Sample records for identified previously unknown

  1. Previously unknown species of Aspergillus.

    PubMed

    Gautier, M; Normand, A-C; Ranque, S

    2016-08-01

    The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care. Copyright © 2016 European Society of Clinical Microbiology and

  2. Twelve previously unknown phage genera are ubiquitous in global oceans

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

    Holmfeldt, Karin; Solonenko, Natalie; Shah, Manesh B

    Viruses are fundamental to ecosystems ranging from oceans to humans, yet our ability to study them is bottlenecked by the lack of ecologically relevant isolates, resulting in unknowns dominating culture-independent surveys. Here we present genomes from 31 phages infecting multiple strains of the aquatic bacterium Cellulophaga baltica (Bacteroidetes) to provide data for an underrepresented and environmentally abundant bacterial lineage. Comparative genomics delineated 12 phage groups that (i) each represent a new genus, and (ii) represent one novel and four wellknown viral families. This diversity contrasts the few well-studied marine phage systems, but parallels the diversity of phages infecting human-associated bacteria.more » Although all 12 Cellulophaga phages represent new genera, the podoviruses and icosahedral, nontailed ssDNA phages were exceptional, with genomes up to twice as large as those previously observed for each phage type. Structural novelty was also substantial, requiring experimental phage proteomics to identify 83% of the structural proteins. The presence of uncommon nucleotide metabolism genes in four genera likely underscores the importance of scavenging nutrient-rich molecules as previously seen for phages in marine environments. Metagenomic recruitment analyses suggest that these particular Cellulophaga phages are rare and may represent a first glimpse into the phage side of the rare biosphere. However, these analyses also revealed that these phage genera are widespread, occurring in 94% of 137 investigated metagenomes. Together, this diverse and novel collection of phages identifies a small but ubiquitous fraction of unknown marine viral diversity and provides numerous environmentally relevant phage host systems for experimental hypothesis testing.« less

  3. Twelve previously unknown phage genera are ubiquitous in global oceans.

    PubMed

    Holmfeldt, Karin; Solonenko, Natalie; Shah, Manesh; Corrier, Kristen; Riemann, Lasse; Verberkmoes, Nathan C; Sullivan, Matthew B

    2013-07-30

    Viruses are fundamental to ecosystems ranging from oceans to humans, yet our ability to study them is bottlenecked by the lack of ecologically relevant isolates, resulting in "unknowns" dominating culture-independent surveys. Here we present genomes from 31 phages infecting multiple strains of the aquatic bacterium Cellulophaga baltica (Bacteroidetes) to provide data for an underrepresented and environmentally abundant bacterial lineage. Comparative genomics delineated 12 phage groups that (i) each represent a new genus, and (ii) represent one novel and four well-known viral families. This diversity contrasts the few well-studied marine phage systems, but parallels the diversity of phages infecting human-associated bacteria. Although all 12 Cellulophaga phages represent new genera, the podoviruses and icosahedral, nontailed ssDNA phages were exceptional, with genomes up to twice as large as those previously observed for each phage type. Structural novelty was also substantial, requiring experimental phage proteomics to identify 83% of the structural proteins. The presence of uncommon nucleotide metabolism genes in four genera likely underscores the importance of scavenging nutrient-rich molecules as previously seen for phages in marine environments. Metagenomic recruitment analyses suggest that these particular Cellulophaga phages are rare and may represent a first glimpse into the phage side of the rare biosphere. However, these analyses also revealed that these phage genera are widespread, occurring in 94% of 137 investigated metagenomes. Together, this diverse and novel collection of phages identifies a small but ubiquitous fraction of unknown marine viral diversity and provides numerous environmentally relevant phage-host systems for experimental hypothesis testing.

  4. Identifying known unknowns using the US EPA's CompTox ...

    EPA Pesticide Factsheets

    Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most likely candidate “known unknowns,” which are those chemicals unknown to an investigator but contained within a reference database or literature source, rise to the top of a chemical list when rank-ordered by the number of associated data sources. The U.S. EPA’s CompTox Chemistry Dashboard is a curated and freely available resource for chemistry and computational toxicology research, containing more than 720,000 chemicals of relevance to environmental health science. In this research, the performance of the Dashboard for identifying “known unknowns” was evaluated against that of the online ChemSpider database, one of the primary resources used by mass spectrometrists, using multiple previously studied datasets reported in the peer-reviewed literature totaling 162 chemicals. These chemicals were examined using both applications via molecular formula and monoisotopic mass searches followed by rank-ordering of candidate compounds by associated references or data sources. A greater percentage of chemicals ranked in the top position when using the Dashboard, indicating an advantage of this application over ChemSpider for identifying known unknowns using data source ranking. Addition

  5. Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard.

    PubMed

    McEachran, Andrew D; Sobus, Jon R; Williams, Antony J

    2017-03-01

    Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most likely candidate "known unknowns," which are those chemicals unknown to an investigator but contained within a reference database or literature source, rise to the top of a chemical list when rank-ordered by the number of associated data sources. The U.S. EPA's CompTox Chemistry Dashboard is a curated and freely available resource for chemistry and computational toxicology research, containing more than 720,000 chemicals of relevance to environmental health science. In this research, the performance of the Dashboard for identifying known unknowns was evaluated against that of the online ChemSpider database, one of the primary resources used by mass spectrometrists, using multiple previously studied datasets reported in the peer-reviewed literature totaling 162 chemicals. These chemicals were examined using both applications via molecular formula and monoisotopic mass searches followed by rank-ordering of candidate compounds by associated references or data sources. A greater percentage of chemicals ranked in the top position when using the Dashboard, indicating an advantage of this application over ChemSpider for identifying known unknowns using data source ranking. Additional approaches are being developed for inclusion into a non-targeted analysis workflow as part of the CompTox Chemistry Dashboard. This work shows the potential for use of the Dashboard in exposure assessment and risk decision-making through significant improvements in non-targeted chemical identification. Graphical abstract Identifying known unknowns in the US EPA's CompTox Chemistry Dashboard from molecular formula and monoisotopic mass inputs.

  6. Using an epiphytic moss to identify previously unknown sources of atmospheric cadmium pollution

    Treesearch

    Geoffrey H. Donovan; Sarah E. Jovan; Demetrios Gatziolis; Igor Burstyn; Yvonne L. Michael; Michael C. Amacher; Vicente J. Monleon

    2016-01-01

    Urban networks of air-quality monitors are often too widely spaced to identify sources of air pollutants, especially if they do not disperse far from emission sources. The objectives of this study were to test the use of moss bio-indicators to develop a fine-scale map of atmospherically-derived cadmium and to identify the sources of cadmium in a complex urban setting....

  7. Previously unknown class of metalorganic compounds revealed in meteorites

    PubMed Central

    Ruf, Alexander; Kanawati, Basem; Hertkorn, Norbert; Yin, Qing-Zhu; Moritz, Franco; Harir, Mourad; Lucio, Marianna; Michalke, Bernhard; Wimpenny, Joshua; Shilobreeva, Svetlana; Bronsky, Basil; Saraykin, Vladimir; Gabelica, Zelimir; Gougeon, Régis D.; Quirico, Eric; Ralew, Stefan; Jakubowski, Tomasz; Haack, Henning; Gonsior, Michael; Jenniskens, Peter; Hinman, Nancy W.; Schmitt-Kopplin, Philippe

    2017-01-01

    The rich diversity and complexity of organic matter found in meteorites is rapidly expanding our knowledge and understanding of extreme environments from which the early solar system emerged and evolved. Here, we report the discovery of a hitherto unknown chemical class, dihydroxymagnesium carboxylates [(OH)2MgO2CR]−, in meteoritic soluble organic matter. High collision energies, which are required for fragmentation, suggest substantial thermal stability of these Mg-metalorganics (CHOMg compounds). This was corroborated by their higher abundance in thermally processed meteorites. CHOMg compounds were found to be present in a set of 61 meteorites of diverse petrological classes. The appearance of this CHOMg chemical class extends the previously investigated, diverse set of CHNOS molecules. A connection between the evolution of organic compounds and minerals is made, as Mg released from minerals gets trapped into organic compounds. These CHOMg metalorganic compounds and their relation to thermal processing in meteorites might shed new light on our understanding of carbon speciation at a molecular level in meteorite parent bodies. PMID:28242686

  8. Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis

    PubMed Central

    Chakrabarti, Kausik; Pearson, Michael; Grate, Leslie; Sterne-Weiler, Timothy; Deans, Jonathan; Donohue, John Paul; Ares, Manuel

    2007-01-01

    As the genomes of more eukaryotic pathogens are sequenced, understanding how molecular differences between parasite and host might be exploited to provide new therapies has become a major focus. Central to cell function are RNA-containing complexes involved in gene expression, such as the ribosome, the spliceosome, snoRNAs, RNase P, and telomerase, among others. In this article we identify by comparative genomics and validate by RNA analysis numerous previously unknown structural RNAs encoded by the Plasmodium falciparum genome, including the telomerase RNA, U3, 31 snoRNAs, as well as previously predicted spliceosomal snRNAs, SRP RNA, MRP RNA, and RNAse P RNA. Furthermore, we identify six new RNA coding genes of unknown function. To investigate the relationships of the RNA coding genes to other genomic features in related parasites, we developed a genome browser for P. falciparum (http://areslab.ucsc.edu/cgi-bin/hgGateway). Additional experiments provide evidence supporting the prediction that snoRNAs guide methylation of a specific position on U4 snRNA, as well as predicting an snRNA promoter element particular to Plasmodium sp. These findings should allow detailed structural comparisons between the RNA components of the gene expression machinery of the parasite and its vertebrate hosts. PMID:17901154

  9. Identification and characterisation of a previously unknown drought tolerance-associated microRNA in barley.

    PubMed

    Zhou, Hui; Hussain, Syed Sarfraz; Hackenberg, Michael; Bazanova, Natalia; Eini, Omid; Li, Jie; Gustafson, Perry; Shi, Bujun

    2018-04-22

    Drought is the most serious abiotic stress, which causes crop losses on worldwide scale. The present study identified a previously unknown microRNA (designated as hvu-miRX) of 21 nucleotides (nt) in barley. Its precursor (designated pre-miRX) and primary transcript (designated pri-miRX) were also identified, with lengths of 73 nt and 559 nt, respectively. The identified upstream sequence of pri-miRX contains both the TATA box and the CAAT box, which are both required for transcription initiation. Transient promoter activation assays showed that the core promoter region of pri-miRX ranged 500 nt from the transcription start site. In transgenic barley over-expressing the wheat DREB3 transcription factor (TaDREB3) caused hvu-miRX to be highly expressed as compared to the same miRNA in non-transgenic barley. However, the high expression was not directly associated with TaDREB3. Genomic analysis revealed that the hvu-miRX gene was a single copy located on the short arm of chromosome 2 and appeared to be only conserved in Triticeae, but not in other plant species. Notably, transgenic barley overexpressing hvu-miRX showed drought tolerance. Degradome library analysis and other tests showed that hvu-miRX targeted various genes including transcription factors via the cleavage mode. Our data open an excellent opportunity to develop drought stress tolerant cereals with hvu-miRX. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Using an epiphytic moss to identify previously unknown sources of atmospheric cadmium pollution.

    PubMed

    Donovan, Geoffrey H; Jovan, Sarah E; Gatziolis, Demetrios; Burstyn, Igor; Michael, Yvonne L; Amacher, Michael C; Monleon, Vicente J

    2016-07-15

    Urban networks of air-quality monitors are often too widely spaced to identify sources of air pollutants, especially if they do not disperse far from emission sources. The objectives of this study were to test the use of moss bio-indicators to develop a fine-scale map of atmospherically-derived cadmium and to identify the sources of cadmium in a complex urban setting. We collected 346 samples of the moss Orthotrichum lyellii from deciduous trees in December, 2013 using a modified randomized grid-based sampling strategy across Portland, Oregon. We estimated a spatial linear model of moss cadmium levels and predicted cadmium on a 50m grid across the city. Cadmium levels in moss were positively correlated with proximity to two stained-glass manufacturers, proximity to the Oregon-Washington border, and percent industrial land in a 500m buffer, and negatively correlated with percent residential land in a 500m buffer. The maps showed very high concentrations of cadmium around the two stained-glass manufacturers, neither of which were known to environmental regulators as cadmium emitters. In addition, in response to our findings, the Oregon Department of Environmental Quality placed an instrumental monitor 120m from the larger stained-glass manufacturer in October, 2015. The monthly average atmospheric cadmium concentration was 29.4ng/m(3), which is 49 times higher than Oregon's benchmark of 0.6ng/m(3), and high enough to pose a health risk from even short-term exposure. Both stained-glass manufacturers voluntarily stopped using cadmium after the monitoring results were made public, and the monthly average cadmium levels precipitously dropped to 1.1ng/m(3) for stained-glass manufacturer #1 and 0.67ng/m(3) for stained-glass manufacturer #2. Published by Elsevier B.V.

  11. Allocating monitoring effort in the face of unknown unknowns

    USGS Publications Warehouse

    Wintle, B.A.; Runge, M.C.; Bekessy, S.A.

    2010-01-01

    There is a growing view that to make efficient use of resources, ecological monitoring should be hypothesis-driven and targeted to address specific management questions. 'Targeted' monitoring has been contrasted with other approaches in which a range of quantities are monitored in case they exhibit an alarming trend or provide ad hoc ecological insights. The second form of monitoring, described as surveillance, has been criticized because it does not usually aim to discern between competing hypotheses, and its benefits are harder to identify a priori. The alternative view is that the existence of surveillance data may enable rapid corroboration of emerging hypotheses or help to detect important 'unknown unknowns' that, if undetected, could lead to catastrophic outcomes or missed opportunities. We derive a model to evaluate and compare the efficiency of investments in surveillance and targeted monitoring. We find that a decision to invest in surveillance monitoring may be defensible if: (1) the surveillance design is more likely to discover or corroborate previously unknown phenomena than a targeted design and (2) the expected benefits (or avoided costs) arising from discovery are substantially higher than those arising from a well-planned targeted design. Our examination highlights the importance of being explicit about the objectives, costs and expected benefits of monitoring in a decision analytic framework. ?? 2010 Blackwell Publishing Ltd/CNRS.

  12. Searching for 'Unknown Unknowns'

    NASA Technical Reports Server (NTRS)

    Parsons, Vickie S.

    2005-01-01

    The NASA Engineering and Safety Center (NESC) was established to improve safety through engineering excellence within NASA programs and projects. As part of this goal, methods are being investigated to enable the NESC to become proactive in identifying areas that may be precursors to future problems. The goal is to find unknown indicators of future problems, not to duplicate the program-specific trending efforts. The data that is critical for detecting these indicators exist in a plethora of dissimilar non-conformance and other databases (without a common format or taxonomy). In fact, much of the data is unstructured text. However, one common database is not required if the right standards and electronic tools are employed. Electronic data mining is a particularly promising tool for this effort into unsupervised learning of common factors. This work in progress began with a systematic evaluation of available data mining software packages, based on documented decision techniques using weighted criteria. The four packages, which were perceived to have the most promise for NASA applications, are being benchmarked and evaluated by independent contractors. Preliminary recommendations for "best practices" in data mining and trending are provided. Final results and recommendations should be available in the Fall 2005. This critical first step in identifying "unknown unknowns" before they become problems is applicable to any set of engineering or programmatic data.

  13. Method for identifying known materials within a mixture of unknowns

    DOEpatents

    Wagner, John S.

    2000-01-01

    One or both of two methods and systems are used to determine concentration of a known material in an unknown mixture on the basis of the measured interaction of electromagnetic waves upon the mixture. One technique is to utilize a multivariate analysis patch technique to develop a library of optimized patches of spectral signatures of known materials containing only those pixels most descriptive of the known materials by an evolutionary algorithm. Identity and concentration of the known materials within the unknown mixture is then determined by minimizing the residuals between the measurements from the library of optimized patches and the measurements from the same pixels from the unknown mixture. Another technique is to train a neural network by the genetic algorithm to determine the identity and concentration of known materials in the unknown mixture. The two techniques may be combined into an expert system providing cross checks for accuracy.

  14. System for identifying known materials within a mixture of unknowns

    DOEpatents

    Wagner, John S.

    1999-01-01

    One or both of two methods and systems are used to determine concentration of a known material in an unknown mixture on the basis of the measured interaction of electromagnetic waves upon the mixture. One technique is to utilize a multivariate analysis patch technique to develop a library of optimized patches of spectral signatures of known materials containing only those pixels most descriptive of the known materials by an evolutionary algorithm. Identity and concentration of the known materials within the unknown mixture is then determined by minimizing the residuals between the measurements from the library of optimized patches and the measurements from the same pixels from the unknown mixture. Another technique is to train a neural network by the genetic algorithm to determine the identity and concentration of known materials in the unknown mixture. The two techniques may be combined into an expert system providing cross checks for accuracy.

  15. System for identifying known materials within a mixture of unknowns

    DOEpatents

    Wagner, J.S.

    1999-07-20

    One or both of two methods and systems are used to determine concentration of a known material in an unknown mixture on the basis of the measured interaction of electromagnetic waves upon the mixture. One technique is to utilize a multivariate analysis patch technique to develop a library of optimized patches of spectral signatures of known materials containing only those pixels most descriptive of the known materials by an evolutionary algorithm. Identity and concentration of the known materials within the unknown mixture is then determined by minimizing the residuals between the measurements from the library of optimized patches and the measurements from the same pixels from the unknown mixture. Another technique is to train a neural network by the genetic algorithm to determine the identity and concentration of known materials in the unknown mixture. The two techniques may be combined into an expert system providing cross checks for accuracy. 37 figs.

  16. Chitin-Like Molecules Associate with Cryptococcus neoformans Glucuronoxylomannan To Form a Glycan Complex with Previously Unknown Properties

    PubMed Central

    Ramos, Caroline L.; Fonseca, Fernanda L.; Rodrigues, Jessica; Guimarães, Allan J.; Cinelli, Leonardo P.; Miranda, Kildare; Nimrichter, Leonardo; Casadevall, Arturo; Travassos, Luiz R.

    2012-01-01

    In prior studies, we demonstrated that glucuronoxylomannan (GXM), the major capsular polysaccharide of the fungal pathogen Cryptococcus neoformans, interacts with chitin oligomers at the cell wall-capsule interface. The structural determinants regulating these carbohydrate-carbohydrate interactions, as well as the functions of these structures, have remained unknown. In this study, we demonstrate that glycan complexes composed of chitooligomers and GXM are formed during fungal growth and macrophage infection by C. neoformans. To investigate the required determinants for the assembly of chitin-GXM complexes, we developed a quantitative scanning electron microscopy-based method using different polysaccharide samples as inhibitors of the interaction of chitin with GXM. This assay revealed that chitin-GXM association involves noncovalent bonds and large GXM fibers and depends on the N-acetyl amino group of chitin. Carboxyl and O-acetyl groups of GXM are not required for polysaccharide-polysaccharide interactions. Glycan complex structures composed of cryptococcal GXM and chitin-derived oligomers were tested for their ability to induce pulmonary cytokines in mice. They were significantly more efficient than either GXM or chitin oligomers alone in inducing the production of lung interleukin 10 (IL-10), IL-17, and tumor necrosis factor alpha (TNF-α). These results indicate that association of chitin-derived structures with GXM through their N-acetyl amino groups generates glycan complexes with previously unknown properties. PMID:22562469

  17. NIH Researchers Identify OCD Risk Gene

    MedlinePlus

    ... News From NIH NIH Researchers Identify OCD Risk Gene Past Issues / Summer 2006 Table of Contents For ... and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual's risk for obsessive- ...

