-1,4-beta-mannanase activity and little endo-1,4-beta-glucanase activity; however, this enzyme also exhibited 1,4-beta-mannosidase and cellodextrinase activities. Man5A-TM1, compared to either Man5A-TM2 or Man5B, had higher catalytic activity with soluble and insoluble polysaccharides, indicating that the CBMs enhance catalysis of Man5A. Furthermore, Man5A-TM1 acted synergistically with Man5B in the hydrolysis of beta-mannan and carboxymethyl cellulose. The versatility of the two enzymes, therefore, makes them a resource for depolymerization of mannan-containing polysaccharides in the biofuel industry. Furthermore, on the basis of the biochemical and genomic data, a molecular mechanism for utilization of mannan-containing nutrients by C. polysaccharolyticus is proposed.

Experiences in Being.

ERIC Educational Resources Information Center

Marshall, Bernice, Ed.

A set of essays are subsumed under four broad headings: man as man, man with himself, man with others, and man and his institutions. The essays are personal and concern the authors' feelings in response to himself, others, or the institutions he is part of. Each essay is followed by a discussion about it. The book is described as an application of…

A Technological Determinist Viewpoint of the Stanton-Staggers Conflict over "The Selling of the Pentagon": Print Man Versus Electronic Man.

ERIC Educational Resources Information Center

Breen, Myles P.

Media, specifically documentary films on television, profoundly affect both social structure and man's psychological percepts. The clash of views depicted is between "print man" (using U.S. Representative Harley Staggers as an example) and "electronic man" (portrayed as Frank Stanton of CBS) centering on Stagger's objections to…

Development of real-time PCR assay for genetic identification of the mottled skate, Beringraja pulchra.

PubMed

Hwang, In Kwan; Lee, Hae Young; Kim, Min-Hee; Jo, Hyun-Su; Choi, Dong-Ho; Kang, Pil-Won; Lee, Yang-Han; Cho, Nam-Soo; Park, Ki-Won; Chae, Ho Zoon

2015-10-01

The mottled skate, Beringraja pulchra is one of the commercially important fishes in the market today. However, B. pulchra identification methods have not been well developed. The current study reports a novel real-time PCR method based on TaqMan technology developed for the genetic identification of B. pulchra. The mitochondrial cytochrome oxidase subunit 1 (COI) nucleotide sequences of 29 B. pulchra, 157 skates and rays reported in GenBank DNA database were comparatively analyzed and the COI sequences specific to B. pulchra was identified. Based on this information, a system of specific primers and Minor Groove Binding (MGB) TaqMan probe were designed. The assay successfully discriminated in 29 specimens of B. pulchra and 27 commercial samples with unknown species identity. For B. pulchra DNA, an average Threshold Cycle (Ct) value of 19.1±0.1 was obtained. Among 27 commercial samples, two samples showed average Ct values 19.1±0.0 and 26.7±0.1, respectively and were confirmed to be B. pulchra based on sequencing. The other samples tested showed undetectable or extremely weak signals for the target fragment, which was also consistent with the sequencing results. These results reveal that the method developed is a rapid and efficient tool to identify B. pulchra and might prevent fraud or mislabeling during the distribution of B. pulchra products. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Adenosine Kinase Deficiency in the Brain Results in Maladaptive Synaptic Plasticity.

PubMed

Sandau, Ursula S; Colino-Oliveira, Mariana; Jones, Abbie; Saleumvong, Bounmy; Coffman, Shayla Q; Liu, Long; Miranda-Lourenço, Catarina; Palminha, Cátia; Batalha, Vânia L; Xu, Yiming; Huo, Yuqing; Diógenes, Maria J; Sebastião, Ana M; Boison, Detlev

2016-11-30

Adenosine kinase (ADK) deficiency in human patients (OMIM:614300) disrupts the methionine cycle and triggers hypermethioninemia, hepatic encephalopathy, cognitive impairment, and seizures. To identify whether this neurological phenotype is intrinsically based on ADK deficiency in the brain or if it is secondary to liver dysfunction, we generated a mouse model with a brain-wide deletion of ADK by introducing a Nestin-Cre transgene into a line of conditional ADK deficient Adk fl/fl mice. These Adk Δbrain mice developed a progressive stress-induced seizure phenotype associated with spontaneous convulsive seizures and profound deficits in hippocampus-dependent learning and memory. Pharmacological, biochemical, and electrophysiological studies suggest enhanced adenosine levels around synapses resulting in an enhanced adenosine A 1 receptor (A 1 R)-dependent protective tone despite lower expression levels of the receptor. Theta-burst-induced LTP was enhanced in the mutants and this was dependent on adenosine A 2A receptor (A 2A R) and tropomyosin-related kinase B signaling, suggesting increased activation of these receptors in synaptic plasticity phenomena. Accordingly, reducing adenosine A 2A receptor activity in Adk Δbrain mice restored normal associative learning and contextual memory and attenuated seizure risk. We conclude that ADK deficiency in the brain triggers neuronal adaptation processes that lead to dysregulated synaptic plasticity, cognitive deficits, and increased seizure risk. Therefore, ADK mutations have an intrinsic effect on brain physiology and may present a genetic risk factor for the development of seizures and learning impairments. Furthermore, our data show that blocking A 2A R activity therapeutically can attenuate neurological symptoms in ADK deficiency. A novel human genetic condition (OMIM #614300) that is based on mutations in the adenosine kinase (Adk) gene has been discovered recently. Affected patients develop hepatic encephalopathy, seizures, and severe cognitive impairment. To model and understand the neurological phenotype of the human mutation, we generated a new conditional knock-out mouse with a brain-specific deletion of Adk (Adk Δbrain ). Similar to ADK-deficient patients, Adk Δbrain mice develop seizures and cognitive deficits. We identified increased basal synaptic transmission and enhanced adenosine A 2A receptor (A 2A R)-dependent synaptic plasticity as the underlying mechanisms that govern these phenotypes. Our data show that neurological phenotypes in ADK-deficient patients are intrinsic to ADK deficiency in the brain and that blocking A 2A R activity therapeutically can attenuate neurological symptoms in ADK deficiency. Copyright © 2016 the authors 0270-6474/16/3612118-12$15.00/0.

maxdLoad2 and maxdBrowse: standards-compliant tools for microarray experimental annotation, data management and dissemination.

PubMed

Hancock, David; Wilson, Michael; Velarde, Giles; Morrison, Norman; Hayes, Andrew; Hulme, Helen; Wood, A Joseph; Nashar, Karim; Kell, Douglas B; Brass, Andy

2005-11-03

maxdLoad2 is a relational database schema and Java application for microarray experimental annotation and storage. It is compliant with all standards for microarray meta-data capture; including the specification of what data should be recorded, extensive use of standard ontologies and support for data exchange formats. The output from maxdLoad2 is of a form acceptable for submission to the ArrayExpress microarray repository at the European Bioinformatics Institute. maxdBrowse is a PHP web-application that makes contents of maxdLoad2 databases accessible via web-browser, the command-line and web-service environments. It thus acts as both a dissemination and data-mining tool. maxdLoad2 presents an easy-to-use interface to an underlying relational database and provides a full complement of facilities for browsing, searching and editing. There is a tree-based visualization of data connectivity and the ability to explore the links between any pair of data elements, irrespective of how many intermediate links lie between them. Its principle novel features are: the flexibility of the meta-data that can be captured, the tools provided for importing data from spreadsheets and other tabular representations, the tools provided for the automatic creation of structured documents, the ability to browse and access the data via web and web-services interfaces. Within maxdLoad2 it is very straightforward to customise the meta-data that is being captured or change the definitions of the meta-data. These meta-data definitions are stored within the database itself allowing client software to connect properly to a modified database without having to be specially configured. The meta-data definitions (configuration file) can also be centralized allowing changes made in response to revisions of standards or terminologies to be propagated to clients without user intervention.maxdBrowse is hosted on a web-server and presents multiple interfaces to the contents of maxd databases. maxdBrowse emulates many of the browse and search features available in the maxdLoad2 application via a web-browser. This allows users who are not familiar with maxdLoad2 to browse and export microarray data from the database for their own analysis. The same browse and search features are also available via command-line and SOAP server interfaces. This both enables scripting of data export for use embedded in data repositories and analysis environments, and allows access to the maxd databases via web-service architectures. maxdLoad2 http://www.bioinf.man.ac.uk/microarray/maxd/ and maxdBrowse http://dbk.ch.umist.ac.uk/maxdBrowse are portable and compatible with all common operating systems and major database servers. They provide a powerful, flexible package for annotation of microarray experiments and a convenient dissemination environment. They are available for download and open sourced under the Artistic License.