  18. Identification of Balanced Chromosomal Rearrangements Previously Unknown Among Participants in the 1000 Genomes Project: Implications for Interpretation of Structural Variation in Genomes and the Future of Clinical Cytogenetics

    PubMed Central

    Dong, Zirui; Wang, Huilin; Chen, Haixiao; Jiang, Hui; Yuan, Jianying; Yang, Zhenjun; Wang, Wen-Jing; Xu, Fengping; Guo, Xiaosen; Cao, Ye; Zhu, Zhenzhen; Geng, Chunyu; Cheung, Wan Chee; Kwok, Yvonne K; Yang, Huangming; Leung, Tak Yeung; Morton, Cynthia C.; Cheung, Sau Wai; Choy, Kwong Wai

    2017-01-01

    Purpose Recent studies demonstrate that whole-genome sequencing (WGS) enables detection of cryptic rearrangements in apparently balanced chromosomal rearrangements (also known as balanced chromosomal abnormalities, BCAs) previously identified by conventional cytogenetic methods. We aimed to assess our analytical tool for detecting BCAs in The 1000 Genomes Project without knowing affected bands. Methods The 1000 Genomes Project provides an unprecedented integrated map of structural variants in phenotypically normal subjects, but there is no information on potential inclusion of subjects with apparently BCAs akin to those traditionally detected in diagnostic cytogenetics laboratories. We applied our analytical tool to 1,166 genomes from the 1000 Genomes Project with sufficient physical coverage (8.25-fold). Results Our approach detected four reciprocal balanced translocations and four inversions ranging in size from 57.9 kb to 13.3 Mb, all of which were confirmed by cytogenetic methods and PCR studies. One of DNAs has a subtle translocation that is not readily identified by chromosome analysis due to similar banding patterns and size of exchanged segments, and another results in disruption of all transcripts of an OMIM gene. Conclusions Our study demonstrates the extension of utilizing low-coverage WGS for unbiased detection of BCAs including translocations and inversions previously unknown in the 1000 Genomes Project. PMID:29095815

  19. Validation of social skills of adolescent males in an interview conversation with a previously unknown adult.

    PubMed

    Spence, S H

    1981-01-01

    Seventy convicted young male offenders were videotaped during a 5-min standardized interview with a previously unknown adult. In order to determine the social validity of the behavioral components of social interaction for this population, measures of 13 behaviors were obtained from the tapes. These measures were then correlated with ratings of friendliness, social anxiety, social skills performance, and employability made by four independent adult judges from the same tapes. It was found that measures of eye contact and verbal initiations were correlated significantly with all four criterion rating scales. The frequencies of smiling and speech dysfluencies were both significantly correlated with ratings of friendliness and employability. The amount spoken was found to be a significant predictor of social skills performance whereas the frequency of head movements influenced judgments of social anxiety. The latency of response was negatively correlated with social skills and employability ratings and the frequency of question-asking and interruptions correlated significantly with friendliness, social skills, and employability ratings. Finally, the levels of gestures, gross body movements, and attention feedback responses were not found to influence judgments on any of the criterion scales. The implications of the study for selection of targets for social skills training for adolescent male offenders are discussed.

  20. Validation of social skills of adolescent males in an interview conversation with a previously unknown adult.

    PubMed Central

    Spence, S H

    1981-01-01

    Seventy convicted young male offenders were videotaped during a 5-min standardized interview with a previously unknown adult. In order to determine the social validity of the behavioral components of social interaction for this population, measures of 13 behaviors were obtained from the tapes. These measures were then correlated with ratings of friendliness, social anxiety, social skills performance, and employability made by four independent adult judges from the same tapes. It was found that measures of eye contact and verbal initiations were correlated significantly with all four criterion rating scales. The frequencies of smiling and speech dysfluencies were both significantly correlated with ratings of friendliness and employability. The amount spoken was found to be a significant predictor of social skills performance whereas the frequency of head movements influenced judgments of social anxiety. The latency of response was negatively correlated with social skills and employability ratings and the frequency of question-asking and interruptions correlated significantly with friendliness, social skills, and employability ratings. Finally, the levels of gestures, gross body movements, and attention feedback responses were not found to influence judgments on any of the criterion scales. The implications of the study for selection of targets for social skills training for adolescent male offenders are discussed. PMID:7287599

  1. Monoterpene Unknowns Identified Using IR, [to the first power]H-NMR, [to the thirteenth power]C-NMR, DEPT, COSY, and HETCOR

    ERIC Educational Resources Information Center

    Alty, Lisa T.

    2005-01-01

    A study identifies a compound from a set of monoterpenes using infrared (IR) and one-dimensional (1D) nuclear magnetic resonance (NMR) techniques. After identifying the unknown, each carbon and proton signal can be interpreted and assigned to the structure using the information in the two-dimensional (2D) NMR spectra, correlation spectroscopy…

  2. Preteaching Unknown Key Words with Incremental Rehearsal to Improve Reading Fluency and Comprehension with Children Identified as Reading Disabled

    ERIC Educational Resources Information Center

    Burns, Matthew K.; Dean, Vincent J.; Foley, Sarah

    2004-01-01

    Research has consistently demonstrated that strategic preteaching activities led to improved reading fluency, but lacked studies examining the effect on reading comprehension. The current study investigated the effect of teaching unknown key words as a preteaching strategy with 20 students identified as learning disabled in basic reading skills…

  3. Identification of balanced chromosomal rearrangements previously unknown among participants in the 1000 Genomes Project: implications for interpretation of structural variation in genomes and the future of clinical cytogenetics.

    PubMed

    Dong, Zirui; Wang, Huilin; Chen, Haixiao; Jiang, Hui; Yuan, Jianying; Yang, Zhenjun; Wang, Wen-Jing; Xu, Fengping; Guo, Xiaosen; Cao, Ye; Zhu, Zhenzhen; Geng, Chunyu; Cheung, Wan Chee; Kwok, Yvonne K; Yang, Huanming; Leung, Tak Yeung; Morton, Cynthia C; Cheung, Sau Wai; Choy, Kwong Wai

    2017-11-02

    PurposeRecent studies demonstrate that whole-genome sequencing enables detection of cryptic rearrangements in apparently balanced chromosomal rearrangements (also known as balanced chromosomal abnormalities, BCAs) previously identified by conventional cytogenetic methods. We aimed to assess our analytical tool for detecting BCAs in the 1000 Genomes Project without knowing which bands were affected.MethodsThe 1000 Genomes Project provides an unprecedented integrated map of structural variants in phenotypically normal subjects, but there is no information on potential inclusion of subjects with apparent BCAs akin to those traditionally detected in diagnostic cytogenetics laboratories. We applied our analytical tool to 1,166 genomes from the 1000 Genomes Project with sufficient physical coverage (8.25-fold).ResultsWith this approach, we detected four reciprocal balanced translocations and four inversions, ranging in size from 57.9 kb to 13.3 Mb, all of which were confirmed by cytogenetic methods and polymerase chain reaction studies. One of these DNAs has a subtle translocation that is not readily identified by chromosome analysis because of the similarity of the banding patterns and size of exchanged segments, and another results in disruption of all transcripts of an OMIM gene.ConclusionOur study demonstrates the extension of utilizing low-pass whole-genome sequencing for unbiased detection of BCAs including translocations and inversions previously unknown in the 1000 Genomes Project.GENETICS in MEDICINE advance online publication, 2 November 2017; doi:10.1038/gim.2017.170.

  4. Breeding sites and winter site fidelity of Piping Plovers wintering in The Bahamas, a previously unknown major wintering area

    USGS Publications Warehouse

    Gratto-Trevor, Cheri; Haig, Susan M.; Miller, Mark P.; Mullins, Thomas D.; Maddock, Sidney; Roche, Erin A.; Moore, Predensa

    2016-01-01

    Most of the known wintering areas of Piping Plovers (Charadrius melodus) are along the Atlantic and Gulf coasts of the United States and into Mexico, and in the Caribbean. However, 1066 threatened/endangered Piping Plovers were recently found wintering in The Bahamas, an area not previously known to be important for the species. Although representing about 27% of the birds counted during the 2011 International Piping Plover Winter Census, the location of their breeding site(s) was unknown. Thus, our objectives were to determine the location(s) of their breeding site(s) using molecular markers and by tracking banded individuals, identify spring and fall staging sites, and examine site fidelity and survival. We captured and color-banded 57 birds in January and February 2010 in The Bahamas. Blood samples were also collected for genetic evaluation of the likely subspecies wintering in The Bahamas. Band re-sightings and DNA analysis revealed that at least 95% of the Piping Plovers wintering in The Bahamas originated on the Atlantic coast of the United States and Canada. Re-sightings of birds banded in The Bahamas spanned the breeding distribution of the species along the Atlantic coast from Newfoundland to North Carolina. Site fidelity to breeding and wintering sites was high (88–100%). Spring and fall staging sites were located along the Atlantic coast of the United States, with marked birds concentrating in the Carolinas. Our estimate of true survival for the marked birds was 0.71 (95% CI: 0.61–0.80). Our results indicate that more than one third of the Piping Plover population that breeds along the Atlantic coast winters in The Bahamas. By determining the importance of The Bahamas to the Atlantic subspecies of Piping Plovers, future conservation efforts for these populations can be better focused on where they are most needed.

  5. Previously unknown and highly divergent ssDNA viruses populate the oceans.

    PubMed

    Labonté, Jessica M; Suttle, Curtis A

    2013-11-01

    Single-stranded DNA (ssDNA) viruses are economically important pathogens of plants and animals, and are widespread in oceans; yet, the diversity and evolutionary relationships among marine ssDNA viruses remain largely unknown. Here we present the results from a metagenomic study of composite samples from temperate (Saanich Inlet, 11 samples; Strait of Georgia, 85 samples) and subtropical (46 samples, Gulf of Mexico) seawater. Most sequences (84%) had no evident similarity to sequenced viruses. In total, 608 putative complete genomes of ssDNA viruses were assembled, almost doubling the number of ssDNA viral genomes in databases. These comprised 129 genetically distinct groups, each represented by at least one complete genome that had no recognizable similarity to each other or to other virus sequences. Given that the seven recognized families of ssDNA viruses have considerable sequence homology within them, this suggests that many of these genetic groups may represent new viral families. Moreover, nearly 70% of the sequences were similar to one of these genomes, indicating that most of the sequences could be assigned to a genetically distinct group. Most sequences fell within 11 well-defined gene groups, each sharing a common gene. Some of these encoded putative replication and coat proteins that had similarity to sequences from viruses infecting eukaryotes, suggesting that these were likely from viruses infecting eukaryotic phytoplankton and zooplankton.

  6. Previously unknown apicomplexan species infecting Iceland scallop, Chlamys islandica (Müller, 1776), queen scallop, Aequipecten opercularis L., and king scallop, Pecten maximus L.

    PubMed

    Kristmundsson, Árni; Helgason, Sigurður; Bambir, Slavko Helgi; Eydal, Matthías; Freeman, Mark A

    2011-11-01

    Examination of three scallop species from three separate locations: Iceland scallop from Icelandic waters, king scallop from Scottish waters and queen scallop from Faroese and Scottish waters, revealed infections of a previously unknown apicomplexan parasite in all three scallop species. Developmental forms observed in the shells appeared to include both sexual and asexual stages of the parasite, i.e. merogony, gametogony and sporogony, which suggests a monoxenous life cycle. Meronts, gamonts, zygotes and mature oocysts were solely found in the muscular tissue. Zoites, which could be sporozoites and/or merozoites, were observed in great numbers, most frequently in muscles, both intracellular and free in the extracellular space. Zoites were also common inside haemocytes. Examination of the ultrastructure showed that the zoites contained all the major structures characterizing apicomplexans. This apicomplexan parasite is morphologically different from other apicomplexan species previously described from bivalves. Presently, its systematic position within the phylum Apicomplexa cannot be ascertained. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Preliminary assessment of a previously unknown fault zone beneath the Daytona Beach sand blow cluster near Marianna, Arkansas

    USGS Publications Warehouse

    Odum, Jackson K.; Williams, Robert; Stephenson, William J.; Tuttle, Martitia P.; Al-Shukri, Hadar

    2016-01-01

    We collected new high‐resolution P‐wave seismic‐reflection data to explore for possible faults beneath a roughly linear cluster of early to mid‐Holocene earthquake‐induced sand blows to the south of Marianna, Arkansas. The Daytona Beach sand blow deposits are located in east‐central Arkansas about 75 km southwest of Memphis, Tennessee, and about 80 km south of the southwestern end of the New Madrid seismic zone (NMSZ). Previous studies of these sand blows indicate that they were produced between 10,500 and 5350 yr B.P. (before A.D. 1950). The sand blows are large and similar in size to those in the heart of the NMSZ produced by the 1811–1812 earthquakes. The seismic‐reflection profiles reveal a previously unknown zone of near‐vertical faults imaged in the 100–1100‐m depth range that are approximately coincident with a cluster of earthquake‐induced sand blows and a near‐linear surface lineament composed of air photo tonal anomalies. These interpreted faults are expressed as vertical discontinuities with the largest displacement fault showing about 40 m of west‐side‐up displacement at the top of the Paleozoic section at about 1100 m depth. There are about 20 m of folding on reflections within the Eocene strata at 400 m depth. Increasing fault displacement with depth suggests long‐term recurrent faulting. The imaged faults within the vicinity of the numerous sand blow features could be a causative earthquake source, although it does not rule out the possibility of other seismic sources nearby. These newly located faults add to a growing list of potentially active Pleistocene–Holocene faults discovered over the last two decades that are within the Mississippi embayment region but outside of the historical NMSZ.

  8. Unknown beaked whale echolocation signals recorded off eastern New Zealand.

    PubMed

    Giorli, Giacomo; Goetz, Kimberly T; Delarue, Julien; Maxner, Emily; Kowarski, Katie A; Bruce Martin, Steven; McPherson, Craig

    2018-04-01

    The echolocation signals of most beaked whale species are still unknown. In fact, out of the 22 species comprising the family Ziphiidae, only the echolocation pulses for 7 species have been clearly described. This study describes two distinct beaked whale echolocation signals recorded in the Cook Strait region using passive acoustic technology. These signals differ from previously described Ziphiid species clicks. A description of the time-frequency characteristics of the two signals is provided. Understanding the characteristics of these signals is necessary to correctly identify species from their echolocation signals and enables future monitoring of beaked whales using passive acoustics techniques.

  9. Detecting Unknown Artificial Urban Surface Materials Based on Spectral Dissimilarity Analysis.

    PubMed

    Jilge, Marianne; Heiden, Uta; Habermeyer, Martin; Mende, André; Juergens, Carsten

    2017-08-08

    High resolution imaging spectroscopy data have been recognised as a valuable data resource for augmenting detailed material inventories that serve as input for various urban applications. Image-specific urban spectral libraries are successfully used in urban imaging spectroscopy studies. However, the regional- and sensor-specific transferability of such libraries is limited due to the wide range of different surface materials. With the developed methodology, incomplete urban spectral libraries can be utilised by assuming that unknown surface material spectra are dissimilar to the known spectra in a basic spectral library (BSL). The similarity measure SID-SCA (Spectral Information Divergence-Spectral Correlation Angle) is applied to detect image-specific unknown urban surfaces while avoiding spectral mixtures. These detected unknown materials are categorised into distinct and identifiable material classes based on their spectral and spatial metrics. Experimental results demonstrate a successful redetection of material classes that had been previously erased in order to simulate an incomplete BSL. Additionally, completely new materials e.g., solar panels were identified in the data. It is further shown that the level of incompleteness of the BSL and the defined dissimilarity threshold are decisive for the detection of unknown material classes and the degree of spectral intra-class variability. A detailed accuracy assessment of the pre-classification results, aiming to separate natural and artificial materials, demonstrates spectral confusions between spectrally similar materials utilizing SID-SCA. However, most spectral confusions occur between natural or artificial materials which are not affecting the overall aim. The dissimilarity analysis overcomes the limitations of working with incomplete urban spectral libraries and enables the generation of image-specific training databases.

  10. Detecting Unknown Artificial Urban Surface Materials Based on Spectral Dissimilarity Analysis

    PubMed Central

    Jilge, Marianne; Heiden, Uta; Habermeyer, Martin; Mende, André; Juergens, Carsten

    2017-01-01

    High resolution imaging spectroscopy data have been recognised as a valuable data resource for augmenting detailed material inventories that serve as input for various urban applications. Image-specific urban spectral libraries are successfully used in urban imaging spectroscopy studies. However, the regional- and sensor-specific transferability of such libraries is limited due to the wide range of different surface materials. With the developed methodology, incomplete urban spectral libraries can be utilised by assuming that unknown surface material spectra are dissimilar to the known spectra in a basic spectral library (BSL). The similarity measure SID-SCA (Spectral Information Divergence-Spectral Correlation Angle) is applied to detect image-specific unknown urban surfaces while avoiding spectral mixtures. These detected unknown materials are categorised into distinct and identifiable material classes based on their spectral and spatial metrics. Experimental results demonstrate a successful redetection of material classes that had been previously erased in order to simulate an incomplete BSL. Additionally, completely new materials e.g., solar panels were identified in the data. It is further shown that the level of incompleteness of the BSL and the defined dissimilarity threshold are decisive for the detection of unknown material classes and the degree of spectral intra-class variability. A detailed accuracy assessment of the pre-classification results, aiming to separate natural and artificial materials, demonstrates spectral confusions between spectrally similar materials utilizing SID-SCA. However, most spectral confusions occur between natural or artificial materials which are not affecting the overall aim. The dissimilarity analysis overcomes the limitations of working with incomplete urban spectral libraries and enables the generation of image-specific training databases. PMID:28786947

  11. Post-operative therapy following transoral robotic surgery for unknown primary cancers of the head and neck.

    PubMed

    Patel, Sapna A; Parvathaneni, Aarthi; Parvathaneni, Upendra; Houlton, Jeffrey J; Karni, Ron J; Liao, Jay J; Futran, Neal D; Méndez, Eduardo

    2017-09-01

    Our primary objective is to describe the post- operative management in patients with an unknown primary squamous cell carcinoma of the head and neck (HNSCC) treated with trans-oral robotic surgery (TORS). We conducted a retrospective multi-institutional case series including all patients diagnosed with an unknown primary HNSCC who underwent TORS to identify the primary site from January 1, 2010 to June 30, 2016. We excluded those with recurrent disease, ≤6months of follow up from TORS, previous history of radiation therapy (RT) to the head and neck, or evidence of primary tumor site based on previous biopsies. Our main outcome measure was receipt of post-operative therapy. The tumor was identified in 26/35 (74.3%) subjects. Post-TORS, 2 subjects did not receive adjuvant therapy due to favorable pathology. Volume reduction of RT mucosal site coverage was achieved in 12/26 (46.1%) subjects who had lateralizing tumors, ie. those confined to the palatine tonsil or glossotonsillar sulcus. In addition, for 8/26 (30.1%), the contralateral neck RT was also avoided. In 9 subjects, no primary was identified (pT0); four of these received RT to the involved ipsilateral neck nodal basin only without pharyngeal mucosal irradiation. Surgical management of an unknown primary with TORS can lead to deintensification of adjuvant therapy including avoidance of chemotherapy and reduction in RT doses and volume. There was no increase in short term treatment failures. Treatment after TORS can vary significantly, thus we advocate adherence to NCCN guideline therapy post-TORS to avoid treatment-associated variability. Published by Elsevier Ltd.

  12. [The changing spectrum of fever of unknown origin: trends and comparison with previous series at the Salvador Zubirán National Institute of Nutrition].

    PubMed

    Molina-Gamboa, J; Rivera-Morales, I; Camacho-Mezquita, E; Ponce-de-León, S

    1994-01-01

    We reviewed 400 medical records of patients admitted because of fever at the National Institute of Nutrition Salvador Zubirán between January 1, 1988 to December 31, 1992. Patient characteristics, diagnostic methods, final diagnosis and patient progress were analyzed, comparing these data with the previous series of the institute. We found 77 cases of fever of unknown origin (FUO), 47 males and 30 females, between 14 to 87 years of age. The final diagnosis encountered were: infections (40%), neoplasias (23%), collagen diseases (13%), and other diagnosis (8%). Sixteen percent of the cases remained without a final diagnosis. The most frequent infections were HIV infection (19%), tuberculosis (19%) and endocarditis (13%). The most common neoplasia was lymphoma (55.6%), with 90% of Hodgkin's disease. SLE was the most common autoimmune disease found. The methods to establish a final diagnosis were: biopsies (52%), serology (17%), cultures (12%), image (11%), and clinical (8%). Final diagnosis by serology tests increased from 2 to 17% in comparison with previous reports. Eight laparotomies were done, which is a less frequent practice than previously (10 vs 35%). We saw only one case of amebic hepatic abscess and had no cases of malaria and salmonellosis as final diagnosis of FUO; HIV infection was found to be a new major cause of FUO.

  13. Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions

    DOE PAGES

    Jiang, Jiansen; Chan, Henry; Cash, Darian D.; ...

    2015-10-15

    Telomerase helps maintain telomeres by processive synthesis of telomere repeat DNA at their 3'-ends, using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). In this paper, we report the cryo–electron microscopy structure of Tetrahymena telomerase at ~9 angstrom resolution. In addition to seven known holoenzyme proteins, we identify two additional proteins that form a complex (TEB) with single-stranded telomere DNA-binding protein Teb1, paralogous to heterotrimeric replication protein A (RPA). The p75-p45-p19 subcomplex is identified as another RPA-related complex, CST (CTC1-STN1-TEN1). This study reveals the paths of TER in the TERT-TER-p65 catalytic core and single-stranded DNA exit; extensive subunitmore » interactions of the TERT essential N-terminal domain, p50, and TEB; and other subunit identities and structures, including p19 and p45C crystal structures. Finally, our findings provide structural and mechanistic insights into telomerase holoenzyme function.« less

  14. Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions

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

    Jiang, Jiansen; Chan, Henry; Cash, Darian D.

    Telomerase helps maintain telomeres by processive synthesis of telomere repeat DNA at their 3'-ends, using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). In this paper, we report the cryo–electron microscopy structure of Tetrahymena telomerase at ~9 angstrom resolution. In addition to seven known holoenzyme proteins, we identify two additional proteins that form a complex (TEB) with single-stranded telomere DNA-binding protein Teb1, paralogous to heterotrimeric replication protein A (RPA). The p75-p45-p19 subcomplex is identified as another RPA-related complex, CST (CTC1-STN1-TEN1). This study reveals the paths of TER in the TERT-TER-p65 catalytic core and single-stranded DNA exit; extensive subunitmore » interactions of the TERT essential N-terminal domain, p50, and TEB; and other subunit identities and structures, including p19 and p45C crystal structures. Finally, our findings provide structural and mechanistic insights into telomerase holoenzyme function.« less

  15. 5 CFR 1651.16 - Missing and unknown beneficiaries.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Missing and unknown beneficiaries. 1651... § 1651.16 Missing and unknown beneficiaries. (a) Locate and identify beneficiaries. (1) The TSP record... one or more beneficiaries (and not all) appear to be missing, payment of part of the participant's...

  16. 5 CFR 1651.16 - Missing and unknown beneficiaries.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Missing and unknown beneficiaries. 1651... § 1651.16 Missing and unknown beneficiaries. (a) Locate and identify beneficiaries. (1) The TSP record... one or more beneficiaries (and not all) appear to be missing, payment of part of the participant's...

  17. 5 CFR 1651.16 - Missing and unknown beneficiaries.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Missing and unknown beneficiaries. 1651... § 1651.16 Missing and unknown beneficiaries. (a) Locate and identify beneficiaries. (1) The TSP record... one or more beneficiaries (and not all) appear to be missing, payment of part of the participant's...

  18. 5 CFR 1651.16 - Missing and unknown beneficiaries.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Missing and unknown beneficiaries. 1651... § 1651.16 Missing and unknown beneficiaries. (a) Locate and identify beneficiaries. (1) The TSP record... one or more beneficiaries (and not all) appear to be missing, payment of part of the participant's...

  19. 5 CFR 1651.16 - Missing and unknown beneficiaries.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Missing and unknown beneficiaries. 1651... § 1651.16 Missing and unknown beneficiaries. (a) Locate and identify beneficiaries. (1) The TSP record... one or more beneficiaries (and not all) appear to be missing, payment of part of the participant's...

  20. Known knowns, known unknowns and unknown unknowns in prokaryotic transposition.

    PubMed

    Siguier, Patricia; Gourbeyre, Edith; Chandler, Michael

    2017-08-01

    Although the phenomenon of transposition has been known for over 60 years, its overarching importance in modifying and streamlining genomes took some time to recognize. In spite of a robust understanding of transposition of some TE, there remain a number of important TE groups with potential high genome impact and unknown transposition mechanisms and yet others, only recently identified by bioinformatics, yet to be formally confirmed as mobile. Here, we point to some areas of limited understanding concerning well established important TE groups with DDE Tpases, to address central gaps in our knowledge of characterised Tn with other types of Tpases and finally, to highlight new potentially mobile DNA species. It is not exhaustive. Examples have been chosen to provide encouragement in the continued exploration of the considerable prokaryotic mobilome especially in light of the current threat to public health posed by the spread of multiple Ab R . Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Passive acoustic monitoring using a towed hydrophone array results in identification of a previously unknown beaked whale habitat.

    PubMed

    Yack, Tina M; Barlow, Jay; Calambokidis, John; Southall, Brandon; Coates, Shannon

    2013-09-01

    Beaked whales are diverse and species rich taxa. They spend the vast majority of their time submerged, regularly diving to depths of hundreds to thousands of meters, typically occur in small groups, and behave inconspicuously at the surface. These factors make them extremely difficult to detect using standard visual survey methods. However, recent advancements in acoustic detection capabilities have made passive acoustic monitoring (PAM) a viable alternative. Beaked whales can be discriminated from other odontocetes by the unique characteristics of their echolocation clicks. In 2009 and 2010, PAM methods using towed hydrophone arrays were tested. These methods proved highly effective for real-time detection of beaked whales in the Southern California Bight (SCB) and were subsequently implemented in 2011 to successfully detect and track beaked whales during the ongoing Southern California Behavioral Response Study. The three year field effort has resulted in (1) the successful classification and tracking of Cuvier's (Ziphius cavirostris), Baird's (Berardius bairdii), and unidentified Mesoplodon beaked whale species and (2) the identification of areas of previously unknown beaked whale habitat use. Identification of habitat use areas will contribute to a better understanding of the complex relationship between beaked whale distribution, occurrence, and preferred habitat characteristics on a relatively small spatial scale. These findings will also provide information that can be used to promote more effective management and conservation of beaked whales in the SCB, a heavily used Naval operation and training region.

  2. MoCha: Molecular Characterization of Unknown Pathways.

    PubMed

    Lobo, Daniel; Hammelman, Jennifer; Levin, Michael

    2016-04-01

    Automated methods for the reverse-engineering of complex regulatory networks are paving the way for the inference of mechanistic comprehensive models directly from experimental data. These novel methods can infer not only the relations and parameters of the known molecules defined in their input datasets, but also unknown components and pathways identified as necessary by the automated algorithms. Identifying the molecular nature of these unknown components is a crucial step for making testable predictions and experimentally validating the models, yet no specific and efficient tools exist to aid in this process. To this end, we present here MoCha (Molecular Characterization), a tool optimized for the search of unknown proteins and their pathways from a given set of known interacting proteins. MoCha uses the comprehensive dataset of protein-protein interactions provided by the STRING database, which currently includes more than a billion interactions from over 2,000 organisms. MoCha is highly optimized, performing typical searches within seconds. We demonstrate the use of MoCha with the characterization of unknown components from reverse-engineered models from the literature. MoCha is useful for working on network models by hand or as a downstream step of a model inference engine workflow and represents a valuable and efficient tool for the characterization of unknown pathways using known data from thousands of organisms. MoCha and its source code are freely available online under the GPLv3 license.

  3. Lod score curves for phase-unknown matings.

    PubMed

    Hulbert-Shearon, T; Boehnke, M; Lange, K

    1996-01-01

    For a phase-unknown nuclear family, we show that the likelihood and lod score are unimodal, and we describe conditions under which the maximum occurs at recombination fraction theta = 0, theta = 1/2, and 0 < theta < 1/2. These simply stated necessary and sufficient conditions seem to have escaped the notice of previous statistical geneticists.

  4. Characterization of unknown brominated disinfection byproducts during chlorination using ultrahigh resolution mass spectrometry.

    PubMed

    Zhang, Haifeng; Zhang, Yahe; Shi, Quan; Zheng, Hongdie; Yang, Min

    2014-03-18

    Brominated disinfection byproducts (Br-DBPs), formed from the reaction of disinfectant(s) with natural organic matter in the presence of bromide in raw water, are generally more cytotoxic and genotoxic than their chlorinated analogues. To date, only a few Br-DBPs in drinking water have been identified, while a significant portion of Br-DBPs in drinking water is still unknown. In this study, negative ion electrospray ionization ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) was used to characterize unknown Br-DBPs in artificial drinking water. In total, 441 formulas for one-bromine-containing products and 37 formulas for two-bromine-containing products, most of which had not been previously reported, were detected in the chlorinated sample. Most Br-DBPs have corresponding chlorine-containing analogues with identical CHO composition. In addition, on-resonance collision-induced dissociation (CID) of single ultrahigh resolved bromine containing mass peaks was performed in the ICR cell to isolate single bromine-containing components in a very complex natural organic matter spectrum and provide structure information. Relatively abundant neutral loss of CO2 was observed in MS-MS spectra, indicating that the unknown Br-DBPs are rich in carboxyl groups. The results demonstrate that the ESI FT-ICR MS method could provide valuable molecular composition and structure information on unknown Br-DBPs.

  5. Navigation through unknown and dynamic open spaces using topological notions

    NASA Astrophysics Data System (ADS)

    Miguel-Tomé, Sergio

    2018-04-01

    Until now, most algorithms used for navigation have had the purpose of directing system towards one point in space. However, humans communicate tasks by specifying spatial relations among elements or places. In addition, the environments in which humans develop their activities are extremely dynamic. The only option that allows for successful navigation in dynamic and unknown environments is making real-time decisions. Therefore, robots capable of collaborating closely with human beings must be able to make decisions based on the local information registered by the sensors and interpret and express spatial relations. Furthermore, when one person is asked to perform a task in an environment, this task is communicated given a category of goals so the person does not need to be supervised. Thus, two problems appear when one wants to create multifunctional robots: how to navigate in dynamic and unknown environments using spatial relations and how to accomplish this without supervision. In this article, a new architecture to address the two cited problems is presented, called the topological qualitative navigation architecture. In previous works, a qualitative heuristic called the heuristic of topological qualitative semantics (HTQS) has been developed to establish and identify spatial relations. However, that heuristic only allows for establishing one spatial relation with a specific object. In contrast, navigation requires a temporal sequence of goals with different objects. The new architecture attains continuous generation of goals and resolves them using HTQS. Thus, the new architecture achieves autonomous navigation in dynamic or unknown open environments.

  6. Assessment of source-specific health effects associated with an unknown number of major sources of multiple air pollutants: a unified Bayesian approach.

    PubMed

    Park, Eun Sug; Hopke, Philip K; Oh, Man-Suk; Symanski, Elaine; Han, Daikwon; Spiegelman, Clifford H

    2014-07-01

    There has been increasing interest in assessing health effects associated with multiple air pollutants emitted by specific sources. A major difficulty with achieving this goal is that the pollution source profiles are unknown and source-specific exposures cannot be measured directly; rather, they need to be estimated by decomposing ambient measurements of multiple air pollutants. This estimation process, called multivariate receptor modeling, is challenging because of the unknown number of sources and unknown identifiability conditions (model uncertainty). The uncertainty in source-specific exposures (source contributions) as well as uncertainty in the number of major pollution sources and identifiability conditions have been largely ignored in previous studies. A multipollutant approach that can deal with model uncertainty in multivariate receptor models while simultaneously accounting for parameter uncertainty in estimated source-specific exposures in assessment of source-specific health effects is presented in this paper. The methods are applied to daily ambient air measurements of the chemical composition of fine particulate matter ([Formula: see text]), weather data, and counts of cardiovascular deaths from 1995 to 1997 for Phoenix, AZ, USA. Our approach for evaluating source-specific health effects yields not only estimates of source contributions along with their uncertainties and associated health effects estimates but also estimates of model uncertainty (posterior model probabilities) that have been ignored in previous studies. The results from our methods agreed in general with those from the previously conducted workshop/studies on the source apportionment of PM health effects in terms of number of major contributing sources, estimated source profiles, and contributions. However, some of the adverse source-specific health effects identified in the previous studies were not statistically significant in our analysis, which probably resulted because we

  7. The microbiology "unknown" misadventure.

    PubMed

    Boyer, B; DeBenedictis, K J; Master, R; Jones, R S

    1998-06-01

    A 19-year-old nursing student was hospitalized after several days of nausea, vomiting, diarrhea, and fevers. Salmonella paratyphi A was isolated from multiple blood cultures. Because this is an unlikely isolate in the United States, an investigation ensued. Two and a half weeks earlier, the student had been working on a microbiology laboratory exercise "unknown." Both the "unknown" organism and the patient's blood culture isolates were identified as S. paratyphi A, with the same biochemical reactions and antimicrobial susceptibility results. The patient's condition improved with antibiotic therapy, and she was discharged after 9 days in the hospital. Conclusions related to our investigation are as follows: (1) relatively virulent organisms were unnecessary to fulfill the laboratory objectives, (2) pipetting by mouth must never be allowed, (3) proper labeling of specimens is imperative, (4) instructors should have knowledge of laboratory safety regulations, and (5) it is the obligation of laboratory directors and administrators to provide a safe academic environment.

  8. 16. Photocopy of photograph (Photographer unknown, Date unknown) SUPPOSED OLDEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. Photocopy of photograph (Photographer unknown, Date unknown) SUPPOSED OLDEST VIEW OF MAIN AND EAST ELEVATIONS - Caleb Pusey House, 15 Race Street (Landingford Plantation), Upland, Delaware County, PA

  9. Chronic kidney disease of unknown etiology in Sri Lanka.

    PubMed

    Rajapakse, Senaka; Shivanthan, Mitrakrishnan Chrishan; Selvarajah, Mathu

    2016-07-01

    In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1-22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization.

  10. 7. Photocopy of painting (Source unknown, Date unknown) EXTERIOR SOUTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Photocopy of painting (Source unknown, Date unknown) EXTERIOR SOUTH FRONT VIEW OF MISSION AND CONVENTO AFTER 1913 - Mission San Francisco Solano de Sonoma, First & Spain Streets, Sonoma, Sonoma County, CA

  11. 6. Photocopy of photograph Photographer unknown, date unknown DETAIL OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photocopy of photograph Photographer unknown, date unknown DETAIL OF BOTTOM OF DRUM, SHOWING DECORATIVE MOLDING OF DRUM AND ARCHES: NOTE EFFECT OF BOX BEAMS CREATED BY MOLDING - University of Kentucky, Carnegie Library, Lexington, Fayette County, KY

  12. The Epipolythiodiketopiperazine Gene Cluster in Claviceps purpurea: Dysfunctional Cytochrome P450 Enzyme Prevents Formation of the Previously Unknown Clapurines.

    PubMed

    Dopstadt, Julian; Neubauer, Lisa; Tudzynski, Paul; Humpf, Hans-Ulrich

    2016-01-01

    Claviceps purpurea is an important food contaminant and well known for the production of the toxic ergot alkaloids. Apart from that, little is known about its secondary metabolism and not all toxic substances going along with the food contamination with Claviceps are known yet. We explored the metabolite profile of a gene cluster in C. purpurea with a high homology to gene clusters, which are responsible for the formation of epipolythiodiketopiperazine (ETP) toxins in other fungi. By overexpressing the transcription factor, we were able to activate the cluster in the standard C. purpurea strain 20.1. Although all necessary genes for the formation of the characteristic disulfide bridge were expressed in the overexpression mutants, the fungus did not produce any ETPs. Isolation of pathway intermediates showed that the common biosynthetic pathway stops after the first steps. Our results demonstrate that hydroxylation of the diketopiperazine backbone is the critical step during the ETP biosynthesis. Due to a dysfunctional enzyme, the fungus is not able to produce toxic ETPs. Instead, the pathway end-products are new unusual metabolites with a unique nitrogen-sulfur bond. By heterologous expression of the Leptosphaeria maculans cytochrome P450 encoding gene sirC, we were able to identify the end-products of the ETP cluster in C. purpurea. The thioclapurines are so far unknown ETPs, which might contribute to the toxicity of other C. purpurea strains with a potentially intact ETP cluster.

  13. The Epipolythiodiketopiperazine Gene Cluster in Claviceps purpurea: Dysfunctional Cytochrome P450 Enzyme Prevents Formation of the Previously Unknown Clapurines

    PubMed Central

    Tudzynski, Paul; Humpf, Hans-Ulrich

    2016-01-01

    Claviceps purpurea is an important food contaminant and well known for the production of the toxic ergot alkaloids. Apart from that, little is known about its secondary metabolism and not all toxic substances going along with the food contamination with Claviceps are known yet. We explored the metabolite profile of a gene cluster in C. purpurea with a high homology to gene clusters, which are responsible for the formation of epipolythiodiketopiperazine (ETP) toxins in other fungi. By overexpressing the transcription factor, we were able to activate the cluster in the standard C. purpurea strain 20.1. Although all necessary genes for the formation of the characteristic disulfide bridge were expressed in the overexpression mutants, the fungus did not produce any ETPs. Isolation of pathway intermediates showed that the common biosynthetic pathway stops after the first steps. Our results demonstrate that hydroxylation of the diketopiperazine backbone is the critical step during the ETP biosynthesis. Due to a dysfunctional enzyme, the fungus is not able to produce toxic ETPs. Instead, the pathway end-products are new unusual metabolites with a unique nitrogen-sulfur bond. By heterologous expression of the Leptosphaeria maculans cytochrome P450 encoding gene sirC, we were able to identify the end-products of the ETP cluster in C. purpurea. The thioclapurines are so far unknown ETPs, which might contribute to the toxicity of other C. purpurea strains with a potentially intact ETP cluster. PMID:27390873

  14. Screening for Albuminuria Identifies Individuals at Increased Renal Risk

    PubMed Central

    van der Velde, Marije; Halbesma, Nynke; de Charro, Frank T.; Bakker, Stephan J.L.; de Zeeuw, Dick; de Jong, Paul E.; Gansevoort, Ronald T.

    2009-01-01

    It is unknown whether screening for albuminuria in the general population identifies individuals at increased risk for renal replacement therapy (RRT) or accelerated loss of renal function. Here, in a general population-based cohort of 40,854 individuals aged 28 to 75 yr, we collected a first morning void for measurement of urinary albumin. In a subset of 6879 individuals, we measured 24-h urinary albumin excretion and estimated GFR at baseline and during 6 yr of follow-up. Linkage with the national RRT registry identified 45 individuals who started RRT during 9 yr of follow-up. The quantity of albuminuria was associated with increased renal risk: the higher the level of albuminuria, the higher the risk of need for renal replacement therapy and the more rapid renal function decline. A urinary albumin concentration of ≥20 mg/L identified individuals who started RRT during follow-up with 58% sensitivity and 92% specificity. Of the identified individuals, 39% were previously unknown to have impaired renal function, and 50% were not being medically treated. Restricting screening to high-risk groups (e.g., known hypertension, diabetes, cardiovascular disease [CVD], older age) reduced the sensitivity of the test only marginally but failed to identify 45% of individuals with micro- and macroalbuminuria. In conclusion, individuals with elevated levels of urinary albumin are at increased risk for RRT and accelerated loss of renal function. Screening for albuminuria identifies patients at increased risk for progressive renal disease, 40 to 50% of whom were previously undiagnosed or untreated. PMID:19211710

  15. 396. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    396. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; EAST BAY CROSSING; CANTILEVER STRUCTURE; DETAILS I; DRG. NO. 68 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  16. 393. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    393. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; EAST BAY CROSSING; PIER-E3; GENERAL DETAILS; DRG. NO. 47 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  17. 397. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    397. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; EAST BAY CROSSING; CANTILEVER STRUCTURE; DETAILS II; DRG. NO. 69 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  18. 398. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    398. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; EAST BAY CROSSING; GENERAL PLAN; TOWER E-9; DRG. NO. 59 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  19. Quantum key distribution with an unknown and untrusted source

    NASA Astrophysics Data System (ADS)

    Zhao, Yi; Qi, Bing; Lo, Hoi-Kwong

    2008-05-01

    The security of a standard bidirectional “plug-and-play” quantum key distribution (QKD) system has been an open question for a long time. This is mainly because its source is equivalently controlled by an eavesdropper, which means the source is unknown and untrusted. Qualitative discussion on this subject has been made previously. In this paper, we solve this question directly by presenting the quantitative security analysis on a general class of QKD protocols whose sources are unknown and untrusted. The securities of standard Bennett-Brassard 1984 protocol, weak+vacuum decoy state protocol, and one-decoy state protocol, with unknown and untrusted sources are rigorously proved. We derive rigorous lower bounds to the secure key generation rates of the above three protocols. Our numerical simulation results show that QKD with an untrusted source gives a key generation rate that is close to that with a trusted source.

  20. 400. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    400. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; EAST BAY CROSSING; PIER E-6 TO E-23; TYPICAL DETAILS; DRG. NO. 52 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  1. Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements

    PubMed Central

    Falaleeva, Marina; Zurek, Oliwia W.; Watkins, Robert L.; Reed, Robert W.; Ali, Hadeel; Sumby, Paul; Voyich, Jovanka M.