29 CFR 780.305 - 500 man-day provision.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false 500 man-day provision. 780.305 Section 780.305 Labor...) Statutory Provisions § 780.305 500 man-day provision. (a) Section 3(u) of the Act defines man-day to mean “any day during which an employee performs agricultural labor for not less than 1 hour.” 500 man-days...

29 CFR 780.305 - 500 man-day provision.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 3 2013-07-01 2013-07-01 false 500 man-day provision. 780.305 Section 780.305 Labor...) Statutory Provisions § 780.305 500 man-day provision. (a) Section 3(u) of the Act defines man-day to mean “any day during which an employee performs agricultural labor for not less than 1 hour.” 500 man-days...

29 CFR 780.305 - 500 man-day provision.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 3 2012-07-01 2012-07-01 false 500 man-day provision. 780.305 Section 780.305 Labor...) Statutory Provisions § 780.305 500 man-day provision. (a) Section 3(u) of the Act defines man-day to mean “any day during which an employee performs agricultural labor for not less than 1 hour.” 500 man-days...

29 CFR 780.305 - 500 man-day provision.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 3 2014-07-01 2014-07-01 false 500 man-day provision. 780.305 Section 780.305 Labor...) Statutory Provisions § 780.305 500 man-day provision. (a) Section 3(u) of the Act defines man-day to mean “any day during which an employee performs agricultural labor for not less than 1 hour.” 500 man-days...

The Role of the Nuclear Envelope Protein MAN1 in Mesenchymal Stem Cell Differentiation.

PubMed

Bermeo, Sandra; Al-Saedi, Ahmed; Kassem, Moustapha; Vidal, Christopher; Duque, Gustavo

2017-12-01

Mutations in MAN1, a protein of the nuclear envelope, cause bone phenotypes characterized by hyperostosis. The mechanism of this pro-osteogenic phenotype remains unknown. We increased and decreased MAN1 expression in mesenchymal stem cells (MSC) upon which standard osteogenic and adipogenic differentiation were performed. MAN1 knockdown increased osteogenesis and mineralization. In contrast, osteogenesis remained stable upon MAN1 overexpression. Regarding a mechanism, we found that low levels of MAN1 facilitated the nuclear accumulation of regulatory smads and smads-related complexes, with a concurrently high expression of nuclear β-Catenin. In addition, we found adipogenesis to be decreased in both conditions, although predominantly affected by MAN1 overexpression. Finally, lamin A, a protein of the nuclear envelope that regulates MSC differentiation, was unaffected by changes in MAN1. In conclusion, our studies demonstrated that lower levels of MAN1 in differentiating MSC are associated with higher osteogenesis and lower adipogenesis. High levels of MAN1 only affected adipogenesis. These effects could have an important role in the understanding of the role of the proteins of the nuclear envelope in bone formation. J. Cell. Biochem. 118: 4425-4435, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effect of β-mannanase domain from Trichoderma reesei on its biochemical characters and synergistic hydrolysis of sugarcane bagasse.

PubMed

Ma, Lijuan; Ma, Qing; Cai, Rui; Zong, Zhiyou; Du, Liping; Guo, Gaojie; Zhang, Yingying; Xiao, Dongguang

2018-05-01

β-mannanase is a key enzyme for hydrolyzing mannan, a major constituent of hemicellulose, which is the second most abundant polysaccharide in nature. Different structural domains greatly affect its biochemical characters and catalytic efficiency. However, the effects of linker and carbohydrate-binding module (CBM) on β-mannanase from Trichoderma reesei (Man1) have not yet been fully described. The present study aimed to determine the influence of different domains on the expression efficiency, biochemical characteristics and hemicellulosic deconstruction of Man1. The expression efficiency was improved after truncating CBM. Activities of Man1 and Man1ΔCBM (CBM) in the culture supernatant after 168 h of induction were 34.5 and 42.9 IU mL -1 , although a value of only 0.36 IU mL -1 was detected for Man1ΔLCBM (lacking CBM and linker). Man1 showed higher thermostability than Man1ΔCBM at low temperature, whereas Man1ΔCBM had a higher specificity for galactomannan (K m  = 2.5 mg mL -1 ) than Man1 (K m  = 4.0 mg mL -1 ). Both Man1 and Man1ΔCBM could synergistically improve the hydrolysis of cellulose, galactomannan and pretreated sugarcane bagasse, with a 10-30% improvement of the reducing sugar yield. Linker and CBM domains were vital for mannanase activity and expression efficiency. CBM affected the thermostability and adsorption ability of Man1. The results obtained in the present study should help guide the rational design and directional modification of Man with respect to improving its catalytic efficiency. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Genome mining and motif truncation of glycoside hydrolase family 5 endo-β-1,4-mannanase encoded by Aspergillus oryzae RIB40 for potential konjac flour hydrolysis or feed additive.

PubMed

Tang, Cun-Duo; Shi, Hong-Ling; Tang, Qing-Hai; Zhou, Jun-Shi; Yao, Lun-Guang; Jiao, Zhu-Jin; Kan, Yun-Chao

2016-11-01

Two novel glycosyl hydrolase family 5 (GH5) β-mannanases (AoMan5A and AoMan5B) were identified from Aspergillus oryzae RIB40 by genome mining. The AoMan5A contains a predicted family 1 carbohydrate binding module (CBM-1), located at its N-terminal. The AoMan5A, AoMan5B and truncated mutant AoMan5AΔCL (truncating the N-terminal CBM and linker of AoMan5A) were expressed retaining the N-terminus of the native protein in Pichia pastoris GS115 by pPIC9K M . The specific enzyme activity of the purified reAoMan5A, reAoMan5B and reAoMan5AΔCL towards locust bean gum at pH 3.6 and 40°C for 10min, was 8.3, 104.2 and 15.8U/mg, respectively. The temperature properties of the reAoMan5AΔCL were improved by truncating CBM. They can degrade the pretreated konjac flour and produce prebiotics. In addition, they had excellent stability under simulative gastric fluid and simulative prilling process. All these properties make these recombinant β-mannanases potential additives for use in the food and feed industries. Copyright © 2016. Published by Elsevier Inc.