    2014-01-01

    The important human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that the hasABC operon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription of hasABC, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion of hasS or of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through, hasA transcription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence. PMID:25287924

  2. Chronic kidney disease of unknown etiology in Sri Lanka

    PubMed Central

    2016-01-01

    Introduction In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1–22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. Methods A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. Results Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. Discussion Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization. PMID:27399161

  3. Females use self-referent cues to avoid mating with previous mates.

    PubMed

    Ivy, Tracie M; Weddle, Carie B; Sakaluk, Scott K

    2005-12-07

    Females of many species mate repeatedly throughout their lives, often with many different males (polyandry). Females can secure genetic benefits by maximizing their diversity of mating partners, and might be expected, therefore, to forego matings with previous partners in favour of novel males. Indeed, a female preference for novel mating partners has been shown in several taxa, but the mechanism by which females distinguish between novel males and previous mates remains unknown. We show that female crickets (Gryllodes sigillatus) mark males with their own unique chemical signatures during mating, enabling females to recognize prior mates in subsequent encounters and to avoid remating with them. Because self-referent chemosensory cues provide females with a simple, but reliable mechanism of identifying individuals with whom they have mated without requiring any special cognitive ability, they may be a widespread means by which females across a broad range of animal mating systems maximize the genetic benefits of polyandry.

  4. Females use self-referent cues to avoid mating with previous mates

    PubMed Central

    Ivy, Tracie M; Weddle, Carie B; Sakaluk, Scott K

    2005-01-01

    Females of many species mate repeatedly throughout their lives, often with many different males (polyandry). Females can secure genetic benefits by maximizing their diversity of mating partners, and might be expected, therefore, to forego matings with previous partners in favour of novel males. Indeed, a female preference for novel mating partners has been shown in several taxa, but the mechanism by which females distinguish between novel males and previous mates remains unknown. We show that female crickets (Gryllodes sigillatus) mark males with their own unique chemical signatures during mating, enabling females to recognize prior mates in subsequent encounters and to avoid remating with them. Because self-referent chemosensory cues provide females with a simple, but reliable mechanism of identifying individuals with whom they have mated without requiring any special cognitive ability, they may be a widespread means by which females across a broad range of animal mating systems maximize the genetic benefits of polyandry. PMID:16271971

  5. Quantum key distribution with an unknown and untrusted source

    NASA Astrophysics Data System (ADS)

    Zhao, Yi; Qi, Bing; Lo, Hoi-Kwong

    2009-03-01

    The security of a standard bi-directional ``plug & play'' quantum key distribution (QKD) system has been an open question for a long time. This is mainly because its source is equivalently controlled by an eavesdropper, which means the source is unknown and untrusted. Qualitative discussion on this subject has been made previously. In this paper, we present the first quantitative security analysis on a general class of QKD protocols whose sources are unknown and untrusted. The securities of standard BB84 protocol, weak+vacuum decoy state protocol, and one-decoy decoy state protocol, with unknown and untrusted sources are rigorously proved. We derive rigorous lower bounds to the secure key generation rates of the above three protocols. Our numerical simulation results show that QKD with an untrusted source gives a key generation rate that is close to that with a trusted source. Our work is published in [1]. [4pt] [1] Y. Zhao, B. Qi, and H.-K. Lo, Phys. Rev. A, 77:052327 (2008).

  6. Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

    PubMed Central

    Zubair, Niha; Luis Ambite, Jose; Bush, William S.; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne H-H.; Absher, Devin; Assimes, Themistocles L.; Bielinski, Suzette J.; Bottinger, Erwin P.; Buzkova, Petra; Chuang, Lee-Ming; Chung, Ren-Hua; Cochran, Barbara; Dumitrescu, Logan; Gottesman, Omri; Haessler, Jeffrey W.; Haiman, Christopher; Heiss, Gerardo; Hsiung, Chao A.; Hung, Yi-Jen; Hwu, Chii-Min; Juang, Jyh-Ming J.; Le Marchand, Loic; Lee, I-Te; Lee, Wen-Jane; Lin, Li-An; Lin, Danyu; Lin, Shih-Yi; Mackey, Rachel H.; Martin, Lisa W.; Pasaniuc, Bogdan; Peters, Ulrike; Predazzi, Irene; Quertermous, Thomas; Reiner, Alex P.; Robinson, Jennifer; Rotter, Jerome I.; Ryckman, Kelli K.; Schreiner, Pamela J.; Stahl, Eli; Tao, Ran; Tsai, Michael Y.; Waite, Lindsay L.; Wang, Tzung-Dau; Buyske, Steven; Ida Chen, Yii-Der; Cheng, Iona; Crawford, Dana C.; Loos, Ruth J.F.; Rich, Stephen S.; Fornage, Myriam; North, Kari E.; Kooperberg, Charles; Carty, Cara L.

    2016-01-01

    Abstract Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies. PMID:28426890

  7. Influence of multiple categories on the prediction of unknown properties

    PubMed Central

    Verde, Michael F.; Murphy, Gregory L.; Ross, Brian H.

    2006-01-01

    Knowing an item's category helps us predict its unknown properties. Previous studies suggest that when asked to evaluate the probability of an unknown property, people tend to consider only an item's most likely category, ignoring alternative categories. In the present study, property prediction took the form of either a probability rating or a speeded, binary-choice judgment. Consistent with past findings, subjects ignored alternative categories in their probability ratings. However, their binary-choice judgments were influenced by alternative categories. This novel finding suggests that the way category knowledge is used in prediction depends critically on the form of the prediction. PMID:16156183

  8. 414. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    414. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; DIVISION OF SAN FRANCISCO BAY TOLL CROSSINGS; SAN FRANCISCO OAKLAND BAY BRIDGE RECONSTRUCTION; STEEL WORK - WEST BAY; TYPICAL SECTIONS; SHEET NO. 5; DRAWING NO. C-4028-5R - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  9. Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance.

    PubMed

    Li, Bian; Mendenhall, Jeffrey L; Kroncke, Brett M; Taylor, Keenan C; Huang, Hui; Smith, Derek K; Vanoye, Carlos G; Blume, Jeffrey D; George, Alfred L; Sanders, Charles R; Meiler, Jens

    2017-10-01

    An emerging standard-of-care for long-QT syndrome uses clinical genetic testing to identify genetic variants of the KCNQ1 potassium channel. However, interpreting results from genetic testing is confounded by the presence of variants of unknown significance for which there is inadequate evidence of pathogenicity. In this study, we curated from the literature a high-quality set of 107 functionally characterized KCNQ1 variants. Based on this data set, we completed a detailed quantitative analysis on the sequence conservation patterns of subdomains of KCNQ1 and the distribution of pathogenic variants therein. We found that conserved subdomains generally are critical for channel function and are enriched with dysfunctional variants. Using this experimentally validated data set, we trained a neural network, designated Q1VarPred, specifically for predicting the functional impact of KCNQ1 variants of unknown significance. The estimated predictive performance of Q1VarPred in terms of Matthew's correlation coefficient and area under the receiver operating characteristic curve were 0.581 and 0.884, respectively, superior to the performance of 8 previous methods tested in parallel. Q1VarPred is publicly available as a web server at http://meilerlab.org/q1varpred. Although a plethora of tools are available for making pathogenicity predictions over a genome-wide scale, previous tools fail to perform in a robust manner when applied to KCNQ1. The contrasting and favorable results for Q1VarPred suggest a promising approach, where a machine-learning algorithm is tailored to a specific protein target and trained with a functionally validated data set to calibrate informatics tools. © 2017 American Heart Association, Inc.

  10. 413. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    413. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; DIVISION OF SAN FRANCISCO BAY TOLL CROSSINGS; SAN FRANCISCO OAKLAND BAY BRIDGE RECONSTRUCTION; STEEL WORK - WEST BAY; CONTINUOUS SPANS - LONGITUDINAL GIRDERS; SHEET NO. 18; DRAWING NO. C-4028-18R - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  11. 14. Photocopy of photograph (source unknown) photographer unknown pre1885 NORTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Photocopy of photograph (source unknown) photographer unknown pre-1885 NORTH SIDE AND WEST FRONT (NOTE ABSENCE OF DORMER ON GAMBREL ROOF OF ELL) (Illustration #6 of Data Report included in Field Records) - Narbonne House, 71 Essex Street, Salem, Essex County, MA

  12. 415. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    415. Delineator Unknown Date Unknown STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; DIVISION OF SAN FRANCISCO BAY TOLL CROSSINGS; SAN FRANCISCO OAKLAND BAY BRIDGE RECONSTRUCTION; STEEL WORK - WEST BAY; Y.B. ANCHORAGE - FLOOR BEAMS YA-5 AND BENT 3; SHEET NO. 22; DRAWING NO. C-4028-22R - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  13. Exploring the Unknown

    ERIC Educational Resources Information Center

    Pallant, Amy; Pryputniewicz, Sarah; Lee, Hee-Sun

    2012-01-01

    Scientists, and science in general, move from the unknown to increasing levels of certainty. Teaching students about science means encouraging them to embrace and investigate the unknown, make reliable scientific claims, justify those claims with evidence, and evaluate the quality of the evidence. In all areas of science--and especially in…

  14. MUSIC-type imaging of small perfectly conducting cracks with an unknown frequency

    NASA Astrophysics Data System (ADS)

    Park, Won-Kwang

    2015-09-01

    MUltiple SIgnal Classification (MUSIC) is a famous non-iterative detection algorithm in inverse scattering problems. However, when the applied frequency is unknown, inaccurate locations are identified via MUSIC. This fact has been confirmed through numerical simulations. However, the reason behind this phenomenon has not been investigated theoretically. Motivated by this fact, we identify the structure of MUSIC-type imaging functionals with unknown frequency, by establishing a relationship with Bessel functions of order zero of the first kind. Through this, we can explain why inaccurate results appear.

  15. A Previously Unknown Path to Corpuscularism in the Seventeenth Century: Santorio’s Marginalia to the Commentaria in Primam Fen Primi Libri Canonis Avicennae (1625)

    PubMed Central

    Bigotti, Fabrizio

    2017-01-01

    This paper presents some of Santorio's marginalia to his Commentaria in primam fen primi libri Canonis Avicennae (Venice, 1625), which I identified in the Sloane Collection of the British Library in 2016, as well as the evidence for their authorship. The name of the Venetian physician Santorio Santori (1561–1636) is linked with the introduction of quantification in medicine and with the invention of precision instruments that, displayed for the first time in this work, laid down the foundations for what we today understand as evidence-based medicine. But Santorio's monumentale opus also contains evidence of many quantified experiments and displays his ideas on mixtures, structure of matter and corpuscles, which are in many cases clarified and completed by the new marginalia. These ideas testify to an early interest in chemistry within the Medical School of Padua which predates both Galileo and Sennert and which has hitherto been unknown. PMID:28350287

  16. FDG PET detection of unknown primary tumors.

    PubMed

    Bohuslavizki, K H; Klutmann, S; Kröger, S; Sonnemann, U; Buchert, R; Werner, J A; Mester, J; Clausen, M

    2000-05-01

    The management of patients presenting with metastases of unknown primary origin remains a clinical challenge despite a large variety of imaging modalities. The aim of this study was to evaluate FDG PET in detecting the sites of primary cancer in these patients. Fifty-three patients with metastatic cervical adenopathy (n = 44) or extracervical metastases (n = 9) of unknown primary origin were included after extensive but inconclusive conventional diagnostic work-up. Patients received 370 MBq FDG (10 mCi) intravenously, and whole-body images were acquired at 60 min after injection. Clinical, surgical, and histopathologic findings and complete correlative imaging were used to assess the results. In 27 of 53 patients FDG PET showed focal tracer accumulations corresponding to potential primary tumor sites located in the lungs (n = 12), the palatine tonsil (n = 5), the salivary glands (n = 2), the nasopharynx (n = 1), the oropharynx (n = 3), the maxillary sinus (n = 1), and the larynx (n = 1). Moreover, in 2 patients FDG PET revealed lesions suspected to be tumors in the breast and the ileocolonic area. In 20 (37.8%) of these 53 patients FDG PET was true-positive, identifying the primary tumor in the lungs (n = 10), the head and neck region (n = 8), the breast (n = 1), and the ileocolonic area (n = 1). In 6 of 27 patients FDG PET was false-positive, predominantly identifying suspicious areas in the palatine tonsil (n = 3). One patient denied further diagnostic work-up after PET; thus, positive PET could not be evaluated. In 26 of 53 patients PET did not reveal lesions suspected to be the primary. However, primary tumors were not found in these patients at clinical follow-up. FDG PET is a valuable diagnostic tool in patients with cancer of unknown primary because it imaged unknown primary tumors in about one third of all patients investigated. In addition, FDG PET assists in both guiding biopsies for histologic evaluation and selecting the appropriate treatment protocols

  17. Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci.

    PubMed

    Zubair, Niha; Graff, Mariaelisa; Luis Ambite, Jose; Bush, William S; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne H-H; Absher, Devin; Assimes, Themistocles L; Bielinski, Suzette J; Bottinger, Erwin P; Buzkova, Petra; Chuang, Lee-Ming; Chung, Ren-Hua; Cochran, Barbara; Dumitrescu, Logan; Gottesman, Omri; Haessler, Jeffrey W; Haiman, Christopher; Heiss, Gerardo; Hsiung, Chao A; Hung, Yi-Jen; Hwu, Chii-Min; Juang, Jyh-Ming J; Le Marchand, Loic; Lee, I-Te; Lee, Wen-Jane; Lin, Li-An; Lin, Danyu; Lin, Shih-Yi; Mackey, Rachel H; Martin, Lisa W; Pasaniuc, Bogdan; Peters, Ulrike; Predazzi, Irene; Quertermous, Thomas; Reiner, Alex P; Robinson, Jennifer; Rotter, Jerome I; Ryckman, Kelli K; Schreiner, Pamela J; Stahl, Eli; Tao, Ran; Tsai, Michael Y; Waite, Lindsay L; Wang, Tzung-Dau; Buyske, Steven; Ida Chen, Yii-Der; Cheng, Iona; Crawford, Dana C; Loos, Ruth J F; Rich, Stephen S; Fornage, Myriam; North, Kari E; Kooperberg, Charles; Carty, Cara L

    2016-12-15

    Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Sequencing the Unknown

    NASA Image and Video Library

    2017-12-19

    Being able to identify microbes in real time aboard the International Space Station, without having to send them back to Earth for identification first, would be revolutionary for the world of microbiology and space exploration, and the Genes in Space-3 team turned that possibility into a reality this year when it completed the first-ever sample-to-sequence process entirely aboard the space station. This advance could aid in the ability to diagnose and treat astronaut ailments in real time, as well as assisting in the identification of DNA-based life on other planets. It could also benefit other experiments aboard the orbiting laboratory. HD Download: https://archive.org/details/jsc2017m001160_Sequencing_the_Unknown _______________________________________ FOLLOW THE SPACE STATION! Twitter: https://twitter.com/Space_Station Facebook: https://www.facebook.com/ISS Instagram: https://instagram.com/iss/

  19. Pattern Recognition Algorithm for High-Sensitivity Odorant Detection in Unknown Environments

    NASA Technical Reports Server (NTRS)

    Duong, Tuan A.

    2012-01-01

    In a realistic odorant detection application environment, the collected sensory data is a mix of unknown chemicals with unknown concentrations and noise. The identification of the odorants among these mixtures is a challenge in data recognition. In addition, deriving their individual concentrations in the mix is also a challenge. A deterministic analytical model was developed to accurately identify odorants and calculate their concentrations in a mixture with noisy data.

  20. Knowns and unknowns in metabolomics identified by multidimensional NMR and hybrid MS/NMR methods

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

    Bingol, Kerem; Brüschweiler, Rafael

    Metabolomics continues to make rapid progress through the development of new and better methods and their applications to gain insight into the metabolism of a wide range of different biological systems from a systems biology perspective. Customization of NMR databases and search tools allows the faster and more accurate identification of known metabolites, whereas the identification of unknowns, without a need for extensive purification, requires new strategies to integrate NMR with mass spectrometry, cheminformatics, and computational methods. For some applications, the use of covalent and non-covalent attachments in the form of labeled tags or nanoparticles can significantly reduce the complexitymore » of these tasks.« less

  1. Parameter identifiability of linear dynamical systems

    NASA Technical Reports Server (NTRS)

    Glover, K.; Willems, J. C.

    1974-01-01

    It is assumed that the system matrices of a stationary linear dynamical system were parametrized by a set of unknown parameters. The question considered here is, when can such a set of unknown parameters be identified from the observed data? Conditions for the local identifiability of a parametrization are derived in three situations: (1) when input/output observations are made, (2) when there exists an unknown feedback matrix in the system and (3) when the system is assumed to be driven by white noise and only output observations are made. Also a sufficient condition for global identifiability is derived.

  2. Identification of Unknown Contaminants in Water Samples from ISS Employing Liquid Chromatography/Mass Spectrometry/Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Rutz, Jeffrey A.; Schultz, John R.

    2008-01-01

    Mass Spectrometry/Mass Spectrometry (MS/MS) is a powerful technique for identifying unknown organic compounds. For non-volatile or thermally unstable unknowns dissolved in liquids, liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) is often the variety of MS/MS used for the identification. One type of LC/MS/MS that is rapidly becoming popular is time-of-flight (TOF) mass spectrometry. This technique is now in use at the Johnson Space Center for identification of unknown nonvolatile organics in water samples from the space program. An example of the successful identification of one unknown is reviewed in detail in this paper. The advantages of time-of-flight instrumentation are demonstrated through this example as well as the strategy employed in using time-of-flight data to identify unknowns.

  3. Component spectra extraction from terahertz measurements of unknown mixtures.

    PubMed

    Li, Xian; Hou, D B; Huang, P J; Cai, J H; Zhang, G X

    2015-10-20

    The aim of this work is to extract component spectra from unknown mixtures in the terahertz region. To that end, a method, hard modeling factor analysis (HMFA), was applied to resolve terahertz spectral matrices collected from the unknown mixtures. This method does not require any expertise of the user and allows the consideration of nonlinear effects such as peak variations or peak shifts. It describes the spectra using a peak-based nonlinear mathematic model and builds the component spectra automatically by recombination of the resolved peaks through correlation analysis. Meanwhile, modifications on the method were made to take the features of terahertz spectra into account and to deal with the artificial baseline problem that troubles the extraction process of some terahertz spectra. In order to validate the proposed method, simulated wideband terahertz spectra of binary and ternary systems and experimental terahertz absorption spectra of amino acids mixtures were tested. In each test, not only the number of pure components could be correctly predicted but also the identified pure spectra had a good similarity with the true spectra. Moreover, the proposed method associated the molecular motions with the component extraction, making the identification process more physically meaningful and interpretable compared to other methods. The results indicate that the HMFA method with the modifications can be a practical tool for identifying component terahertz spectra in completely unknown mixtures. This work reports the solution to this kind of problem in the terahertz region for the first time, to the best of the authors' knowledge, and represents a significant advance toward exploring physical or chemical mechanisms of unknown complex systems by terahertz spectroscopy.

  4. Using fragmentation trees and mass spectral trees for identifying unknown compounds in metabolomics.

    PubMed

    Vaniya, Arpana; Fiehn, Oliver

    2015-06-01

    Identification of unknown metabolites is the bottleneck in advancing metabolomics, leaving interpretation of metabolomics results ambiguous. The chemical diversity of metabolism is vast, making structure identification arduous and time consuming. Currently, comprehensive analysis of mass spectra in metabolomics is limited to library matching, but tandem mass spectral libraries are small compared to the large number of compounds found in the biosphere, including xenobiotics. Resolving this bottleneck requires richer data acquisition and better computational tools. Multi-stage mass spectrometry (MSn) trees show promise to aid in this regard. Fragmentation trees explore the fragmentation process, generate fragmentation rules and aid in sub-structure identification, while mass spectral trees delineate the dependencies in multi-stage MS of collision-induced dissociations. This review covers advancements over the past 10 years as a tool for metabolite identification, including algorithms, software and databases used to build and to implement fragmentation trees and mass spectral annotations.

  5. A population genomic scan in Chorthippus grasshoppers unveils previously unknown phenotypic divergence.

    PubMed

    Berdan, Emma L; Mazzoni, Camila J; Waurick, Isabelle; Roehr, Johannes T; Mayer, Frieder

    2015-08-01

    Understanding the genetics of speciation and the processes that drive it is a central goal of evolutionary biology. Grasshoppers of the Chorthippus species group differ strongly in calling song (and corresponding female preferences) but are exceedingly similar in other characteristics such as morphology. Here, we performed a population genomic scan on three Chorthippus species (Chorthippus biguttulus, C. mollis and C. brunneus) to gain insight into the genes and processes involved in divergence and speciation in this group. Using an RNA-seq approach, we examined functional variation between the species by calling SNPs for each of the three species pairs and using FST -based approaches to identify outliers. We found approximately 1% of SNPs in each comparison to be outliers. Between 37% and 40% of these outliers were nonsynonymous SNPs (as opposed to a global level of 17%) indicating that we recovered loci under selection. Among the outliers were several genes that may be involved in song production and hearing as well as genes involved in other traits such as food preferences and metabolism. Differences in food preferences between species were confirmed with a behavioural experiment. This indicates that multiple phenotypic differences implicating multiple evolutionary processes (sexual selection and natural selection) are present between the species. © 2015 John Wiley & Sons Ltd.

  6. ENU Mutagenesis in Mice Identifies Candidate Genes For Hypogonadism

    PubMed Central

    Weiss, Jeffrey; Hurley, Lisa A.; Harris, Rebecca M.; Finlayson, Courtney; Tong, Minghan; Fisher, Lisa A.; Moran, Jennifer L.; Beier, David R.; Mason, Christopher; Jameson, J. Larry

    2012-01-01

    Genome-wide mutagenesis was performed in mice to identify candidate genes for male infertility, for which the predominant causes remain idiopathic. Mice were mutagenized using N-ethyl-N-nitrosourea (ENU), bred, and screened for phenotypes associated with the male urogenital system. Fifteen heritable lines were isolated and chromosomal loci were assigned using low density genome-wide SNP arrays. Ten of the fifteen lines were pursued further using higher resolution SNP analysis to narrow the candidate gene regions. Exon sequencing of candidate genes identified mutations in mice with cystic kidneys (Bicc1), cryptorchidism (Rxfp2), restricted germ cell deficiency (Plk4), and severe germ cell deficiency (Prdm9). In two other lines with severe hypogonadism candidate sequencing failed to identify mutations, suggesting defects in genes with previously undocumented roles in gonadal function. These genomic intervals were sequenced in their entirety and a candidate mutation was identified in SnrpE in one of the two lines. The line harboring the SnrpE variant retains substantial spermatogenesis despite small testis size, an unusual phenotype. In addition to the reproductive defects, heritable phenotypes were observed in mice with ataxia (Myo5a), tremors (Pmp22), growth retardation (unknown gene), and hydrocephalus (unknown gene). These results demonstrate that the ENU screen is an effective tool for identifying potential causes of male infertility. PMID:22258617

  7. Fatal Metacestode Infection in Bornean Orangutan Caused by Unknown Versteria Species

    PubMed Central

    Gendron-Fitzpatrick, Annette; Deering, Kathleen M.; Wallace, Roberta S.; Clyde, Victoria L.; Lauck, Michael; Rosen, Gail E.; Bennett, Andrew J.; Greiner, Ellis C.; O’Connor, David H.

    2014-01-01

    A captive juvenile Bornean orangutan (Pongo pygmaeus) died from an unknown disseminated parasitic infection. Deep sequencing of DNA from infected tissues, followed by gene-specific PCR and sequencing, revealed a divergent species within the newly proposed genus Versteria (Cestoda: Taeniidae). Versteria may represent a previously unrecognized risk to primate health. PMID:24377497

  8. Metal alloy identifier

    DOEpatents

    Riley, William D.; Brown, Jr., Robert D.

    1987-01-01

    To identify the composition of a metal alloy, sparks generated from the alloy are optically observed and spectrographically analyzed. The spectrographic data, in the form of a full-spectrum plot of intensity versus wavelength, provide the "signature" of the metal alloy. This signature can be compared with similar plots for alloys of known composition to establish the unknown composition by a positive match with a known alloy. An alternative method is to form intensity ratios for pairs of predetermined wavelengths within the observed spectrum and to then compare the values of such ratios with similar values for known alloy compositions, thereby to positively identify the unknown alloy composition.

  9. Accurate Identification of Unknown and Known Metabolic Mixture Components by Combining 3D NMR with Fourier Transform Ion Cyclotron Resonance Tandem Mass Spectrometry.

    PubMed

    Wang, Cheng; He, Lidong; Li, Da-Wei; Bruschweiler-Li, Lei; Marshall, Alan G; Brüschweiler, Rafael

    2017-10-06

    Metabolite identification in metabolomics samples is a key step that critically impacts downstream analysis. We recently introduced the SUMMIT NMR/mass spectrometry (MS) hybrid approach for the identification of the molecular structure of unknown metabolites based on the combination of NMR, MS, and combinatorial cheminformatics. Here, we demonstrate the feasibility of the approach for an untargeted analysis of both a model mixture and E. coli cell lysate based on 2D/3D NMR experiments in combination with Fourier transform ion cyclotron resonance MS and MS/MS data. For 19 of the 25 model metabolites, SUMMIT yielded complete structures that matched those in the mixture independent of database information. Of those, seven top-ranked structures matched those in the mixture, and four of those were further validated by positive ion MS/MS. For five metabolites, not part of the 19 metabolites, correct molecular structural motifs could be identified. For E. coli, SUMMIT MS/NMR identified 20 previously known metabolites with three or more 1 H spins independent of database information. Moreover, for 15 unknown metabolites, molecular structural fragments were determined consistent with their spin systems and chemical shifts. By providing structural information for entire metabolites or molecular fragments, SUMMIT MS/NMR greatly assists the targeted or untargeted analysis of complex mixtures of unknown compounds.

  10. Uncovering the unknown: A grounded theory study exploring the impact of self-awareness on the culture of feedback in residency education.

    PubMed

    Ramani, Subha; Könings, Karen; Mann, Karen V; van der Vleuten, Cees

    2017-10-01

    Self-assessment and reflection are essential for meaningful feedback. We aimed to explore whether the well-known Johari window model of self-awareness could guide feedback conversations between faculty and residents and enhance the institutional feedback culture. We had previously explored perceptions of residents and faculty regarding sociocultural factors impacting feedback. We re-analyzed data targeting themes related to self-assessment, reflection, feedback seeking and acceptance, aiming to generate individual and institutional feedback strategies applicable to each quadrant of the window. We identified the following themes for each quadrant: (1) Behaviors known to self and others - Validating the known; (2) Behaviors unknown to self but known to others - Accepting the blind; (3) Behaviors known to self and unknown to others - Disclosure of hidden; and (4) Behaviors unknown to self and others - Uncovering the unknown. Normalizing self-disclosure of limitations, encouraging feedback seeking, training in nonjudgmental feedback and providing opportunities for longitudinal relationships could promote self-awareness, ultimately expanding the "open" quadrant of the Johari window. The Johari window, a model of self-awareness in interpersonal communications, could provide a robust framework for individuals to improve their feedback conversations and institutions to design feedback initiatives that enhance its quality and impact.

  11. LC-MS/MS screening strategy for unknown adducts to N-terminal valine in hemoglobin applied to smokers and nonsmokers.

    PubMed

    Carlsson, Henrik; von Stedingk, Hans; Nilsson, Ulrika; Törnqvist, Margareta

    2014-12-15

    Electrophilically reactive compounds have the ability to form adducts with nucleophilic sites in DNA and proteins, constituting a risk for toxic effects. Mass spectrometric detection of adducts to N-terminal valine in hemoglobin (Hb) after detachment by modified Edman degradation procedures is one approach for in vivo monitoring of exposure to electrophilic compounds/metabolites. So far, applications have been limited to one or a few selected reactive species, such as acrylamide and its metabolite glycidamide. This article presents a novel screening strategy for unknown Hb adducts to be used as a basis for an adductomic approach. The method is based on a modified Edman procedure, FIRE, specifically developed for LC-MS/MS analysis of N-terminal valine adducts in Hb detached as fluorescein thiohydantoin (FTH) derivatives. The aim is to detect and identify a priori unknown Hb adducts in human blood samples. Screening of valine adducts was performed by stepwise scanning of precursor ions in small mass increments, monitoring four fragments common for the FTH derivative of valine with different N-substitutions in the multiple-reaction mode, covering a mass range of 135 Da (m/z 503-638). Samples from six smokers and six nonsmokers were analyzed. Control experiments were performed to compare these results with known adducts and to check for artifactual formation of adducts. In all samples of smokers and nonsmokers, seven adducts were identified, of which six have previously been studied. Nineteen unknown adducts were observed, and 14 of those exhibited fragmentation patterns similar to earlier studied FTH derivatives of adducts to valine. Identification of the unknown adducts will be the focus of future work. The presented methodology is a promising screening tool using Hb adducts to indicate exposure to potentially toxic electrophilic compounds and metabolites.

  12. Development of a Simple Tool for Identifying Alcohol Use Disorder in Female Korean Drinkers from Previous Questionnaires.

    PubMed

    Seo, Yu Ri; Kim, Jong Sung; Kim, Sung Soo; Yoon, Seok Joon; Suh, Won Yoon; Youn, Kwangmi

    2016-01-01

    This study aimed to develop a simple tool for identifying alcohol use disorders in female Korean drinkers from previous questionnaires. This research was conducted on 400 women who consumed at least one alcoholic drink during the past month and visited the health promotion center at Chungnam National University Hospital between June 2013 to May 2014. Drinking habits and alcohol use disorders were assessed by structured interviews using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnostic criteria. The subjects were also asked to answer the Alcohol Use Disorders Identification Test (AUDIT), AUDIT-Consumption, CAGE (Cut down, Annoyed, Guilty, Eye-opener), TWEAK (Tolerance, Worried, Eye-opener, Amnesia, Kut down), TACE (Tolerance, Annoyed, Cut down, Eye-opener), and NET (Normal drinker, Eye-opener, Tolerance) questionnaires. The area under receiver operating characteristic (AUROC) of each question of the questionnaires on alcohol use disorders was assessed. After combining two questions with the largest AUROC, it was compared to other previous questionnaires. Among the 400 subjects, 58 (14.5%) were identified as having an alcohol use disorder. Two questions with the largest AUROC were question no. 7 in AUDIT, "How often during the last year have you had a feeling of guilt or remorse after drinking?" and question no. 5 in AUDIT, "How often during the past year have you failed to do what was normally expected from you because of drinking?" with an AUROC (95% confidence interval [CI]) of 0.886 (0.850-0.915) and 0.862 (0.824-0.894), respectively. The AUROC (95% CI) of the combination of the two questions was 0.958 (0.934-0.976) with no significant difference as compared to the existing AUDIT with the largest AUROC. The above results suggest that the simple tool consisting of questions no. 5 and no. 7 in AUDIT is useful in identifying alcohol use disorders in Korean female drinkers.

  13. Discrete-time switching periodic adaptive control for time-varying parameters with unknown periodicity

    NASA Astrophysics Data System (ADS)

    Yu, Miao; Huang, Deqing; Yang, Wanqiu

    2018-06-01

    In this paper, we address the problem of unknown periodicity for a class of discrete-time nonlinear parametric systems without assuming any growth conditions on the nonlinearities. The unknown periodicity hides in the parametric uncertainties, which is difficult to estimate with existing techniques. By incorporating a logic-based switching mechanism, we identify the period and bound of unknown parameter simultaneously. Lyapunov-based analysis is given to demonstrate that a finite number of switchings can guarantee the asymptotic tracking for the nonlinear parametric systems. The simulation result also shows the efficacy of the proposed switching periodic adaptive control approach.

  14. The usage of fasting glucose and glycated hemoglobin for the identification of unknown type 2 diabetes in high risk patients with morbid obesity.

    PubMed

    Valderhaug, Tone G; Sharma, Archana; Kravdal, Gunnhild; Rønningen, Reidun; Nermoen, Ingrid

    2017-11-01

    In spite of increased vigilance of undiagnosed type 2 diabetes (DM2), the prevalence of unknown DM2 in subjects with morbid obesity is not known. To assess the prevalence of undiagnosed DM2 and compare the performance of glycated A1c (HbA1c) and fasting glucose (FG) for the diagnosis of DM2 and prediabetes (preDM) in patients with morbid obesity. We measured fasting glucose and HbA1c in 537 consecutive patients with morbid obesity without previously known DM2. A total of 49 (9%) patients with morbid obesity had unknown DM2 out of which 16 (33%) fulfilled both the criteria for HbA1c and FG. Out of 284 (53%) subjects with preDM, 133 (47%) fulfilled both the criteria for HbA1c and FG. Measurements of agreement for FG and HbA1c were moderate for DM2 (κ = 0.461, p < .001) and fair for preDM (κ = 0.317, p < .001). Areas under the curve for FG and HbA1c in predicting unknown DM2 were 0.970 (95% CI 0.942, 0.998) and 0.894 (95% CI 0.837, 0.951) respectively. The optimal thresholds to identify unknown DM2 were FG ≥6.6 mmol/L and HbA1c ≥ 6.1% (43 mmol/mol). The prevalence of DM2 remains high and both FG and HbA1c identify patients with unknown DM2. FG was slightly superior to HbA1c in predicting and separating patients with unknown DM2 from patients without DM2. We suggest that an FG ≥6.6 mmol/L or an HbA1c ≥6.1% (43 mmol/mol) may be used as primary cut points for the identification of unknown DM2 among patients with morbid obesity.

  15. Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology.

    PubMed

    Dubey, Divyanshu; Alqallaf, Abdulradha; Hays, Ryan; Freeman, Matthew; Chen, Kevin; Ding, Kan; Agostini, Mark; Vernino, Steven

    2017-04-01

    Autoimmune epilepsy is an underrecognized condition, and its true incidence is unknown. Identifying patients with an underlying autoimmune origin is critical because these patients' condition may remain refractory to conventional antiseizure medications but may respond to immunotherapy. To determine the prevalence of neurological autoantibodies (Abs) among adult patients with epilepsy of unknown etiology. Consecutive patients presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology were identified. Serum samples were tested for autoimmune encephalitis Abs as well as thyroperoxidase (TPO) and glutamic acid decarboxylase 65 (GAD65) Abs. An antibody prevalence in epilepsy (APE) score based on clinical characteristics was assigned prospectively. Data were collected from June 1, 2015, to June 1, 2016. Presence of neurological Abs. A score based on clinical characteristics was assigned to estimate the probability of seropositivity prior to antibody test results. Good seizure outcome was estimated on the basis of significant reduction of seizure frequency at the first follow-up or seizure freedom. Of the 127 patients (68 males and 59 females) enrolled in the study, 15 were subsequently excluded after identification of an alternative diagnosis. Serum Abs suggesting a potential autoimmune etiology were detected in 39 (34.8%) cases. More than 1 Ab was detected in 7 patients (6.3%): 3 (2.7%) had TPO-Ab and voltage-gated potassium channel complex (VGKCc) Ab, 2 (1.8%) had GAD65-Ab and VGKCc-Ab, 1 had TPO-Ab and GAD65-Ab, and 1 had anti-Hu Ab and GAD65-Ab. Thirty-two patients (28.6%) had a single Ab marker. Among 112 patients included in the study, 15 (13.4%) had TPO-Ab, 14 (12.5%) had GAD65-Ab, 12 (10.7%) had VGKCc (4 of whom were positive for leucine-rich glioma-inactivated protein 1 [LGI1] Ab), and 4 (3.6%) had N-methyl-D-aspartate receptor (NMDAR) Ab. Even after excluding TPO-Ab and low-titer GAD65-Ab, Abs strongly suggesting an

  16. Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

    DOE PAGES

    Boiteau, Rene M.; Hoyt, David W.; Nicora, Carrie D.; ...

    2018-01-17

    Here, we introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS 2), and NMR in a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS 2 approach is well suited for discovery ofmore » new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases.« less

  17. Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

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

    Boiteau, Rene M.; Hoyt, David W.; Nicora, Carrie D.

    Here, we introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS 2), and NMR in a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS 2 approach is well suited for discovery ofmore » new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases.« less

  18. Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

    PubMed Central

    Hoyt, David W.; Nicora, Carrie D.; Kinmonth-Schultz, Hannah A.; Ward, Joy K.

    2018-01-01

    We introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS2), and NMR into a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter out the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture, and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS2 approach is well suited to the discovery of new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases. PMID:29342073

  19. Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard

    EPA Science Inventory

    Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most li...

  20. Structural control and health monitoring of building structures with unknown ground excitations: Experimental investigation

    NASA Astrophysics Data System (ADS)

    He, Jia; Xu, You-Lin; Zhan, Sheng; Huang, Qin

    2017-03-01

    When health monitoring system and vibration control system both are required for a building structure, it will be beneficial and cost-effective to integrate these two systems together for creating a smart building structure. Recently, on the basis of extended Kalman filter (EKF), a time-domain integrated approach was proposed for the identification of structural parameters of the controlled buildings with unknown ground excitations. The identified physical parameters and structural state vectors were then utilized to determine the control force for vibration suppression. In this paper, the possibility of establishing such a smart building structure with the function of simultaneous damage detection and vibration suppression was explored experimentally. A five-story shear building structure equipped with three magneto-rheological (MR) dampers was built. Four additional columns were added to the building model, and several damage scenarios were then simulated by symmetrically cutting off these columns in certain stories. Two sets of earthquakes, i.e. Kobe earthquake and Northridge earthquake, were considered as seismic input and assumed to be unknown during the tests. The structural parameters and the unknown ground excitations were identified during the tests by using the proposed identification method with the measured control forces. Based on the identified structural parameters and system states, a switching control law was employed to adjust the current applied to the MR dampers for the purpose of vibration attenuation. The experimental results show that the presented approach is capable of satisfactorily identifying structural damages and unknown excitations on one hand and significantly mitigating the structural vibration on the other hand.

  1. The Unknown Variable: Identifying Learning Disabilities with Pupil Behavior Rating Scales.

    ERIC Educational Resources Information Center

    Winzer, Margret; Malarczyk, Barbara

    Difficulties in identifying learning disabilities (LD) are examined, and special problems presented by hearing impaired children with LD are considered. The value of rating scales as a quick instrument for obtaining, measuring, recording and communicating information is emphasized. Adaptations of the Pupil Rating Scale for hearing impaired…

  2. Infectious causes of fever of unknown origin.

    PubMed

    McGregor, Alastair C; Moore, David A

    2015-06-01

    The causes of fever of unknown origin (FUO) are changing because advances in clinical practice and diagnostics have facilitated the identification of some infections. A variety of bacterial infections can cause FUO, and these can be divided into those that are easy to identify using culture and those that require serological or molecular tests for identification. A number of viral, parasitic and fungal infections can also cause prolonged fever. This article summarises the clinical features and diagnostic strategy of these infections. © Royal College of Physicians 2015. All rights reserved.

  3. TaHsfA6f is a transcriptional activator that regulates a suite of heat stress protection genes in wheat (Triticum aestivum L.) including previously unknown Hsf targets

    PubMed Central

    Xue, Gang-Ping; Drenth, Janneke; McIntyre, C. Lynne

    2015-01-01

    Heat stress is a significant environmental factor adversely affecting crop yield. Crop adaptation to high-temperature environments requires transcriptional reprogramming of a suite of genes involved in heat stress protection. This study investigated the role of TaHsfA6f, a member of the A6 subclass of heat shock transcription factors, in the regulation of heat stress protection genes in Triticum aestivum (bread wheat), a poorly understood phenomenon in this crop species. Expression analysis showed that TaHsfA6f was expressed constitutively in green organs but was markedly up-regulated during heat stress. Overexpression of TaHsfA6f in transgenic wheat using a drought-inducible promoter resulted in up-regulation of heat shock proteins (HSPs) and a number of other heat stress protection genes that included some previously unknown Hsf target genes such as Golgi anti-apoptotic protein (GAAP) and the large isoform of Rubisco activase. Transgenic wheat plants overexpressing TaHsfA6f showed improved thermotolerance. Transactivation assays showed that TaHsfA6f activated the expression of reporter genes driven by the promoters of several HSP genes (TaHSP16.8, TaHSP17, TaHSP17.3, and TaHSP90.1-A1) as well as TaGAAP and TaRof1 (a co-chaperone) under non-stress conditions. DNA binding analysis revealed the presence of high-affinity TaHsfA6f-binding heat shock element-like motifs in the promoters of these six genes. Promoter truncation and mutagenesis analyses identified TaHsfA6f-binding elements that were responsible for transactivation of TaHSP90.1-A1 and TaGAAP by TaHsfA6f. These data suggest that TaHsfA6f is a transcriptional activator that directly regulates TaHSP, TaGAAP, and TaRof1 genes in wheat and its gene regulatory network has a positive impact on thermotolerance. PMID:25428996

  4. TaHsfA6f is a transcriptional activator that regulates a suite of heat stress protection genes in wheat (Triticum aestivum L.) including previously unknown Hsf targets.