European perspectives on regional estimates of standing water bodies and the relevance of man-made ponds

NASA Astrophysics Data System (ADS)

Terasmaa, Jaanus; Bartout, Pascal; Marzecova, Agata; Touchart, Laurent; Koff, Tiiu; Choffel, Quentin; Kapanen, Galina; Maleval, Véronique; Millot, Camille; Qsair, Zoubida; Vandel, Egert

2015-04-01

Until recently, the small water bodies have been disregarded in the environmental management and protection policies. For example, the European Water Framework Directive 2000/60/EC proposes the threshold surface area of water bodies for typology and reporting as 50 ha. The inventories on state level or scientific studies took into account smaller water bodies (e.g. <10 ha for Meybeck, 1995, <1 ha for Rjanžin, 2005, or <0.05 ha for Kuusisto and Raatikainen, 1988) but these methods of estimations has been region-specific and not suitable for global estimates. The increasing awareness about the important roles that terrestrial standing water bodies play in the biodiversity or hydrological and biogeochemical cycles has facilitated new global and regional inventories of lakes and water bodies. Although with differences in the total counts and in the statistical estimates of abundance-size relationship, these recent global estimates reveal the quantitative importance of the terrestrial standing water bodies in the global hydrology (Downing et al., 2006; Verpoorter et al., 2014). Yet, our analysis of the abundance and distribution EU water bodies suggest that these global counts underrepresents the hydrologically complex terrain of the European territory. One of the main limits is the high cutoff limit that excludes small water bodies below ~0.2 ha. For example, in France, Bartout and Touchart (2013) report that including water bodies below 0.01 ha in the estimates resulted in 16 times higher number of water bodies with the surface area one-third higher than officially registered inventories. Also, in Estonia, the water bodies with a surface area below 1 ha are almost 50 times more abundant than those above 1 ha and 92% of all standing water bodies are smaller than 0.2 ha. Using the OpenStreetMap database we will discuss the differences between global inventories and EU-level analysis. We will show the alternative regional estimates of water bodies with the surface size threshold limit 0.01 ha which will illustrate the quantitative importance of very small often man-made ponds, which are however, abundant cultural heritage in many parts of Europe. Secondly, by comparing detailed national inventories compiled for France and Estonia, we will introduce usefulness of the the 'local to global' approach in which the local databases may significantly strengthen the precision of the regional (EU) level analysis. Overall, we will disss that all standing water bodies - including small and man-made ponds - play an important role in ecosystem services and require careful management to avoid hydrological and environmental deterioration. References: Verpoorter et al. (2014) Geophysical Research Letters, 41. Bartout & Touchart,(2013) Annales de Géographie, 691. Downing et al., (2006) Limnology and Oceanography, 51(5). Kuusisto & Raatikainen, (1988) Terra, 102. Meybeck, (1995) in Lerman et al., Physics and chemistry of lakes. Rjanžin, (2005) Priroda, 4.

75 FR 52724 - Procurement List Additions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-27

...: 8405-00-FAB-0201--Man's, S/S, Air Force Shade 1550, Size 13\\1/ 2\\ NSN: 8405-00-FAB-0202--Man's, S/S, Air Force Shade 1550, Size 14 NSN: 8405-00-FAB-0203--Man's, S/S, Air Force Shade 1550, Size 14 \\1/ 2\\ NSN: 8405-00-FAB-0204--Man's, S/S, Air Force Shade 1550, Size 15 NSN: 8405-00-FAB-0212--Man's, S/S...

Traditional manual acupuncture combined with rehabilitation therapy for shoulder hand syndrome after stroke within the Chinese healthcare system: a systematic review and meta-analysis.

PubMed

Peng, Le; Zhang, Chao; Zhou, Lan; Zuo, Hong-Xia; He, Xiao-Kuo; Niu, Yu-Ming

2018-04-01

To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke. PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies. Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software. A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I 2  = 71%, P = 0.0005). Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

Outcomes for jejunal interposition reconstruction compared with Roux-en-Y anastomosis: A meta-analysis.

PubMed

Fan, Kai-Xi; Xu, Zhong-Fa; Wang, Mei-Rong; Li, Dao-Tang; Yang, Xiang-Shan; Guo, Jing

2015-03-14

To compare the clinical outcomes between jejunal interposition reconstruction and Roux-en-Y anastomosis after total gastrostomy in patients with gastric cancer. A systematic literature search was conducted by two independent researchers on PubMed, EMBASE, the Cochrane Library, Google Scholar, and other English literature databases, as well as the Chinese Academic Journal, Chinese Biomedical Literature Database, and other Chinese literature databases using "Gastrostomy", "Roux-en-Y", and "Interposition" as keywords. Data extraction and verification were performed on the literature included in this study. RevMan 5.2 software was used for data processing. A fixed-effects model was applied in the absence of heterogeneity between studies. A random effects model was applied in the presence of heterogeneity between studies. Ten studies with a total of 762 gastric cancer patients who underwent total gastrostomy were included in this study. Among them, 357 received jejunal interposition reconstruction after total gastrostomy, and 405 received Roux-en-Y anastomosis. Compared with Roux-en-Y anastomosis, jejunal interposition reconstruction significantly decreased the incidence of dumping syndrome (OR = 0.18, 95%CI: 0.10-0.31; P < 0.001), increased the prognostic nutritional index [weighted mean difference (WMD) = 6.02, 95%CI: 1.82-10.22; P < 0.001], and improved the degree of postoperative weight loss [WMD = 2.47, 95%CI: -3.19-(-1.75); P < 0.001]. However, there is no statistically significant difference in operative time, hospital stay, or incidence of reflux esophagitis. Compared with Roux-en-Y anastomosis, patients who underwent jejunal interposition reconstruction after total gastrostomy had a lower risk of postoperative long-term complications and improved life quality.

Reciprocal relationship between alpha1,2 mannosidase processing and reglucosylation in the rough endoplasmic reticulum of Man-P-Dol deficient cells.

PubMed

Duvet, S; Chirat, F; Mir, A M; Verbert, A; Dubuisson, J; Cacan, R

2000-02-01

The study of the glycosylation pathway of a mannosylphosphoryldolichol-deficient CHO mutant cell line (B3F7) reveals that truncated Glc(0-3)Man5GlcNAc2 oligosaccharides are transferred onto nascent proteins. Pulse-chase experiments indicate that these newly synthesized glycoproteins are retained in intracellular compartments and converted to Man4GlcNAc2 species. In this paper, we demonstrate that the alpha1,2 mannosidase, which is involved in the processing of Man5GlcNAc2 into Man4GlcNAc2, is located in the rough endoplasmic reticulum. The enzyme was shown to be inhibited by kifunensine and deoxymannojirimycin, indicating that it is a class I mannosidase. In addition, Man4GlcNAc2 species were produced at the expense of Glc1Man5GlcNAc2 species. Thus, the trimming of Man5GlcNAc2 to Man4GlcNAc2, which is catalyzed by this mannosidase, could be involved in the control of the glucose-dependent folding pathway.

[Alkaline-adapted beta-mannanase of Bacillus pumilus: gene heterologous expression and enzyme characterization].

PubMed

Tang, Jiajie; Guo, Su; Wang, Wei; Wei, Wei; Wei, Dongzhi

2015-11-04

We expressed a novel alkaline-adapted beta-mannanase gene and characterized the enzyme for potential industrial applications. We obtained a mannanase gene (named man(B)) from Bacillus pumilus Nsic2 and expressed the gene man(B) in Escherichia coli and Bacillus subtilis. Furthermore, we characterized the enzyme. The gene man(B) had an open reading frame of 1104 bp that encoded a polypeptide of 367-amino-acid beta-mannanase (Man(B)). The protein sequence showed the highest identity with the beta-mannanase from B. pumilus CCAM080065. We expressed the gene man(B) in E. coli BL21 (DE3) with the enzyme activity of 11021.3 U/mL. Compared with other mannanases, Man(B) showed higher stability under alkaline conditions and was stable at pH6.0 -9.0. The specific activity of purified Man(B) was 4191 ± 107 U/mg. The K(m) and V(max) values of purified Man(B) were 35.7 mg/mL and 14.9 μmol/(mL x min), respectively. Meanwhile, we achieved recombinant protein secretion expression in B. subtilis WB800N. We achieved heterologous expression of the gene man(B) and characterized its enzyme. The alkaline-adapted Man(B) showed potential value in industrial applications due to its pH stability.

Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins.

PubMed

Larsen, Ida Signe Bohse; Narimatsu, Yoshiki; Joshi, Hiren Jitendra; Siukstaite, Lina; Harrison, Oliver J; Brasch, Julia; Goodman, Kerry M; Hansen, Lars; Shapiro, Lawrence; Honig, Barry; Vakhrushev, Sergey Y; Clausen, Henrik; Halim, Adnan

2017-10-17

The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3.

Structural and biochemical insights into the substrate-binding mechanism of a novel glycoside hydrolase family 134 β-mannanase.

PubMed

You, Xin; Qin, Zhen; Li, Yan-Xiao; Yan, Qiao-Juan; Li, Bin; Jiang, Zheng-Qiang

2018-06-01

Mannan is one of the major constituent groups of hemicellulose, which is a renewable resource from higher plants. β-Mannanases are enzymes capable of degrading lignocellulosic biomass. Here, an endo-β-mannanase from Rhizopus microsporus (RmMan134A) was cloned and expressed. The recombinant RmMan134A showed maximal activity at pH 5.0 and 50 °C, and exhibited high specific activity towards locust bean gum (2337 U/mg). To gain insight into the substrate-binding mechanism of RmMan134A, four complex structures (RmMan134A-M3, RmMan134A-M4, RmMan134A-M5 and RmMan134A-M6) were further solved. These structures showed that there were at least seven subsites (-3 to +4) in the catalytic groove of RmMan134A. Mannose in the -1 subsite hydrogen bonded with His113 and Tyr131, revealing a unique conformation. Lys48 and Val159 formed steric hindrance, which impedes to bond with galactose branches. In addition, the various binding modes of RmMan134A-M5 indicated that subsites -2 to +2 are indispensable during the hydrolytic process. The structure of RmMan134A-M4 showed that mannotetrose only binds at subsites +1 to +4, and RmMan134A could therefore not hydrolyze mannan oligosaccharides with degree of polymerization ≤4. Through rational design, the specific activity and optimal conditions of RmMan134A were significantly improved. The purpose of this paper is to investigate the structure and function of fungal GH family 134 β-1,4-mannanases, and substrate-binding mechanism of GH family 134 members. Copyright © 2018 Elsevier B.V. All rights reserved.

Digital dream analysis: a revised method.

PubMed

Bulkeley, Kelly

2014-10-01

This article demonstrates the use of a digital word search method designed to provide greater accuracy, objectivity, and speed in the study of dreams. A revised template of 40 word search categories, built into the website of the Sleep and Dream Database (SDDb), is applied to four "classic" sets of dreams: The male and female "Norm" dreams of Hall and Van de Castle (1966), the "Engine Man" dreams discussed by Hobson (1988), and the "Barb Sanders Baseline 250" dreams examined by Domhoff (2003). A word search analysis of these original dream reports shows that a digital approach can accurately identify many of the same distinctive patterns of content found by previous investigators using much more laborious and time-consuming methods. The results of this study emphasize the compatibility of word search technologies with traditional approaches to dream content analysis. Copyright © 2014 Elsevier Inc. All rights reserved.

NASA's X-Plane Database and Parametric Cost Model v 2.0

NASA Technical Reports Server (NTRS)

Sterk, Steve; Ogluin, Anthony; Greenberg, Marc

2016-01-01

The NASA Armstrong Cost Engineering Team with technical assistance from NASA HQ (SID)has gone through the full process in developing new CERs from Version #1 to Version #2 CERs. We took a step backward and reexamined all of the data collected, such as dependent and independent variables, cost, dry weight, length, wingspan, manned versus unmanned, altitude, Mach number, thrust, and skin. We used a well- known statistical analysis tool called CO$TAT instead of using "R" multiple linear or the "Regression" tool found in Microsoft Excel(TradeMark). We setup an "array of data" by adding 21" dummy variables;" we analyzed the standard error (SE) and then determined the "best fit." We have parametrically priced-out several future X-planes and compared our results to those of other resources. More work needs to be done in getting "accurate and traceable cost data" from historical X-plane records!

Identification and description of low-molecular weight chemicals inducing hypersensitivity in man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mari, A.; Misiti, D.; Dorello-Misiti, P.

1988-10-01

The purpose of this study is to compose a list of allergenic chemicals. Each chemical is described in a monograph. The objective of such a monograph program is to collect from the international scientific literature available relevant experimental, chemical, and epidemiological data on chemicals to which humans are known to be exposed and sensitized. A list of 721 chemicals, with related synonyms and trade names, that induce allergic responses and hypersensitivities was prepared. The chemicals were selected on the basis of evidence of human exposure and sensitization. Each monograph contains several data considered relevant to the evaluation of the sensitizingmore » hazards of chemical substances. The data are divided in three sections: chemical identity, sensitizing power, and occurrence. All the data contained in the monographs along with the references and the synonyms are stored in a database application computer program. Preliminary results of 308 of 721 monographs analyzed are reported.« less

Weekly Versus Triweekly Cisplatin-Based Chemotherapy Concurrent With Radiotherapy in the Treatment of Cervical Cancer: A Meta-Analysis.

PubMed

Chen, Xingxing; Zou, Haizhou; Li, Huifang; Lin, Ruifang; Su, Meng; Zhang, Wenyi; Zhou, Yongqiang; Zhang, Ping; Hou, Meng; Deng, Xia; Zou, Changlin

2017-02-01

The aim of this study was to evaluate toxicity, compliance, recurrence and the survival of weekly and triweekly cisplatin-based concomitant chemoradiation in treatment of cervical cancer. The databases were searched from 1995 until 2015 to identify eligible studies on weekly versus triweekly cisplatin chemoradiotherapy. The data were analyzed by RevMan 5.3 software. A total of 5 randomized controlled trials were included in this review. Weekly cisplatin regimen significantly reduced the incidence of Hematologic toxicity. However, there was no significantly different between the 2 arms in compliance, recurrence and the survival rate (all P >0.05). Weekly cisplatin regimen had the similar therapeutic effect as the triweekly cisplatin regimen but with less hematologic toxicity. Therefore, we recommend the weekly cisplatin 30 to 40 mg/m chemoradiotherapy as the strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.

An Exploration of Integrated Ground Weapons Concepts for Armor/Anti- Armor Missions

DTIC Science & Technology

1991-01-01

de - vii signs. We examined the potential of these light armor designs closely, but did not compare them with the MBT designs. The main problem in...man MBT .............................. 93 35. Three-man remote turret des :6n: side view ............................ 95 36. Three-man remote turret...configurations, including two- and three-man ver- sions with remote and manned turrets. Section V describes some light armored vehicle de - signs, including two

Altitude Chamber Testing of the Passenger Oxygen System (POS)

DTIC Science & Technology

2009-08-01

4 5.0 Schedule 4 6.0 Method for Unmanned Testing 4 7.0 Unmanned Testing Results 6 8.0 Methods for Manned...manned testing. 30 Mar 09: Subjects received orientation and training briefings. 31 Mar-03 Apr 09: POS manned testing conducted. 6.0 Method ...8.0 Methods for Manned Testing: The system was tested in five manned modes. The details of each mode are described in Appendix B (ICD for

Glycosylation and processing of high-mannose oligosaccharides of thyroid-stimulating hormone subunits: comparison to nonsecretory cell glycoproteins.