    PubMed

    Xue, Gang-Ping; Drenth, Janneke; McIntyre, C Lynne

    2015-02-01

    Heat stress is a significant environmental factor adversely affecting crop yield. Crop adaptation to high-temperature environments requires transcriptional reprogramming of a suite of genes involved in heat stress protection. This study investigated the role of TaHsfA6f, a member of the A6 subclass of heat shock transcription factors, in the regulation of heat stress protection genes in Triticum aestivum (bread wheat), a poorly understood phenomenon in this crop species. Expression analysis showed that TaHsfA6f was expressed constitutively in green organs but was markedly up-regulated during heat stress. Overexpression of TaHsfA6f in transgenic wheat using a drought-inducible promoter resulted in up-regulation of heat shock proteins (HSPs) and a number of other heat stress protection genes that included some previously unknown Hsf target genes such as Golgi anti-apoptotic protein (GAAP) and the large isoform of Rubisco activase. Transgenic wheat plants overexpressing TaHsfA6f showed improved thermotolerance. Transactivation assays showed that TaHsfA6f activated the expression of reporter genes driven by the promoters of several HSP genes (TaHSP16.8, TaHSP17, TaHSP17.3, and TaHSP90.1-A1) as well as TaGAAP and TaRof1 (a co-chaperone) under non-stress conditions. DNA binding analysis revealed the presence of high-affinity TaHsfA6f-binding heat shock element-like motifs in the promoters of these six genes. Promoter truncation and mutagenesis analyses identified TaHsfA6f-binding elements that were responsible for transactivation of TaHSP90.1-A1 and TaGAAP by TaHsfA6f. These data suggest that TaHsfA6f is a transcriptional activator that directly regulates TaHSP, TaGAAP, and TaRof1 genes in wheat and its gene regulatory network has a positive impact on thermotolerance. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. Erythropoietin Levels in Elderly Patients with Anemia of Unknown Etiology

    PubMed Central

    Sriram, Swetha; Martin, Alison; Xenocostas, Anargyros; Lazo-Langner, Alejandro

    2016-01-01

    Background In many elderly patients with anemia, a specific cause cannot be identified. This study investigates whether erythropoietin levels are inappropriately low in these cases of “anemia of unknown etiology” and whether this trend persists after accounting for confounders. Methods This study includes all anemic patients over 60 years old who had erythropoietin measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient’s anemia to one of ten etiologies: chronic kidney disease, iron deficiency, chronic disease, confirmed myelodysplastic syndrome (MDS), suspected MDS, vitamin B12 deficiency, folate deficiency, anemia of unknown etiology, other etiology, or multifactorial etiology. Iron deficiency anemia served as the comparison group in all analyses. We used linear regression to model the relationship between erythropoietin and the presence of each etiology, sequentially adding terms to the model to account for the hemoglobin concentration, estimated glomerular filtration rate (eGFR) and Charlson Comorbidity Index. Results A total of 570 patients met the inclusion criteria. Linear regression analysis showed that erythropoietin levels in chronic kidney disease, anemia of chronic disease and anemia of unknown etiology were lower by 48%, 46% and 27%, respectively, compared to iron deficiency anemia even after adjusting for hemoglobin, eGFR and comorbidities. Conclusions We have shown that erythropoietin levels are inappropriately low in anemia of unknown etiology, even after adjusting for confounders. This suggests that decreased erythropoietin production may play a key role in the pathogenesis of anemia of unknown etiology. PMID:27310832

  6. Nonnegative Matrix Factorization for identification of unknown number of sources emitting delayed signals

    PubMed Central

    Iliev, Filip L.; Stanev, Valentin G.; Vesselinov, Velimir V.

    2018-01-01

    Factor analysis is broadly used as a powerful unsupervised machine learning tool for reconstruction of hidden features in recorded mixtures of signals. In the case of a linear approximation, the mixtures can be decomposed by a variety of model-free Blind Source Separation (BSS) algorithms. Most of the available BSS algorithms consider an instantaneous mixing of signals, while the case when the mixtures are linear combinations of signals with delays is less explored. Especially difficult is the case when the number of sources of the signals with delays is unknown and has to be determined from the data as well. To address this problem, in this paper, we present a new method based on Nonnegative Matrix Factorization (NMF) that is capable of identifying: (a) the unknown number of the sources, (b) the delays and speed of propagation of the signals, and (c) the locations of the sources. Our method can be used to decompose records of mixtures of signals with delays emitted by an unknown number of sources in a nondispersive medium, based only on recorded data. This is the case, for example, when electromagnetic signals from multiple antennas are received asynchronously; or mixtures of acoustic or seismic signals recorded by sensors located at different positions; or when a shift in frequency is induced by the Doppler effect. By applying our method to synthetic datasets, we demonstrate its ability to identify the unknown number of sources as well as the waveforms, the delays, and the strengths of the signals. Using Bayesian analysis, we also evaluate estimation uncertainties and identify the region of likelihood where the positions of the sources can be found. PMID:29518126

  7. Nonnegative Matrix Factorization for identification of unknown number of sources emitting delayed signals.

    PubMed

    Iliev, Filip L; Stanev, Valentin G; Vesselinov, Velimir V; Alexandrov, Boian S

    2018-01-01

    Factor analysis is broadly used as a powerful unsupervised machine learning tool for reconstruction of hidden features in recorded mixtures of signals. In the case of a linear approximation, the mixtures can be decomposed by a variety of model-free Blind Source Separation (BSS) algorithms. Most of the available BSS algorithms consider an instantaneous mixing of signals, while the case when the mixtures are linear combinations of signals with delays is less explored. Especially difficult is the case when the number of sources of the signals with delays is unknown and has to be determined from the data as well. To address this problem, in this paper, we present a new method based on Nonnegative Matrix Factorization (NMF) that is capable of identifying: (a) the unknown number of the sources, (b) the delays and speed of propagation of the signals, and (c) the locations of the sources. Our method can be used to decompose records of mixtures of signals with delays emitted by an unknown number of sources in a nondispersive medium, based only on recorded data. This is the case, for example, when electromagnetic signals from multiple antennas are received asynchronously; or mixtures of acoustic or seismic signals recorded by sensors located at different positions; or when a shift in frequency is induced by the Doppler effect. By applying our method to synthetic datasets, we demonstrate its ability to identify the unknown number of sources as well as the waveforms, the delays, and the strengths of the signals. Using Bayesian analysis, we also evaluate estimation uncertainties and identify the region of likelihood where the positions of the sources can be found.

  8. Sequence Elucidation of an Unknown Cyclic Peptide of High Doping Potential by ETD and CID Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Guan, Fuyu; Uboh, Cornelius E.; Soma, Lawrence R.; Rudy, Jeffrey

    2011-04-01

    Identification of an unknown substance without any information remains a daunting challenge despite advances in chemistry and mass spectrometry. However, an unknown cyclic peptide in a sample with very limited volume seized at a Pennsylvania racetrack has been successfully identified. The unknown sample was determined by accurate mass measurements to contain a small unknown peptide as the major component. Collision-induced dissociation (CID) of the unknown peptide revealed the presence of Lys (not Gln, by accurate mass), Phe, and Arg residues, and absence of any y-type product ion. The latter, together with the tryptic digestion results of the unusual deamidation and absence of any tryptic cleavage, suggests a cyclic structure for the peptide. Electron-transfer dissociation (ETD) of the unknown peptide indicated the presence of Gln (not Lys, by the unusual deamidation), Phe, and Arg residues and their connectivity. After all the results were pieced together, a cyclic tetrapeptide, cyclo[Arg-Lys-N(C6H9)Gln-Phe], is proposed for the unknown peptide. Observations of different amino acid residues from CID and ETD experiments for the peptide were interpreted by a fragmentation pathway proposed, as was preferential CID loss of a Lys residue from the peptide. ETD was used for the first time in sequencing of a cyclic peptide; product ions resulting from ETD of the peptide identified were categorized into two types and named pseudo-b and pseudo-z ions that are important for sequencing of cyclic peptides. The ETD product ions were interpreted by fragmentation pathways proposed. Additionally, multi-stage CID mass spectrometry cannot provide complete sequence information for cyclic peptides containing adjacent Arg and Lys residues. The identified cyclic peptide has not been documented in the literature, its pharmacological effects are unknown, but it might be a "designer" drug with athletic performance-enhancing effects.

  9. Correlates of Unknown HIV Status Among MSM Participating in the 2014 American Men's Internet Survey (AMIS).

    PubMed

    Traynor, S M; Brincks, A M; Feaster, D J

    2017-08-29

    Increasing serostatus awareness is a key HIV prevention strategy. Despite expanded testing efforts, some men who have sex with men (MSM) remain unaware of their HIV status. This study explored demographic characteristics, sexual identity, sexual role, and behavioral factors associated with unknown HIV status among MSM in the United States. Data from 9170 MSM in the 2014 American Men's Internet Survey were analyzed using logistic regression to identify correlates of unknown HIV status. Young age, race, low education, rural residence, and lack of recent healthcare visits were significantly associated with unknown HIV status. In addition, nondisclosure of one's sexual orientation (OR = 3.70, 95% CI 2.99-4.59) and a self-identified sexual role as "bottom" (OR = 1.45, 95% CI 1.24-1.70) were predictors of unknown HIV status. Post-hoc analysis showed HIV-negative MSM not tested in the last year had fewer self-reported risk behaviors than recent testers, suggesting that repeat testing among MSM may be aligned with individual risk.

  10. Neurological autoantibodies in drug-resistant epilepsy of unknown cause.

    PubMed

    Tecellioglu, Mehmet; Kamisli, Ozden; Kamisli, Suat; Yucel, Fatma Ebru; Ozcan, Cemal

    2018-03-09

    Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were determined. Serum antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive patients. Autoimmune factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

  11. Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis.

    PubMed

    Kuk, Deborah; Shoushtari, Alexander N; Barker, Christopher A; Panageas, Katherine S; Munhoz, Rodrigo R; Momtaz, Parisa; Ariyan, Charlotte E; Brady, Mary Sue; Coit, Daniel G; Bogatch, Kita; Callahan, Margaret K; Wolchok, Jedd D; Carvajal, Richard D; Postow, Michael A

    2016-07-01

    Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006-2010 and 2011-2013 had better overall survival than patients diagnosed in 2000-2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous melanoma or unknown primary melanoma. No studies, however, have been conducted assessing the

  12. Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis

    PubMed Central

    Kuk, Deborah; Shoushtari, Alexander N.; Barker, Christopher A.; Panageas, Katherine S.; Munhoz, Rodrigo R.; Momtaz, Parisa; Ariyan, Charlotte E.; Brady, Mary Sue; Coit, Daniel G.; Bogatch, Kita; Callahan, Margaret K.; Wolchok, Jedd D.; Carvajal, Richard D.

    2016-01-01

    Background. Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. Materials and Methods. We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. Results. Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006–2010 and 2011–2013 had better overall survival than patients diagnosed in 2000–2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. Conclusion. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. Implications for Practice: Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous

  13. Homozygosity Mapping Identifies a Bile Acid Biosynthetic Defect in an Adult with Cirrhosis of Unknown Etiology

    PubMed Central

    Molho-Pessach, Vered; Rios, Jonathan J.; Xing, Chao; Setchell, Kenneth D.R.; Cohen, Jonathan C.; Hobbs, Helen H.

    2013-01-01

    The most common inborn error of bile acid metabolism is 3β-hydroxy-Δ5-C27-steroid oxidoreductase (3β-HSD) deficiency, a disorder that usually presents in early childhood with hepatic dysfunction. Timely diagnosis of this disorder is crucial since it can be effectively treated with primary bile acid replacement. Here we describe a 24-year-old woman from Iran with cirrhosis of unknown etiology. Her sister and a first cousin died of cirrhosis (ages 19 and 6 years) and another 32-year old first cousin had a self-limited liver disorder in childhood that resolved at age 9 years. The family history was consistent with the notion that affected family members were homozygous for a mutant allele inherited identical-by-descent. A genome-wide analysis of 2.5 million single nucleotide polymorphisms (SNP) was performed to identify regions of homozygosity that were present in the proband and the 32-year old first cousin, but not in a healthy relative. One of these regions contained the gene encoding 3β-HSD (HSD3B7). Sequence analysis of HSD3B7 revealed that the proband and her 32-year old cousin were homozygous for a frame shift mutation (c.45_46del AG, p.T15Tfsx27) in exon 1. The diagnosis of 3β-HSD deficiency was confirmed by documenting high levels of 3β-hydroxy-Δ5 bile acids in the serum of the first cousin using mass spectrometry. To our knowledge, the 32-year old relative in this family represents the oldest asymptomatic patient with this disorder. Conclusion: This study highlights the clinical utility of homozygosity mapping in diagnosing autosomal recessive metabolic disorders. This family illustrates the wide variation in expressivity that occurs in 3β-HSD deficiency and underscores the need to consider a bile acid synthetic defect as a possible cause of liver disease in adults. PMID:22095780

  14. Previously identified patellar tendinopathy risk factors differ between elite and sub-elite volleyball players.

    PubMed

    Janssen, I; Steele, J R; Munro, B J; Brown, N A T

    2015-06-01

    Patellar tendinopathy is the most common knee injury incurred in volleyball, with its prevalence in elite athletes more than three times that of their sub-elite counterparts. The purpose of this study was to determine whether patellar tendinopathy risk factors differed between elite and sub-elite male volleyball players. Nine elite and nine sub-elite male volleyball players performed a lateral stop-jump block movement. Maximum vertical jump, training history, muscle extensibility and strength, three-dimensional landing kinematics (250 Hz), along with lower limb neuromuscular activation patterns (1500 Hz), and patellar tendon loading were collected during each trial. Multivariate analyses of variance (P < 0.05) assessed for between-group differences in risk factors or patellar tendon loading. Significant interaction effects were further evaluated using post-hoc univariate analysis of variance tests. Landing kinematics, neuromuscular activation patterns, patellar tendon loading, and most of the previously identified risk factors did not differ between the elite and sub-elite players. However, elite players participated in a higher training volume and had less quadriceps extensibility than sub-elite players. Therefore, high training volume is likely the primary contributor to the injury discrepancy between elite and sub-elite volleyball players. Interventions designed to reduce landing frequency and improve quadriceps extensibility are recommended to reduce patellar tendinopathy prevalence in volleyball players. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Molecular toolbox for the identification of unknown genetically modified organisms.

    PubMed

    Ruttink, Tom; Demeyer, Rolinde; Van Gulck, Elke; Van Droogenbroeck, Bart; Querci, Maddalena; Taverniers, Isabel; De Loose, Marc

    2010-03-01

    Competent laboratories monitor genetically modified organisms (GMOs) and products derived thereof in the food and feed chain in the framework of labeling and traceability legislation. In addition, screening is performed to detect the unauthorized presence of GMOs including asynchronously authorized GMOs or GMOs that are not officially registered for commercialization (unknown GMOs). Currently, unauthorized or unknown events are detected by screening blind samples for commonly used transgenic elements, such as p35S or t-nos. If (1) positive detection of such screening elements shows the presence of transgenic material and (2) all known GMOs are tested by event-specific methods but are not detected, then the presence of an unknown GMO is inferred. However, such evidence is indirect because it is based on negative observations and inconclusive because the procedure does not identify the causative event per se. In addition, detection of unknown events is hampered in products that also contain known authorized events. Here, we outline alternative approaches for analytical detection and GMO identification and develop new methods to complement the existing routine screening procedure. We developed a fluorescent anchor-polymerase chain reaction (PCR) method for the identification of the sequences flanking the p35S and t-nos screening elements. Thus, anchor-PCR fingerprinting allows the detection of unique discriminative signals per event. In addition, we established a collection of in silico calculated fingerprints of known events to support interpretation of experimentally generated anchor-PCR GM fingerprints of blind samples. Here, we first describe the molecular characterization of a novel GMO, which expresses recombinant human intrinsic factor in Arabidopsis thaliana. Next, we purposefully treated the novel GMO as a blind sample to simulate how the new methods lead to the molecular identification of a novel unknown event without prior knowledge of its transgene

  16. Eosinophilic pustular folliculitis: a sterile folliculitis of unknown cause?

    PubMed

    Brenner, S; Wolf, R; Ophir, J

    1994-08-01

    Eosinophilic pustular folliculitis (EPF) was initially defined as a sterile folliculitis of unknown cause. Because attempts to demonstrate bacterial organisms have been unsuccessful, and antibiotic therapy is usually ineffective, a bacterial infection is not considered a plausible causative factor for this disease. Our purpose was to describe five patients with the clinical and histologic characteristics of EPF and to report the results of bacterial cultures. Biopsy specimens were examined and pustules were cultured. In three of the five patients, Pseudomonas infection of the hair follicle was the cause of the disease as proven by repeated cultures and the response to specific therapy. Three patients had a systemic disorder known to cause immunologic alteration: AIDS in one and a myeloproliferative disorder in two. Although EPF was initially defined as a sterile folliculitis of unknown origin, three of our patients had an identifiable and treatable cause. We believe that these cases warrant the diagnosis of EPF.

  17. Comparing the Effects of Unknown-Known Ratios on Word Reading Learning versus Learning Rates

    ERIC Educational Resources Information Center

    Joseph, Laurice M.; Nist, Lindsay M.

    2006-01-01

    An extension of G. L. Cates et al. (2003) investigation was conducted to determine if students' cumulative learning rates would be superior for words read under a traditional drill and practice condition (as they were for spelling in the previous study) than under interspersal conditions of varying ratios of unknown to known words. Participants…

  18. Cost-effectiveness of using a gene expression profiling test to aid in identifying the primary tumour in patients with cancer of unknown primary.

    PubMed

    Hannouf, M B; Winquist, E; Mahmud, S M; Brackstone, M; Sarma, S; Rodrigues, G; Rogan, P; Hoch, J S; Zaric, G S

    2017-06-01

    We aimed to investigate the cost-effectiveness of a 2000-gene-expression profiling (GEP) test to help identify the primary tumor site when clinicopathological diagnostic evaluation was inconclusive in patients with cancer of unknown primary (CUP). We built a decision-analytic-model to project the lifetime clinical and economic consequences of different clinical management strategies for CUP. The model was parameterized using follow-up data from the Manitoba Cancer Registry, cost data from Manitoba Health administrative databases and secondary sources. The 2000-GEP-based strategy compared to current clinical practice resulted in an incremental cost-effectiveness ratio (ICER) of $44,151 per quality-adjusted life years (QALY) gained. The total annual-budget impact was $36.2 million per year. A value-of-information analysis revealed that the expected value of perfect information about the test's clinical impact was $4.2 million per year. The 2000-GEP test should be considered for adoption in CUP. Field evaluations of the test are associated with a large societal benefit.

  19. On Known Unknowns: Fluency and the Neural Mechanisms of Illusory Truth

    PubMed Central

    Wang, Wei-Chun; Brashier, Nadia M.; Wing, Erik A.; Marsh, Elizabeth J.; Cabeza, Roberto

    2016-01-01

    The “illusory truth” effect refers to the phenomenon whereby repetition of a statement increases its likelihood of being judged true. This phenomenon has important implications for how we come to believe oft-repeated information that may be misleading or unknown. Behavioral evidence indicates that fluency or the subjective ease experienced while processing a statement underlies this effect. This suggests that illusory truth should be mediated by brain regions previously linked to fluency, such as the perirhinal cortex (PRC). To investigate this possibility, we scanned participants with fMRI while they rated the truth of unknown statements, half of which were presented earlier (i.e., repeated). The only brain region that showed an interaction between repetition and ratings of perceived truth was PRC, where activity increased with truth ratings for repeated, but not for new, statements. This finding supports the hypothesis that illusory truth is mediated by a fluency mechanism and further strengthens the link between PRC and fluency. PMID:26765947

  20. Lack of in vitro constitutive activity for four previously reported TSH receptor mutations identified in patients with nonautoimmune hyperthyroidism and hot thyroid carcinomas.

    PubMed

    Jaeschke, Holger; Mueller, Sandra; Eszlinger, Markus; Paschke, Ralf

    2010-12-01

    Constitutively activating mutations (CAMs) of the TSHR are the major cause for nonautoimmune hyperthyroidism. Re-examination of constitutive activity previously determined in CHO cell lines recently demonstrated the caveats for the in vitro determination of constitutive TSHR activity, which leads to false positive conclusions regarding the molecular origin of hyperthyroidism or hot thyroid carcinomas. Mutations L677V and T620I identified in hot thyroid carcinomas were previously characterized in CHO and in 3T3-Vill cell lines, respectively, stably expressing the mutant without determination of TSHR expression. F666L identified in a patient with hot thyroid nodules, I691F in a family with nonautoimmune hyperthyroidism and F631I identified in a hot thyroid carcinoma were not characterized for their in vitro function. Therefore, we decided to (re)evaluate the in vitro function of these five TSHR variants by determination of cell surface expression, and intracellular cAMP and inositol phosphate levels and performed additionally linear regression analyses to determine basal activity independently from the mutant's cell surface expression in COS-7 and HEK(GT) cells. Only one (F631I) of the five investigated TSHR variants displayed constitutive activity for G(α) s signalling and showed correlation with the clinical phenotype. The previous false classification of T620I and L677V as CAMs is most likely related to the fact that both mutations were characterized in cell lines stably expressing the mutated receptor construct without assessing the respective receptor number per cell. Other molecular aetiologies for the nonautoimmune hyperthyroidism and/or hot thyroid carcinomas in these three patients and one family should be elucidated. © 2010 Blackwell Publishing Ltd.

  1. Carcinoma of Unknown Primary—Patient Version

    Cancer.gov

    Carcinoma of unknown primary (CUP) occurs when cancer cells have spread in the body and formed metastatic tumors but the site of the primary cancer is not known. There are a number of reasons why the primary cancer may not be found. Start here to find treatment information for carcinoma of unknown primary.

  2. Identifying unknown by-products in drinking water using comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry and in silico toxicity assessment.

    PubMed

    Li, Chunmei; Wang, Donghong; Li, Na; Luo, Qian; Xu, Xiong; Wang, Zijian

    2016-11-01

    Improvements in extraction and detection technologies have increased our abilities to identify new disinfection by-products (DBPs) over the last 40 years. However, most previous studies combined DBP identification and measurement efforts with toxicology to address concerns on a few expected DBPs, making it difficult to better define the health risk from the individual DBPs. In this study, a nontargeted screening method involving comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry (GC × GC-qMS) combined with OECD QSAR Toolbox Ver. 3.2 was developed for identifying and prioritizing of volatile and semi-volatile DBPs in drinking water. The method was successfully applied to analyze DBPs formed during chlorination, chloramination or ozonation of the raw water. Over 500 compounds were tentatively identified in each sample, showing the superior performance of this analytical technique. A total of 170 volatile and semi-volatile DBPs representing fourteen chemical classes were then identified, according to the criteria that the DBP was presented in the duplicate treated samples. The genotoxicity and carcinogenicity of the DBPs were evaluated using Toolbox, and 58 DBPs were found to be actual or potential genotoxicants. The accuracy of the compound identification was determined by comparing 47 identified compounds with commercially available standards. About 90% (41 of the 47) of the compounds that were automatically identified using the library were correct. The results show that GC×GC-qMS coupled with a quantitative structure-activity relationship model is a powerful and fast nontargeted screening technique for compounds. The method and results provide us a new idea for identification and prioritization of DBPs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation

    PubMed Central

    Nollen, Ellen A. A.; Garcia, Susana M.; van Haaften, Gijs; Kim, Soojin; Chavez, Alejandro; Morimoto, Richard I.; Plasterk, Ronald H. A.

    2004-01-01

    Protein misfolding and the formation of aggregates are increasingly recognized components of the pathology of human genetic disease and hallmarks of many neurodegenerative disorders. As exemplified by polyglutamine diseases, the propensity for protein misfolding is associated with the length of polyglutamine expansions and age-dependent changes in protein-folding homeostasis, suggesting a critical role for a protein homeostatic buffer. To identify the complement of protein factors that protects cells against the formation of protein aggregates, we tested transgenic Caenorhabditis elegans strains expressing polyglutamine expansion yellow fluorescent protein fusion proteins at the threshold length associated with the age-dependent appearance of protein aggregation. We used genome-wide RNA interference to identify genes that, when suppressed, resulted in the premature appearance of protein aggregates. Our screen identified 186 genes corresponding to five principal classes of polyglutamine regulators: genes involved in RNA metabolism, protein synthesis, protein folding, and protein degradation; and those involved in protein trafficking. We propose that each of these classes represents a molecular machine collectively comprising the protein homeostatic buffer that responds to the expression of damaged proteins to prevent their misfolding and aggregation. PMID:15084750

  4. Identification of "Known Unknowns" Utilizing Accurate Mass Data and ChemSpider

    NASA Astrophysics Data System (ADS)

    Little, James L.; Williams, Antony J.; Pshenichnov, Alexey; Tkachenko, Valery

    2012-01-01

    In many cases, an unknown to an investigator is actually known in the chemical literature, a reference database, or an internet resource. We refer to these types of compounds as "known unknowns." ChemSpider is a very valuable internet database of known compounds useful in the identification of these types of compounds in commercial, environmental, forensic, and natural product samples. The database contains over 26 million entries from hundreds of data sources and is provided as a free resource to the community. Accurate mass mass spectrometry data is used to query the database by either elemental composition or a monoisotopic mass. Searching by elemental composition is the preferred approach. However, it is often difficult to determine a unique elemental composition for compounds with molecular weights greater than 600 Da. In these cases, searching by the monoisotopic mass is advantageous. In either case, the search results are refined by sorting the number of references associated with each compound in descending order. This raises the most useful candidates to the top of the list for further evaluation. These approaches were shown to be successful in identifying "known unknowns" noted in our laboratory and for compounds of interest to others.

  5. Identifying chemicals that are planetary boundary threats.

    PubMed

    MacLeod, Matthew; Breitholtz, Magnus; Cousins, Ian T; de Wit, Cynthia A; Persson, Linn M; Rudén, Christina; McLachlan, Michael S

    2014-10-07

    Rockström et al. proposed a set of planetary boundaries that delimit a "safe operating space for humanity". Many of the planetary boundaries that have so far been identified are determined by chemical agents. Other chemical pollution-related planetary boundaries likely exist, but are currently unknown. A chemical poses an unknown planetary boundary threat if it simultaneously fulfills three conditions: (1) it has an unknown disruptive effect on a vital Earth system process; (2) the disruptive effect is not discovered until it is a problem at the global scale, and (3) the effect is not readily reversible. In this paper, we outline scenarios in which chemicals could fulfill each of the three conditions, then use the scenarios as the basis to define chemical profiles that fit each scenario. The chemical profiles are defined in terms of the nature of the effect of the chemical and the nature of exposure of the environment to the chemical. Prioritization of chemicals in commerce against some of the profiles appears feasible, but there are considerable uncertainties and scientific challenges that must be addressed. Most challenging is prioritizing chemicals for their potential to have a currently unknown effect on a vital Earth system process. We conclude that the most effective strategy currently available to identify chemicals that are planetary boundary threats is prioritization against profiles defined in terms of environmental exposure combined with monitoring and study of the biogeochemical processes that underlie vital Earth system processes to identify currently unknown disruptive effects.

  6. Existence conditions for unknown input functional observers

    NASA Astrophysics Data System (ADS)

    Fernando, T.; MacDougall, S.; Sreeram, V.; Trinh, H.

    2013-01-01

    This article presents necessary and sufficient conditions for the existence and design of an unknown input Functional observer. The existence of the observer can be verified by computing a nullspace of a known matrix and testing some matrix rank conditions. The existence of the observer does not require the satisfaction of the observer matching condition (i.e. Equation (16) in Hou and Muller 1992, 'Design of Observers for Linear Systems with Unknown Inputs', IEEE Transactions on Automatic Control, 37, 871-875), is not limited to estimating scalar functionals and allows for arbitrary pole placement. The proposed observer always exists when a state observer exists for the unknown input system, and furthermore, the proposed observer can exist even in some instances when an unknown input state observer does not exist.

  7. Structural Identifiability of Dynamic Systems Biology Models

    PubMed Central

    Villaverde, Alejandro F.

    2016-01-01

    A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areas. PMID:27792726

  8. A novel HPLC-MRM strategy to discover unknown and long-term metabolites of stanozolol for expanding analytical possibilities in doping-control.

    PubMed

    Wang, Zhe; Zhou, Xinmiao; Liu, Xin; Dong, Ying; Zhang, Jinlan

    2017-01-01

    Stanozolol is one of the most commonly abused anabolic androgenic steroids (AAS) by athletes and usually detected by its parent drug and major metabolites. However, its metabolic pathway is complex, varied and individually different, it is important to characterize its overall metabolic profiles and discover new and long-term metabolites for the aims of expanding detection windows. High performance liquid chromatography coupled with triple quadrupole mass spectrometer (HPLC-MS/MS) was used to analyze the human urine after oral administration of stanozolol. Multiple reaction monitoring (MRM), one of the scan modes of triple quadrupole mass spectrometer showing extremely high sensitivity was well used to develop a strategy for metabolic profiles characterization and long-term metabolites detection based on typical precursor to product ion transitions of parent drug and its major metabolites. Utilizing the characteristic fragment ions of stanozolol and its major metabolites as the product ions, and speculating unknown precursor ions based on the possible phase I and phase II metabolic reactions in human body, the metabolite profiles of stanozolol could be comprehensively discovered, especially for those unknown and low concentration metabolites in human urine. Then these metabolites were further well structure identified by targeted high resolution MS/MS scan of quadrupole-time of flight mass spectrometry (Q-TOF). Applying this strategy, 27 phase I and 21 phase II metabolites of stanozolol were identified, in which 13 phase I and 14 phase II metabolites have not been reported previously. The 9 out of 48 metabolites could be detected over 15days post drug administration. This strategy could be employed effectively to characterize AAS metabolic profiles and discover unknown and long-term metabolites in sports drug testing. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Top-Down Proteomics and Direct Surface Sampling of Neonatal Dried Blood Spots: Diagnosis of Unknown Hemoglobin Variants

    NASA Astrophysics Data System (ADS)

    Edwards, Rebecca L.; Griffiths, Paul; Bunch, Josephine; Cooper, Helen J.

    2012-11-01

    We have previously shown that liquid microjunction surface sampling of dried blood spots coupled with high resolution top-down mass spectrometry may be used for screening of common hemoglobin variants HbS, HbC, and HbD. In order to test the robustness of the approach, we have applied the approach to unknown hemoglobin variants. Six neonatal dried blood spot samples that had been identified as variants, but which could not be diagnosed by current screening methods, were analyzed by direct surface sampling top-down mass spectrometry. Both collision-induced dissociation and electron transfer dissociation mass spectrometry were employed. Four of the samples were identified as β-chain variants: two were heterozygous Hb D-Iran, one was heterozygous Hb Headington, and one was heterozygous Hb J-Baltimore. The fifth sample was identified as the α-chain variant heterozygous Hb Phnom Penh. Analysis of the sixth sample suggested that it did not in fact contain a variant. Adoption of the approach in the clinic would require speed in both data collection and interpretation. To address that issue, we have compared manual data analysis with freely available data analysis software (ProsightPTM). The results demonstrate the power of top-down proteomics for hemoglobin variant analysis in newborn samples.

  10. Ranging algebraically with more observations than unknowns

    NASA Astrophysics Data System (ADS)

    Awange, J. L.; Fukuda, Y.; Takemoto, S.; Ateya, I. L.; Grafarend, E. W.

    2003-07-01

    In the recently developed Spatial Reference System that is designed to check and control the accuracy of the three-dimensional coordinate measuring machines and tooling equipment (Metronom US., Inc., Ann Arbor: http://www.metronomus.com), the coordinates of the edges of the instrument are computed from distances of the bars. The use of distances in industrial application is fast gaining momentum just as in Geodesy and in Geophysical applications and thus necessitating efficient algorithms to solve the nonlinear distance equations. Whereas the ranging problem with minimum known stations was considered in our previous contribution in the same Journal, the present contribution extends to the case where one is faced with many distance observations than unknowns (overdetermined case) as is usually the case in practise. Using the Gauss-Jacobi Combinatorial approach, we demonstrate how one can proceed to position without reverting to iterative and linearizing procedures such as Newton's or Least Squares approach.

  11. Analyzing recurrent events when the history of previous episodes is unknown or not taken into account: proceed with caution.

    PubMed

    Navarro, Albert; Casanovas, Georgina; Alvarado, Sergio; Moriña, David

    Researchers in public health are often interested in examining the effect of several exposures on the incidence of a recurrent event. The aim of the present study is to assess how well the common-baseline hazard models perform to estimate the effect of multiple exposures on the hazard of presenting an episode of a recurrent event, in presence of event dependence and when the history of prior-episodes is unknown or is not taken into account. Through a comprehensive simulation study, using specific-baseline hazard models as the reference, we evaluate the performance of common-baseline hazard models by means of several criteria: bias, mean squared error, coverage, confidence intervals mean length and compliance with the assumption of proportional hazards. Results indicate that the bias worsen as event dependence increases, leading to a considerable overestimation of the exposure effect; coverage levels and compliance with the proportional hazards assumption are low or extremely low, worsening with increasing event dependence, effects to be estimated, and sample sizes. Common-baseline hazard models cannot be recommended when we analyse recurrent events in the presence of event dependence. It is important to have access to the history of prior-episodes per subject, it can permit to obtain better estimations of the effects of the exposures. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Lesser devil rays Mobula cf. hypostoma from Venezuela are almost twice their previously reported maximum size and may be a new sub-species.

    PubMed

    Ehemann, N R; González-González, L V; Trites, A W

    2017-03-01

    Three rays opportunistically obtained near Margarita Island, Venezuela, were identified as lesser devil rays Mobula cf. hypostoma, but their disc widths were between 207 and 230 cm, which is almost double the reported maximum disc width of 120 cm for this species. These morphometric data suggest that lesser devil rays are either larger than previously recognized or that these specimens belong to an unknown sub-species of Mobula in the Caribbean Sea. Better data are needed to describe the distribution, phenotypic variation and population structure of this poorly known species. © 2017 The Fisheries Society of the British Isles.

  13. Natural History of Ground-Glass Lesions Among Patients With Previous Lung Cancer.

    PubMed

    Shewale, Jitesh B; Nelson, David B; Rice, David C; Sepesi, Boris; Hofstetter, Wayne L; Mehran, Reza J; Vaporciyan, Ara A; Walsh, Garrett L; Swisher, Stephen G; Roth, Jack A; Antonoff, Mara B

    2018-06-01

    Among patients with previous lung cancer, the malignant potential of subsequent ground-glass opacities (GGOs) on computed tomography remains unknown, with a lack of consensus regarding surveillance and intervention. This study sought to describe the natural history of GGO in patients with a history of lung cancer. A retrospective review was performed of 210 patients with a history of lung cancer and ensuing computed tomography evidence of pure or mixed GGOs between 2007 and 2013. Computed tomography reports were reviewed to determine the fate of the GGOs, by classifying all lesions as stable, resolved, or progressive over the course of the study. Multivariable analysis was performed to identify predictors of GGO progression and resolution. The mean follow-up time was 13 months. During this period, 55 (26%) patients' GGOs were stable, 131 (62%) resolved, and 24 (11%) progressed. Of the 24 GGOs that progressed, three were subsequently diagnosed as adenocarcinoma. Patients of black race (odds ratio [OR], 0.26) and other races besides white (OR, 0.89) had smaller odds of GGO resolution (p = 0.033), whereas patients with previous lung squamous cell carcinoma (OR, 5.16) or small cell carcinoma (OR, 5.36) were more likely to experience GGO resolution (p < 0.001). On multivariable analysis, only a history of adenocarcinoma was an independent predictor of GGO progression (OR, 6.9; p = 0.011). Among patients with a history of lung cancer, prior adenocarcinoma emerged as a predictor of GGO progression, whereas a history of squamous cell carcinoma or small cell carcinoma and white race were identified as predictors of GGO resolution. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Backscattering spectrometry device for identifying unknown elements present in a workpiece

    DOEpatents

    Doyle, Barney L.; Knapp, James A.

    1991-01-01

    A backscattering spectrometry method and device for identifying and quantifying impurities in a workpiece during processing and manufacturing of that workpiece. While the workpiece is implanted with an ion beam, that same ion beam backscatters resulting from collisions with known atoms and with impurities within the workpiece. Those ions backscatter along a predetermined scattering angle and are filtered using a self-supporting filter to stop the ions with a lower energy because they collided with the known atoms of the workpiece of a smaller mass. Those ions which pass through the filter have a greater energy resulting from impact with impurities having a greater mass than the known atoms of the workpiece. A detector counts the number and measures the energy of the ions which pass through the filter. From the energy determination and knowledge of the scattering angle, a mass calculation determines the identity, and from the number and solid angle of the scattering angle, a relative concentration of the impurity is obtained.

  15. Adaptive neural control for a class of nonlinear time-varying delay systems with unknown hysteresis.

    PubMed

    Liu, Zhi; Lai, Guanyu; Zhang, Yun; Chen, Xin; Chen, Chun Lung Philip

    2014-12-01

    This paper investigates the fusion of unknown direction hysteresis model with adaptive neural control techniques in face of time-delayed continuous time nonlinear systems without strict-feedback form. Compared with previous works on the hysteresis phenomenon, the direction of the modified Bouc-Wen hysteresis model investigated in the literature is unknown. To reduce the computation burden in adaptation mechanism, an optimized adaptation method is successfully applied to the control design. Based on the Lyapunov-Krasovskii method, two neural-network-based adaptive control algorithms are constructed to guarantee that all the system states and adaptive parameters remain bounded, and the tracking error converges to an adjustable neighborhood of the origin. In final, some numerical examples are provided to validate the effectiveness of the proposed control methods.

  16. Carcinoma of Unknown Primary—Health Professional Version

    Cancer.gov

    Carcinoma of unknown primary (CUP) is a rare disease in which malignant cells are found in the body but the site of the primary cancer is not known. Most CUPs are adenocarcinomas, or undifferentiated tumors. Find evidence-based information on the treatment for carcinoma of unknown primary.

  17. 37 CFR 260.7 - Unknown copyright owners.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Unknown copyright owners. 260.7 Section 260.7 Patents, Trademarks, and Copyrights U.S. COPYRIGHT OFFICE, LIBRARY OF CONGRESS... SERVICES' DIGITAL TRANSMISSIONS OF SOUND RECORDINGS AND MAKING OF EPHEMERAL PHONORECORDS § 260.7 Unknown...

  18. Prevalence and Impact of Unknown Diabetes in the ICU.

    PubMed

    Carpenter, David L; Gregg, Sara R; Xu, Kejun; Buchman, Timothy G; Coopersmith, Craig M

    2015-12-01

    mortality (13.8% vs 11.4%; p = 0.01). Patients with unknown diabetes represent a significant percentage of ICU admissions. Measurement of hemoglobin A1c at admission can prospectively identify a population that are not known to have diabetes but have significant challenges in glycemic control in the ICU.

  19. Global Learning Spectral Archive- A new Way to deal with Unknown Urban Spectra -

    NASA Astrophysics Data System (ADS)

    Jilge, M.; Heiden, U.; Habermeyer, M.; Jürgens, C.

    2015-12-01

    Rapid urbanization processes and the need of identifying urban materials demand urban planners and the remote sensing community since years. Urban planners cannot overcome the issue of up-to-date information of urban materials due to time-intensive fieldwork. Hyperspectral remote sensing can facilitate this issue by interpreting spectral signals to provide information of occurring materials. However, the complexity of urban areas and the occurrence of diverse urban materials vary due to regional and cultural aspects as well as the size of a city, which makes identification of surface materials a challenging analysis task. For the various surface material identification approaches, spectral libraries containing pure material spectra are commonly used, which are derived from field, laboratory or the hyperspectral image itself. One of the requirements for successful image analysis is that all spectrally different surface materials are represented by the library. Currently, a universal library, applicable in every urban area worldwide and taking each spectral variability into account, is and will not be existent. In this study, the issue of unknown surface material spectra and the demand of an urban site-specific spectral library is tackled by the development of a learning spectral archive tool. Starting with an incomplete library of labelled image spectra from several German cities, surface materials of pure image pixels will be identified in a hyperspectral image based on a similarity measure (e.g. SID-SAM). Additionally, unknown image spectra of urban objects are identified based on an object- and spectral-based-rule set. The detected unknown surface material spectra are entered with additional metadata, such as regional occurrence into the existing spectral library and thus, are reusable for further studies. Our approach is suitable for pure surface material detection of urban hyperspectral images that is globally applicable by taking incompleteness into account

  20. [Reconstructive investigations and identification measures in unknown soldiers of the Second World War].