PubMed

Ronin, C; Stannard, B S; Rosenbloom, I L; Magner, J A; Weintraub, B D

1984-09-25

Thyroid-stimulating hormone (TSH) subunit glycosylation was compared to that of total cell glycoproteins in mouse thyrotropic tumors. Lipid-linked oligosaccharides, total cell glycoproteins, and TSH subunits were labeled with either [3H]mannose, [3H]galactose, or [3H]glucose in pulse and pulse-chase experiments. The various oligosaccharides were isolated respectively by lipid extraction and mild acid hydrolysis, by selective immunoprecipitation, or by acid precipitation followed by trypsin and endoglycosidase H treatment. The nature of the oligosaccharides was assessed by their migration in paper chromatography, their relative incorporation of different precursors, and also their resistance to alpha-mannosidase. At 60 min, lipid-linked oligosaccharides were found to be composed of Glc3-2Man9GlcNAc2, Man9-8GlcNAc2, and Man5GlcNAc2. At 10 or 60 min of labeling, total cell proteins contained Glc3Man9GlcNAc2, Glc1Man9GlcNAc2, Man9GlcNAc2, Glc1Man8GlcNAc2, Man8GlcNAc2, and Man7GlcNAc2. The largest oligosaccharide, Glc3Man9GlcNAc2, had an unusually long half-life of about 2 h. In contrast, no Glc3Man9GlcNAc2 was found either on TSH + alpha subunits or on free beta subunits isolated either by immunoprecipitation or by sodium dodecyl sulfate gel electrophoresis. Instead, primarily Man9GlcNAc2 was found after a 10-min pulse both on TSH + alpha subunits and on beta subunits. When the pulse was followed by a chase up to 2 h, there was a progressive increase in Man8GlcNAc2 in higher amounts on TSH + alpha-subunit carbohydrate chains than on beta subunits.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcomes of repeat catheter ablation using magnetic navigation or conventional ablation.

PubMed

Akca, Ferdi; Theuns, Dominic A M J; Abkenari, Lara Dabiri; de Groot, Natasja M S; Jordaens, Luc; Szili-Torok, Tamas

2013-10-01

After initial catheter ablation, repeat procedures could be necessary. This study evaluates the efficacy of the magnetic navigation system (MNS) in repeat catheter ablation as compared with manual conventional techniques (MANs). The results of 163 repeat ablation procedures were analysed. Ablations were performed either using MNS (n = 84) or conventional manual ablation (n = 79). Procedures were divided into four groups based on the technique used during the initial and repeat ablation procedure: MAN-MAN (n = 66), MAN-MNS (n = 31), MNS-MNS (n = 53), and MNS-MAN (n = 13). Three subgroups were analysed: supraventricular tachycardias (SVTs, n = 68), atrial fibrillation (AF, n = 67), and ventricular tachycardias (VT, n = 28). Recurrences were assessed during 19 ± 11 months follow-up. Overall, repeat procedures using MNS were successful in 89.0% as compared with 96.2% in the MAN group (P = ns). The overall recurrence rate was significantly lower using MNS (25.0 vs. 41.4%, P = 0.045). Acute success and recurrence rates for the MAN-MAN, MAN-MNS, MNS-MNS, and MNS-MAN groups were comparable. For the SVT subgroup a higher acute success rate was achieved using MAN (87.9 vs. 100.0%, P = 0.049). The use of MNS for SVT is associated with longer procedure times (205 ± 82 vs. 172 ± 69 min, P = 0.040). For AF procedure and fluoroscopy times were longer (257 ± 72 vs. 185 ± 64, P = 0.001; 59.5 ± 19.3 vs. 41.1 ± 18.3 min, P < 0.001). Less fluoroscopy was used for MNS-guided VT procedures (22.8 ± 14.7 vs. 41.2 ± 10.9, P = 0.011). Our data suggest that overall MNS is comparable with MAN in acute success after repeat catheter ablation. However, MNS is related to fewer recurrences as compared with MAN.

Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.

PubMed

Eklund, Erik A; Merbouh, Nabyl; Ichikawa, Mie; Nishikawa, Atsushi; Clima, Jessica M; Dorman, James A; Norberg, Thomas; Freeze, Hudson H

2005-11-01

Patients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients.

Mannose Induces an Endonuclease Responsible for DNA Laddering in Plant Cells

PubMed Central

Stein, Joshua C.; Hansen, Geneviève

1999-01-01

The effect of d-mannose (Man) on plant cells was studied in two different systems: Arabidopsis roots and maize (Zea mays) suspension-cultured cells. In both systems, exposure to d-Man was associated with a subset of features characteristic of apoptosis, as assessed by oligonucleosomal fragmentation and microscopy analysis. Furthermore, d-Man induced the release of cytochrome c from mitochondria. The specificity of d-Man was evaluated by comparing the effects of diastereomers such as l-Man, d-glucose, and d-galactose. Of these treatments, only d-Man caused a reduction in final fresh weight with concomitant oligonucleosomal fragmentation. Man-induced DNA laddering coincided with the activation of a DNase in maize cytosolic extracts and with the appearance of single 35-kD band detected using an in-gel DNase assay. The DNase activity was further confirmed by using covalently closed circular plasmid DNA as a substrate. It appears that d-Man, a safe and readily accessible compound, offers remarkable features for the study of apoptosis in plant cells. PMID:10482662

Genetically Encoded Fragment-Based Discovery of Glycopeptide Ligands for Carbohydrate-Binding Proteins

DOE PAGES

Ng, Simon; Lin, Edith; Kitov, Pavel I.; ...

2015-04-10

Here we describe an approach to accelerate the search for competitive inhibitors for carbohydrate-recognition domains (CRDs). Genetically encoded fragment-based-discovery (GE-FBD) uses selection of phagedisplayed glycopeptides to dock a glycan fragment at the CRD and guide selection of Synergistic peptide motifs adjacent to the CRD. Starting from concanavalin A (ConA), a mannose (Man)-binding protein, as a bait, we narrowed a library of 10 8 glycopeptides to 86 leads that share a consensus motif, Man-WYD. Validation of synthetic leads yielded Man-WYDLF that exhibited 40 50-fold enhancement in affinity over methyl α-D-mannopyranoside (MeMan). Lectin array Suggested specificity: Man-WYD derivative bound only to 3more » out of 17 proteins-ConA, LcH, and PSA-that bind to Man. An X-ray structure of ConA.:Man-WYD proved that the trimannoside core and Man-WYD exhibit identical CRD docking; but their extra-CRD binding modes are significantly. different. Still, they have comparable affinity and selectivity for various Man-binding proteins. The intriguing observation provides new insight into functional mimicry :of carbohydrates by peptide ligands. GE-FBD may provide an alternative to rapidly search for competitive inhibitors for lectins.« less

Genetically Encoded Fragment-Based Discovery of Glycopeptide Ligands for Carbohydrate-Binding Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, Simon; Lin, Edith; Kitov, Pavel I.

Here we describe an approach to accelerate the search for competitive inhibitors for carbohydrate-recognition domains (CRDs). Genetically encoded fragment-based-discovery (GE-FBD) uses selection of phagedisplayed glycopeptides to dock a glycan fragment at the CRD and guide selection of Synergistic peptide motifs adjacent to the CRD. Starting from concanavalin A (ConA), a mannose (Man)-binding protein, as a bait, we narrowed a library of 10 8 glycopeptides to 86 leads that share a consensus motif, Man-WYD. Validation of synthetic leads yielded Man-WYDLF that exhibited 40 50-fold enhancement in affinity over methyl α-D-mannopyranoside (MeMan). Lectin array Suggested specificity: Man-WYD derivative bound only to 3more » out of 17 proteins-ConA, LcH, and PSA-that bind to Man. An X-ray structure of ConA.:Man-WYD proved that the trimannoside core and Man-WYD exhibit identical CRD docking; but their extra-CRD binding modes are significantly. different. Still, they have comparable affinity and selectivity for various Man-binding proteins. The intriguing observation provides new insight into functional mimicry :of carbohydrates by peptide ligands. GE-FBD may provide an alternative to rapidly search for competitive inhibitors for lectins.« less

Building a database on geological hazards in karst: some considerations about certainty, accuracy and reliability in the collection of data

NASA Astrophysics Data System (ADS)

Parise, Mario; Vennari, Carmela

2015-04-01

Sinkholes are definitely the most typical geohazard affecting karst territories. Even though typically their formation is related to an underground cave, and the related subterranean drainage, sinkholes can also be observed on non-soluble deposits such as alluvial and/or colluvial materials. Further, the presence of cavities excavated by man (for different purposes, and in different ages) may be at the origin of other phenomena of sinkholes, the so-called anthropogenic sinkholes, that characterize many historical centres of built-up areas. In Italy, due to the long history of the country, these latter, too, are of great importance, being those that typically involve human buildings and infrastructures, and cause damage and losses to society. As for any other geohazard, building a database through collection of information on the past events is a mandatory step to start the analyses aimed at the evaluation of susceptibility, hazard, and risk. The Institute of Research for the Hydrological Protection (IRPI) of the National Research Council of Italy (CNR) has been working in the last years at the construction of a specific chronological database on sinkholes in the whole country. In the database, the natural and anthropogenic sinkholes are treated in two different subsets, given the strong differences existing as regards both the causal and triggering factors, and the stabilization works as well. A particular care was given in the database to the precise site and date of occurrence of the events, as crucial information for assessing, respectively, the susceptibility and the hazard related to the particular phenomenon under study. As a requirement to be included in the database, a temporal reference of the sinkhole occurrence must be therefore known. Certainty in the geographical position of the event is a fundamental information to correctly locate the sinkhole, and to develop geological and morphological considerations aimed at performing a susceptibility analysis. This factor does not have to be disregarded since, especially for the most ancient events, the data from the sources may be not of high precision for a correct positioning of the sinkhole site. As a consequence, each sinkhole in the database was ranked according to the degree of certainty in the location, subdivided into three different levels. Accuracy of the date of occurrence of the sinkhole was then evaluated, and the highest accuracy was assigned when all the information required (hour, day, month and year of occurrence) were available. The temporal reference is of crucial importance in the IRPI database, since the final goal of the research project is the definition of the sinkhole hazard in Italy. In order to reach such goal, given the definition of hazard, the time of occurrence, and the most likely return time of the events have to be assessed. Overall, the aforementioned elements of the database allow to make some considerations about the reliability of the information presented, their precision, and to give the correct weight to the outcomes deriving from its analyses. Such issues are discussed in the present contribution, as crucial elements that need to be clearly defined in a scientifically-sound database. The database has reached so far about 900 events (31% natural sinkholes and 48% anthropogenic sinkholes, whilst 21% of sinkholes have an uncertain origin). It is continuously updated, and represents a good starting point for analysis of the sinkhole hazard at the national scale, aimed at increasing the level of attention by scientists, practitioners and authorities on this subtle hazard.

Man-systems distributed system for Space Station Freedom

NASA Technical Reports Server (NTRS)

Lewis, J. L.

1990-01-01

Viewgraphs on man-systems distributed system for Space Station Freedom are presented. Topics addressed include: description of man-systems (definition, requirements, scope, subsystems, and topologies); implementation (approach, tools); man-systems interfaces (system to element and system to system); prime/supporting development relationship; selected accomplishments; and technical challenges.

33 CFR 146.120 - Manning of survival craft.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Manning of survival craft. 146.120 Section 146.120 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES OPERATIONS Manned OCS Facilities § 146.120 Manning of survival...

33 CFR 146.120 - Manning of survival craft.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Manning of survival craft. 146.120 Section 146.120 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES OPERATIONS Manned OCS Facilities § 146.120 Manning of survival...

33 CFR 146.120 - Manning of survival craft.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Manning of survival craft. 146.120 Section 146.120 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES OPERATIONS Manned OCS Facilities § 146.120 Manning of survival...

33 CFR 146.120 - Manning of survival craft.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Manning of survival craft. 146.120 Section 146.120 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES OPERATIONS Manned OCS Facilities § 146.120 Manning of survival...

Nucleolin is a nuclear target of heparan sulfate derived from glypican-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Fang; Belting, Mattias; Fransson, Lars-Åke

The recycling, S-nitrosylated heparan sulfate (HS) proteoglycan glypican-1 releases anhydromannose (anMan)-containing HS chains by a nitrosothiol-catalyzed cleavage in endosomes that can be constitutive or induced by ascorbate. The HS-anMan chains are then transported to the nucleus. A specific nuclear target for HS-anMan has not been identified. We have monitored endosome-to-nucleus trafficking of HS-anMan by deconvolution and confocal immunofluorescence microscopy using an anMan-specific monoclonal antibody in non-growing, ascorbate-treated, and growing, untreated, wild-type mouse embryonic fibroblasts and hypoxia-exposed Alzheimer mouse Tg2576 fibroblasts and human U87 glioblastoma cells. In all cells, nuclear HS-anMan targeted a limited number of sites of variable size wheremore » it colocalized with DNA and nucleolin, an established marker for nucleoli. HS-anMan also colocalized with ethynyl uridine-tagged nascent RNA and two acetylated forms of histone H3. Acute hypoxia increased the formation of HS-anMan in both Tg2576 and U87 cells. A portion of HS-anMan colocalized with nucleolin at small discrete sites, while most of the nucleolin and nascent RNA was dispersed. In U87 cells, HS-anMan, nucleolin and nascent RNA reassembled after prolonged hypoxia. Nucleolar HS may modulate synthesis and/or release of rRNA.« less

High-level expression of two thermophilic β-mannanases in Yarrowialipolytica.

PubMed

YaPing, Wang; Ben, Rao; Ling, Zhang; Lixin, Ma

2017-05-01

Two thermophilic β-mannanases (ManA and ManB)were successfully expressed in Yarrowialipolytica using vector pINA1296I. The sequences of manA from Aspergillus niger CBS 513.88 and manB from Bacillus subtilis BCC41051 were optimized based on codon-usage bias in Y.lipolytica and synthesized by overlapping polymerase chain reaction (PCR). We utilized the pINA1296I vector, which allows inserting and expression of multiple copies of an expression cassette, to engineer recombinant strains containing multiple copies of manA or manB. Following verification of target-gene expression by quantitative PCR, fermentation experiments indicated that recombinant protein levels and enzyme activity increased along with increasing manA/manB copy number.After production in a 10 l fermenter, we obtained maximum enzyme activity from strains YLA6 and YLB6 of3024 U/mL and 1024 U/mL, respectively. Additionally, purification and characterization results revealed that the optimum pH and temperature for manA activity were pH∼5 and ∼70 °C, and for manB activity were pH∼7 and 60 °C, respectively. These results indicated that the thermo stabilities of these two enzymes were higher than most other mannanases, making them potentially useful for industrial applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins

PubMed Central

Larsen, Ida Signe Bohse; Narimatsu, Yoshiki; Siukstaite, Lina; Harrison, Oliver J.; Brasch, Julia; Goodman, Kerry M.; Hansen, Lars; Shapiro, Lawrence; Honig, Barry; Vakhrushev, Sergey Y.; Clausen, Henrik

2017-01-01

The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1–4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3. PMID:28973932

Fused man-machine classification schemes to enhance diagnosis of breast microcalcifications

NASA Astrophysics Data System (ADS)

Andreadis, Ioannis; Sevastianos, Chatzistergos; George, Spyrou; Konstantina, Nikita

2017-11-01

Computer aided diagnosis (CAD x ) approaches are developed towards the effective discrimination between benign and malignant clusters of microcalcifications. Different sources of information are exploited, such as features extracted from the image analysis of the region of interest, features related to the location of the cluster inside the breast, age of the patient and descriptors provided by the radiologists while performing their diagnostic task. A series of different CAD x schemes are implemented, each of which uses a different category of features and adopts a variety of machine learning algorithms and alternative image processing techniques. A novel framework is introduced where these independent diagnostic components are properly combined according to features critical to a radiologist in an attempt to identify the most appropriate CAD x schemes for the case under consideration. An open access database (Digital Database of Screening Mammography (DDSM)) has been elaborated to construct a large dataset with cases of varying subtlety, in order to ensure the development of schemes with high generalization ability, as well as extensive evaluation of their performance. The obtained results indicate that the proposed framework succeeds in improving the diagnostic procedure, as the achieved overall classification performance outperforms all the independent single diagnostic components, as well as the radiologists that assessed the same cases, in terms of accuracy, sensitivity, specificity and area under the curve following receiver operating characteristic analysis.

The effects of different rates of ascent on the incidence of altitude decompression sickness

NASA Technical Reports Server (NTRS)

Kumar, K. V.; Waligora, James M.

1989-01-01

The effect of different rates of ascent on the incidence of altitude decompression sickness (DCS) was analyzed by a retrospective study on 14,123 man-flights involving direct ascent up to 38,000 ft altitude. The data were classified on the basis of altitude attained, denitrogenation at ground level, duration of stay at altitude, rest or exercise while at altitude, frequency of exercise at altitude, and ascent rates. This database was further divided on the basis of ascent rates into different groups from 1000 ft/min up to 53,000 ft/min. The database was analyzed using multiple correlation and regression methods, and the results of the analysis reveal that ascent rates influence the incidence of DCS in combination with the various factors mentioned above. Rate of ascent was not a significant predictor of DCS and showed a low, but significant multiple correlation (R=0.31) with the above factors. Further, the effects of rates below 2500 ft/min are significantly different from that of rates above 2500 ft/min on the incidence of symptoms (P=0.03) and forced descent (P=0.01). At rates above 2500 ft/min and up to 53,000 ft/min, the effects of ascent rates are not significantly different (P greater than 0.05) in the population examined while the effects of rates below 2500 ft/min are not clear.

Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

PubMed Central

Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.

2013-01-01

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

Impact of operation details on hydrocephalus after decompressive craniectomy

PubMed Central

Wang, Qiang-Ping; Ma, Jun-Peng; Zhou, Zhang-Ming; You, Chao

2016-01-01

Objective: To evaluate the correlation between the distance of craniectomy from the midline and hydrocephalus after DC. Methods: The following electronic databases were searched from their inception to June 2015: Cochrane Library, MEDLINE, Science Direct, EMBASE, Scopus, Google Scholar, the Chinese Biomedical Database (CBM), and the Chinese National Knowledge Infrastructure (CNKI). All randomized clinical trials, prospective cohort, retrospective observational cohort, and case-control studies investigating the relationship between distance of craniectomy from the midline and hydrocephalus after DC were enrolled. The Cochrane Collaboration’s software RevMan 5.3 was used for meta-analysis. Results: Six retrospective cohort studies involving 462 participants were included. Pooled analysis of 4 studies suggested that craniectomy close to the midline (<25 mm) was associated with a significantly increased risk of postoperative hydrocephalus (odds ratio [OR] = 3.61, 95% confidence interval [CI]: 1.3 - 9.97, p=0.01). However, meta-analysis of 4 studies did not find statistical differences when comparing the distance of craniectomy from the midline in the hydrocephalus group and that in the non-hydrocephalus group (OR = −0.14, 95% CI: −0.44 - 0.15, p=0.34). Conclusions: Available evidence was insufficient to support the theory that craniectomy close to the midline increases the risk of developing hydrocephalus after DC. Well-conducted randomized clinical trials are required to verify this issue. PMID:26818161

Storm-centric view of Tropical Cyclone oceanic wakes

NASA Astrophysics Data System (ADS)

Gentemann, C. L.; Scott, J. P.; Smith, D.

2012-12-01

Tropical cyclones (TCs) have a dramatic impact on the upper ocean. Storm-generated oceanic mixing, high amplitude near-inertial currents, upwelling, and heat fluxes often warm or cool the surface ocean temperatures over large regions near tropical cyclones. These SST anomalies occur to the right (Northern Hemisphere) or left (Southern Hemisphere) of the storm track, varying along and across the storm track. These wide swaths of temperature change have been previously documented by in situ field programs as well as IR and visible satellite data. The amplitude, temporal and spatial variability of these surface temperature anomalies depend primarily upon the storm size, storm intensity, translational velocity, and the underlying ocean conditions. Tropical cyclone 'cold wakes' are usually 2 - 5 °C cooler than pre-storm SSTs, and persist for days to weeks. Since storms that occur in rapid succession typically follow similar paths, the cold wake from one storm can affect development of subsequent storms. Recent studies, on both warm and cold wakes, have mostly focused on small subsets of global storms because of the amount of work it takes to co-locate different data sources to a storm's location. While a number of hurricane/typhoon websites exist that co-locate various datasets to TC locations, none provide 3-dimensional temporal and spatial structure of the ocean-atmosphere necessary to study cold/warm wake development and impact. We are developing a global 3-dimensional storm centric database for TC research. The database we propose will include in situ data, satellite data, and model analyses. Remote Sensing Systems (RSS) has a widely-used storm watch archive which provides the user an interface for visually analyzing collocated NASA Quick Scatterometer (QuikSCAT) winds with GHRSST microwave SSTs and SSM/I, TMI or AMSR-E rain rates for all global tropical cyclones 1999-2009. We will build on this concept of bringing together different data near storm locations when developing the storm-centric database. This database will be made available to researchers via the web display tools previously developed for RSS web pages. The database will provide scientists with a single data format collection of various atmospheric and oceanographic data, and will include all tropical storms since 1998, when the passive MW SSTs from the TMI instrument first became available. Initial results showing an analysis of Typhoon Man-Yi will be presented.

Man/computer communication in a space environment

NASA Technical Reports Server (NTRS)

Hodges, B. C.; Montoya, G.

1973-01-01

The present work reports on a study of the technology required to advance the state of the art in man/machine communications. The study involved the development and demonstration of both hardware and software to effectively implement man/computer interactive channels of communication. While tactile and visual man/computer communications equipment are standard methods of interaction with machines, man's speech is a natural media for inquiry and control. As part of this study, a word recognition unit was developed capable of recognizing a minimum of one hundred different words or sentences in any one of the currently used conversational languages. The study has proven that efficiency in communication between man and computer can be achieved when the vocabulary to be used is structured in a manner compatible with the rigid communication requirements of the machine while at the same time responsive to the informational needs of the man.

Homeopathy for attention deficit/hyperactivity disorder or hyperkinetic disorder.

PubMed

Coulter, M K; Dean, M E

2007-10-17

Homeopathy is one form of complementary/alternative medicine which is promoted as being a safe and effective form of treatment for children and adults. Within the UK homeopathy use is estimated at 1.9% of the adult population (Thomas 2004), and around 11% for children under 16 years (Simpson 2001). There has been increased interest in homeopathy's potential as a non-pharmacological intervention for attention deficit/hyperactivity disorder as an alternative to the use of stimulant medications such as Ritalin. Homeopathy is a system of medicine based on the principle of treating "like with like" using various dilutions of natural or man-made substances. Homeopathy focuses on the unique characteristics of each patient's experience and symptomatology and uses this information to determine the appropriate prescription for each patient. To assess the safety and effectiveness of homeopathy as a treatment for attention deficit/hyperactivity disorder. We searched a wide set of databases from their inception to March 2006 including: CENTRAL, MEDLINE, AMED, BIOSIS, CISCOM, CINAHL, Dissertation Abstracts, ECH (European Committee for Homeopathy thesis database), EMBASE, ERIC, HomInform (Glasgow Homeopathic Hospital Library), LILACS, PsycINFO, Science Citation Index, SIGLE, GIRI - International congress on ultra-low doses, Liga Medicorum Homeopathica Internationalis. We contacted experts in the field about ongoing or current research. All studies where individualised, clinical or formula homeopathy had been used to treat participants with ADHD or HKD who were randomly or quasi-randomly allocated to either true treatment or a control were selected. Control groups could include wait-list, no treatment, medication, placebo homeopathy, educational or behavioural interventions. Data from four eligible studies (total n = 168) were extracted and entered into RevMan. Results were synthesised and estimates of the effect sizes were calculated and presented as appropriate (using standardised mean differences) in both graphical and narrative form (narrative only was used where no effect size calculation was possible). The forms of homeopathy evaluated to date do not suggest significant treatment effects for the global symptoms, core symptoms of inattention, hyperactivity or impulsivity, or related outcomes such as anxiety in Attention Deficit/Hyperactivity Disorder. There is currently little evidence for the efficacy of homeopathy for the treatment of ADHD. Development of optimal treatment protocols is recommended prior to further randomised controlled trials being undertaken.

33 CFR 146.120 - Manning of survival craft.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Manning of survival craft. 146.120 Section 146.120 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES OPERATIONS Manned OCS Facilities § 146.120 Manning of survival craft. The owner, the owner's agent, or the...

Editorial Research Reports on Modern Man.

ERIC Educational Resources Information Center

Dickinson, William B., Jr., Ed.

Nine reports published in this volume study the uneasy coexistence of modern man and the complex society he has wrought. Man's apparent disorganized behavior is attributed to his inability to adapt readily to the charged pace of technological change. To combat the advancement of machine over man, he must, therefore, insist that moral and…

46 CFR 97.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Muster lists, emergency signals, and manning. 97.13-1... VESSELS OPERATIONS Station Bills § 97.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving...

46 CFR 78.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 3 2013-10-01 2013-10-01 false Muster lists, emergency signals, and manning. 78.13-1... OPERATIONS Station Bills § 78.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving Appliances and...

46 CFR 78.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 3 2014-10-01 2014-10-01 false Muster lists, emergency signals, and manning. 78.13-1... OPERATIONS Station Bills § 78.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving Appliances and...

42 CFR 84.102 - Man test 6; requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Man test 6; requirements. 84.102 Section 84.102 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND... Breathing Apparatus § 84.102 Man test 6; requirements. (a) Man test 6 will be conducted with respect to...

46 CFR 97.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Muster lists, emergency signals, and manning. 97.13-1... VESSELS OPERATIONS Station Bills § 97.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving...

42 CFR 84.102 - Man test 6; requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Man test 6; requirements. 84.102 Section 84.102 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND... Breathing Apparatus § 84.102 Man test 6; requirements. (a) Man test 6 will be conducted with respect to...

46 CFR 78.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 3 2012-10-01 2012-10-01 false Muster lists, emergency signals, and manning. 78.13-1... OPERATIONS Station Bills § 78.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving Appliances and...

46 CFR 97.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Muster lists, emergency signals, and manning. 97.13-1... VESSELS OPERATIONS Station Bills § 97.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving...

42 CFR 84.103 - Man tests; performance requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Man tests; performance requirements. 84.103 Section...-Contained Breathing Apparatus § 84.103 Man tests; performance requirements. (a) The apparatus shall satisfy... is 24 ±6 °C. (75 ±10 °F.), the maximum temperature of inspired air recorded during man tests shall...

42 CFR 84.102 - Man test 6; requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Man test 6; requirements. 84.102 Section 84.102 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND... Breathing Apparatus § 84.102 Man test 6; requirements. (a) Man test 6 will be conducted with respect to...

29 CFR 780.309 - Man-day exclusion.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 3 2014-07-01 2014-07-01 false Man-day exclusion. 780.309 Section 780.309 Labor...) Statutory Provisions § 780.309 Man-day exclusion. Section 3(e)(1) specifically excludes from the employer's man-day total (as defined in section 3(u)) employees who qualify for exemption under section 13(a)(6...

46 CFR 196.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Muster lists, emergency signals, and manning. 196.13-1... VESSELS OPERATIONS Station Bills § 196.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving...

29 CFR 780.317 - Man-day exclusion.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false Man-day exclusion. 780.317 Section 780.317 Labor...) Statutory Provisions § 780.317 Man-day exclusion. Section 3(e)(2) specifically excludes from the employer's man-day total (as defined in section 3(u)) employees who qualify for exemption under section 13(a)(6...

29 CFR 780.317 - Man-day exclusion.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 3 2014-07-01 2014-07-01 false Man-day exclusion. 780.317 Section 780.317 Labor...) Statutory Provisions § 780.317 Man-day exclusion. Section 3(e)(2) specifically excludes from the employer's man-day total (as defined in section 3(u)) employees who qualify for exemption under section 13(a)(6...

46 CFR 196.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Muster lists, emergency signals, and manning. 196.13-1... VESSELS OPERATIONS Station Bills § 196.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving...

29 CFR 780.317 - Man-day exclusion.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 3 2013-07-01 2013-07-01 false Man-day exclusion. 780.317 Section 780.317 Labor...) Statutory Provisions § 780.317 Man-day exclusion. Section 3(e)(2) specifically excludes from the employer's man-day total (as defined in section 3(u)) employees who qualify for exemption under section 13(a)(6...

42 CFR 84.102 - Man test 6; requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Man test 6; requirements. 84.102 Section 84.102 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND... Breathing Apparatus § 84.102 Man test 6; requirements. (a) Man test 6 will be conducted with respect to...

29 CFR 780.309 - Man-day exclusion.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 3 2013-07-01 2013-07-01 false Man-day exclusion. 780.309 Section 780.309 Labor...) Statutory Provisions § 780.309 Man-day exclusion. Section 3(e)(1) specifically excludes from the employer's man-day total (as defined in section 3(u)) employees who qualify for exemption under section 13(a)(6...

46 CFR 78.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 3 2011-10-01 2011-10-01 false Muster lists, emergency signals, and manning. 78.13-1... OPERATIONS Station Bills § 78.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving Appliances and...

46 CFR 196.13-1 - Muster lists, emergency signals, and manning.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Muster lists, emergency signals, and manning. 196.13-1... VESSELS OPERATIONS Station Bills § 196.13-1 Muster lists, emergency signals, and manning. The requirements for muster lists, emergency signals, and manning must be in accordance with subchapter W (Lifesaving...