    PubMed

    Jopp-van Well, Eilin; Gehl, Axel; Säring, Dennis; Amling, Michael; Hahn, Michael; Sperhake, Jan; Augustin, Christa; Krebs, Oliver; Püschel, Klaus

    2016-01-01

    The article reports on the exhumation and identification of unknown soldiers from the Second World War. With the help of medicolegal investigation and reconstruction methods an American pilot presumably murdered by a shot to the head (lynch law) and an interned Italian soldier could be identified after about 70 years and brought back home.

  1. Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy of unknown location.

    PubMed

    Insogna, Iris G; Farland, Leslie V; Missmer, Stacey A; Ginsburg, Elizabeth S; Brady, Paula C

    2017-08-01

    Pregnancies of unknown location with abnormal beta-human chorionic gonadotropin trends are frequently treated as presumed ectopic pregnancies with methotrexate. Preliminary data suggest that outpatient endometrial aspiration may be an effective tool to diagnose pregnancy location, while also sparing women exposure to methotrexate. The purpose of this study was to evaluate the utility of an endometrial sampling protocol for the diagnosis of pregnancies of unknown location after in vitro fertilization. A retrospective cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles from October 2007 to September 2015 was performed; 110 patients were diagnosed with pregnancy of unknown location, defined as a positive beta-human chorionic gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and an abnormal beta-human chorionic gonadotropin trend (<53% rise or <15% fall in 2 days). These patients underwent outpatient endometrial sampling with Karman cannula aspiration. Patients with a beta-human chorionic gonadotropin decline ≥15% within 24 hours of sampling and/or villi detected on pathologic analysis were diagnosed with failing intrauterine pregnancy and had weekly beta-human chorionic gonadotropin measurements thereafter. Those patients with beta-human chorionic gonadotropin declines <15% and no villi identified were diagnosed with ectopic pregnancy and treated with intramuscular methotrexate (50 mg/m 2 ) or laparoscopy. Across 8 years of follow up, among women with pregnancy of unknown location, failed intrauterine pregnancy was diagnosed in 46 patients (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical variables that included fresh or frozen embryo transfer, day of embryo transfer, serum beta-human chorionic gonadotropin at the time of sampling, endometrial thickness, and presence of an adnexal mass were not significantly different between patients with failed intrauterine pregnancy or ectopic

  2. Unknown components of the plastidial permeome

    PubMed Central

    Pick, Thea R.; Weber, Andreas P. M.

    2014-01-01

    Beyond their role in photosynthesis plastids provide a plethora of additional metabolic functions to plant cells. For example, they harbor complete biosynthetic pathways for the de novo synthesis of carotenoids, fatty acids, and amino acids. Furthermore plastids contribute important reactions to multi-compartmentalized pathways, such as photorespiration or plant hormone syntheses, and they depend on the import of essential molecules that they cannot synthesize themselves, such as ascorbic acid. This causes a high traffic of metabolites across the plastid envelope. Although it was recently shown that non-polar substrates could be exchanged between the plastid and the ER without involving transporters, various essential transport processes are mediated by highly selective but still unknown metabolite transporters. This review focuses on selected components of the plastidial permeome that are predicted to exist but that have not yet been identified as molecular entities, such as the transporters for isopentenyl diphosphate (IPP) or ascorbic acid. PMID:25191333

  3. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

    PubMed Central

    Gasse, Barbara; Prasad, Megana; Delgado, Sidney; Huckert, Mathilde; Kawczynski, Marzena; Garret-Bernardin, Annelyse; Lopez-Cazaux, Serena; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Stoetzel, Corinne; Bloch-Zupan, Agnès; Sire, Jean-Yves

    2017-01-01

    Amelogenesis imperfecta (AI) designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20) produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI. PMID:28659819

  4. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta.

    PubMed

    Gasse, Barbara; Prasad, Megana; Delgado, Sidney; Huckert, Mathilde; Kawczynski, Marzena; Garret-Bernardin, Annelyse; Lopez-Cazaux, Serena; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Stoetzel, Corinne; Bloch-Zupan, Agnès; Sire, Jean-Yves

    2017-01-01

    Amelogenesis imperfecta (AI) designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene ( MMP20 ) produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI.

  5. Bayesian methods for characterizing unknown parameters of material models

    DOE PAGES

    Emery, J. M.; Grigoriu, M. D.; Field Jr., R. V.

    2016-02-04

    A Bayesian framework is developed for characterizing the unknown parameters of probabilistic models for material properties. In this framework, the unknown parameters are viewed as random and described by their posterior distributions obtained from prior information and measurements of quantities of interest that are observable and depend on the unknown parameters. The proposed Bayesian method is applied to characterize an unknown spatial correlation of the conductivity field in the definition of a stochastic transport equation and to solve this equation by Monte Carlo simulation and stochastic reduced order models (SROMs). As a result, the Bayesian method is also employed tomore » characterize unknown parameters of material properties for laser welds from measurements of peak forces sustained by these welds.« less

  6. Bayesian methods for characterizing unknown parameters of material models

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

    Emery, J. M.; Grigoriu, M. D.; Field Jr., R. V.

    A Bayesian framework is developed for characterizing the unknown parameters of probabilistic models for material properties. In this framework, the unknown parameters are viewed as random and described by their posterior distributions obtained from prior information and measurements of quantities of interest that are observable and depend on the unknown parameters. The proposed Bayesian method is applied to characterize an unknown spatial correlation of the conductivity field in the definition of a stochastic transport equation and to solve this equation by Monte Carlo simulation and stochastic reduced order models (SROMs). As a result, the Bayesian method is also employed tomore » characterize unknown parameters of material properties for laser welds from measurements of peak forces sustained by these welds.« less

  7. An Alternative to the Physiological Psychology Laboratory: Identification of an Unknown Drug Through Behavioral Testing.

    ERIC Educational Resources Information Center

    Schumacher, Susan J.

    1982-01-01

    A laboratory project introduced physiological psychology students to research by requiring them to identify an unknown drug given to laboratory animals. Students read material about drugs and animal drug studies, designed behavioral tests, constructed the testing apparatus, conducted the tests, and wrote progress reports. (SR)

  8. Prevalence of unsafe sex with one's steady partner either HIV-negative or of unknown HIV status and associated determinants in Cameroon (EVAL ANRS12-116 survey).

    PubMed

    Dia, Aïssata; Marcellin, Fabienne; Bonono, Renée-Cécile; Boyer, Sylvie; Bouhnik, Anne-Déborah; Protopopescu, Camelia; Koulla-Shiro, Sinata; Carrieri, Maria Patrizia; Abé, Claude; Spire, Bruno

    2010-04-01

    Our study aimed at estimating the prevalence of inconsistent condom use and at identifying its determinants in steady partnerships among people living with HIV/AIDS (PLWHA) in Cameroon. Analyses were based on data collected during the national cross-sectional multicentre survey EVAL (ANRS 12-116), which was conducted in Cameroon between September 2006 and March 2007 among 3151 adult PLWHA diagnosed HIV-positive for at least 3 months. The study population consisted of the 907 survey participants who reported sexual activity during the previous 3 months, with a steady partner either HIV-negative or of unknown HIV status. Logistic regression was used to identify factors associated with individuals' report of inconsistent condom use during the previous 3 months. Inconsistent condom use was reported by 35.3% of sexually active PLWHA. In a multivariate analysis adjusted for socio-demographic characteristics, not receiving antiretroviral therapy (OR (95% CI): 2.28 (1.64 to 3.18)) was independently associated with inconsistent condom use. The prevalence of unsafe sex remains high among sexually active PLWHA in Cameroon. Treatment with antiretroviral therapy is identified as a factor associated with safer sex, which further encourages the continuation of the national policy for increasing access to HIV treatment and care, and underlines the need to develop counselling strategies for all patients.

  9. Cytologic regression in women with atypical squamous cells of unknown significance and negative human papillomavirus test.

    PubMed

    Wang, Shu; Lang, Jing He; Cheng, Xue Mei

    2009-12-01

    The aim of this study was to investigate the cytologic regression in women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus test. The 45 women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus at baseline were analyzed about the cytologic regression during 2 years of follow-up. The cumulative rate of cytologic regression was calculated by Kaplan-Meier curves. Of 45 women, the cumulative rates were as follows: 55.6% obtained cytologic regression before 6 months, 84.4% by 1 year, and 95.6% at 2 years. Cytologic regression was not influenced by age, menopausal status, and baseline human papillomavirus load. However, the 1-year cumulative regression rate in women with previous cervical lesions was significantly lower than those without (P=.02), even much lower in women with high-grade intraepithelial neoplasia or worse (P=.008). Most women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus could obtain cytologic regression within 2 years. Women with antecedent cervical lesions need longer time to reach this regression.

  10. Does previous use affect litter box appeal in multi-cat households?

    PubMed

    Ellis, J J; McGowan, R T S; Martin, F

    2017-08-01

    It is commonly assumed that cats actively avoid eliminated materials (especially in multi-cat homes), suggesting regular litter box cleaning as the best defense against out-of-box elimination. The relationship between previous use and litter box appeal to familiar subsequent users is currently unknown. The purpose of this study was to investigate the relationship between previous litter box use and the identity of the previous user, type of elimination, odor, and presence of physical/visual obstructions in a multi-cat household scenario. Cats preferred a clean litter box to a dirty one, but the identity of the previous user had no impact on preferences. While the presence of odor from urine and/or feces did not impact litter box preferences, the presence of odorless faux-urine and/or feces did - with the presence of faux-feces being preferred over faux-urine. Results suggest neither malodor nor chemical communication play a role in litter box preferences, and instead emphasize the importance of regular removal of physical/visual obstructions as the key factor in promoting proper litter box use. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study.

    PubMed

    Naito, Toshio; Mizooka, Masafumi; Mitsumoto, Fujiko; Kanazawa, Kenji; Torikai, Keito; Ohno, Shiro; Morita, Hiroyuki; Ukimura, Akira; Mishima, Nobuhiko; Otsuka, Fumio; Ohyama, Yoshio; Nara, Noriko; Murakami, Kazunari; Mashiba, Kouichi; Akazawa, Kenichiro; Yamamoto, Koji; Senda, Shoichi; Yamanouchi, Masashi; Tazuma, Susumu; Hayashi, Jun

    2013-12-20

    Fever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO. A nationwide retrospective study. 17 hospitals affiliated with the Japanese Society of Hospital General Medicine. This study included patients ≥18 years diagnosed with 'classical fever of unknown origin' (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011. A total of 121 patients with FUO were enrolled. The median age was 59 years (range 19-94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients. With the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO.

  12. Adaptive fuzzy prescribed performance control for MIMO nonlinear systems with unknown control direction and unknown dead-zone inputs.

    PubMed

    Shi, Wuxi; Luo, Rui; Li, Baoquan

    2017-01-01

    In this study, an adaptive fuzzy prescribed performance control approach is developed for a class of uncertain multi-input and multi-output (MIMO) nonlinear systems with unknown control direction and unknown dead-zone inputs. The properties of symmetric matrix are exploited to design adaptive fuzzy prescribed performance controller, and a Nussbaum-type function is incorporated in the controller to estimate the unknown control direction. This method has two prominent advantages: it does not require the priori knowledge of control direction and only three parameters need to be updated on-line for this MIMO systems. It is proved that all the signals in the resulting closed-loop system are bounded and that the tracking errors converge to a small residual set with the prescribed performance bounds. The effectiveness of the proposed approach is validated by simulation results. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  13. Estimating unknown input parameters when implementing the NGA ground-motion prediction equations in engineering practice

    USGS Publications Warehouse

    Kaklamanos, James; Baise, Laurie G.; Boore, David M.

    2011-01-01

    The ground-motion prediction equations (GMPEs) developed as part of the Next Generation Attenuation of Ground Motions (NGA-West) project in 2008 are becoming widely used in seismic hazard analyses. However, these new models are considerably more complicated than previous GMPEs, and they require several more input parameters. When employing the NGA models, users routinely face situations in which some of the required input parameters are unknown. In this paper, we present a framework for estimating the unknown source, path, and site parameters when implementing the NGA models in engineering practice, and we derive geometrically-based equations relating the three distance measures found in the NGA models. Our intent is for the content of this paper not only to make the NGA models more accessible, but also to help with the implementation of other present or future GMPEs.

  14. Characterization of Proteoforms with Unknown Post-translational Modifications Using the MIScore

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

    Kou, Qiang; Zhu, Binhai; Wu, Si

    Various proteoforms may be generated from a single gene due to primary structure alterations (PSAs) such as genetic variations, alternative splicing, and post-translational modifications (PTMs). Top-down mass spectrometry is capable of analyzing intact proteins and identifying patterns of multiple PSAs, making it the method of choice for studying complex proteoforms. In top-down proteomics, proteoform identification is often performed by searching tandem mass spectra against a protein sequence database that contains only one reference protein sequence for each gene or transcript variant in a proteome. Because of the incompleteness of the protein database, an identified proteoform may contain unknown PSAs comparedmore » with the reference sequence. Proteoform characterization is to identify and localize PSAs in a proteoform. Although many software tools have been proposed for proteoform identification by top-down mass spectrometry, the characterization of proteoforms in identified proteoform-spectrum matches still relies mainly on manual annotation. We propose to use the Modification Identification Score (MIScore), which is based on Bayesian models, to automatically identify and localize PTMs in proteoforms. Experiments showed that the MIScore is accurate in identifying and localizing one or two modifications.« less

  15. Learning Unknown Event Models

    DTIC Science & Technology

    2014-07-01

    Intelligence (www.aaai.org). All rights reserved. knowledge engineering, but it is often impractical due to high environment variance, or unknown events...distribution unlimited 13. SUPPLEMENTARY NOTES In Proceedings of the Twenty-Eighth AAAI Conference on Artificial Intelligence , 27-31 July 2014...autonomy for responding to unexpected events in strategy simulations. Computational Intelligence , 29(2), 187-206. Leake, D. B. (1991), Goal-based

  16. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.

    PubMed

    Bigham, Abigail; Bauchet, Marc; Pinto, Dalila; Mao, Xianyun; Akey, Joshua M; Mei, Rui; Scherer, Stephen W; Julian, Colleen G; Wilson, Megan J; López Herráez, David; Brutsaert, Tom; Parra, Esteban J; Moore, Lorna G; Shriver, Mark D

    2010-09-09

    High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary

  17. Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

    PubMed Central

    Bigham, Abigail; Bauchet, Marc; Pinto, Dalila; Mao, Xianyun; Akey, Joshua M.; Mei, Rui; Scherer, Stephen W.; Julian, Colleen G.; Wilson, Megan J.; López Herráez, David; Brutsaert, Tom; Parra, Esteban J.; Moore, Lorna G.; Shriver, Mark D.

    2010-01-01

    High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary

  18. Long-term outcome of peroral endoscopic myotomy for esophageal achalasia in patients with previous Heller myotomy.

    PubMed

    Kristensen, Helle Ø; Kirkegård, Jakob; Kjær, Daniel Willy; Mortensen, Frank Viborg; Kunda, Rastislav; Bjerregaard, Niels Christian

    2017-06-01

    Peroral endoscopic myotomy (POEM) is an emerging procedure in the treatment of esophageal achalasia, a primary motility disorder. However, the long-term outcome of POEM in patients, who have previously undergone a Heller myotomy, is unknown. Using a local database, we identified patients with esophageal achalasia, who underwent POEM. We compared patients with a previous Heller myotomy to those, who had received none or only non-surgical therapy prior to the POEM procedure. We conducted follow-up examinations at 3, 12, and 24 months following the procedure. We included 66 consecutive patients undergoing POEM for achalasia, of which 14 (21.2 %) had undergone a prior Heller myotomy. In both groups, the preoperative Eckardt score was 7. Postoperatively, the non-Heller group experienced a more pronounced symptom relief at both 3-, 12-, and 24-month follow-up compared with the Heller group, and there was a tendency for the effect of POEM to reduce over time. We suggest that there is a correlation between preoperative measurements of gastroesophageal sphincter pressures and the chance of a successful POEM. POEM has a place in the treatment of esophageal achalasia in patients with a prior Heller myotomy and persistent symptoms as it is a safe procedure with acceptable long-term results.

  19. GLRT-based array receivers for the detection of a known signal with unknown parameters corrupted by noncircular interferences

    NASA Astrophysics Data System (ADS)

    Chevalier, Pascal; Oukaci, Abdelkader; Delmas, Jean-Pierre

    2011-12-01

    The detection of a known signal with unknown parameters in the presence of noise plus interferences (called total noise) whose covariance matrix is unknown is an important problem which has received much attention these last decades for applications such as radar, satellite localization or time acquisition in radio communications. However, most of the available receivers assume a second order (SO) circular (or proper) total noise and become suboptimal in the presence of SO noncircular (or improper) interferences, potentially present in the previous applications. The scarce available receivers which take the potential SO noncircularity of the total noise into account have been developed under the restrictive condition of a known signal with known parameters or under the assumption of a random signal. For this reason, following a generalized likelihood ratio test (GLRT) approach, the purpose of this paper is to introduce and to analyze the performance of different array receivers for the detection of a known signal, with different sets of unknown parameters, corrupted by an unknown noncircular total noise. To simplify the study, we limit the analysis to rectilinear known useful signals for which the baseband signal is real, which concerns many applications.

  20. Unknown foundation determination for scour.

    DOT National Transportation Integrated Search

    2012-04-01

    Unknown foundations affect about 9,000 bridges in Texas. For bridges over rivers, this creates a problem : regarding scour decisions as the calculated scour depth cannot be compared to the foundation depth, and a : very conservative costly approach m...

  1. Prevalence of antineuronal antibodies in patients with encephalopathy of unknown etiology: Data from a nationwide registry in Korea.

    PubMed

    Byun, Jung-Ick; Lee, Soon-Tae; Jung, Keun-Hwa; Sunwoo, Jun-Sang; Moon, Jangsup; Kim, Tae-Joon; Lim, Jung-Ah; Kim, Soyun; Kim, Do-Yong; Han, Su-Hyun; Jang, Hyemin; Suh, Hong Il; Cho, A-Hyun; Kim, Dong Wook; Shin, Jung-Won; Koo, Yong Seo; Choi, Woo Chan; Lee, Woong-Woo; Choi, Nari; Kim, Seongheon; Nam, Hyunwoo; Koo, Dae Lim; Kim, Minah; Lim, Byung Chan; Chae, Jong-Hee; Kim, Ki Joong; Jeon, Daejong; Park, Kyung-Il; Jung, Ki-Young; Kim, Manho; Chu, Kon; Lee, Sang Kun

    2016-04-15

    We aimed to evaluate the prevalence of antineuronal antibodies in a nationwide cohort of patients with encephalopathy of unknown etiology. We screened 1699 patients with idiopathic encephalopathy who were referred from 70 hospitals across Korea for autoimmune synaptic and classic paraneoplastic antibodies. Those with cerebellar degeneration, sensory polyneuropathy or other paraneoplastic syndromes without encephalopathy were not included in this study. One-hundred and four patients (6.12%) had antibody-associated autoimmune encephalopathy. Autoimmune synaptic antibodies were identified in 89 patients (5.24%) and classic paraneoplastic antibodies were identified in 16 patients (0.94%). The patients with antibody-associated autoimmune encephalopathy comprised a small but significant portion of the total number of patients with encephalopathy of unknown cause. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Proposed Confidence Scale and ID Score in the Identification of Known-Unknown Compounds Using High Resolution MS Data

    NASA Astrophysics Data System (ADS)

    Rochat, Bertrand

    2017-04-01

    High-resolution (HR) MS instruments recording HR-full scan allow analysts to go further beyond pre-acquisition choices. Untargeted acquisition can reveal unexpected compounds or concentrations and can be performed for preliminary diagnosis attempt. Then, revealed compounds will have to be identified for interpretations. Whereas the need of reference standards is mandatory to confirm identification, the diverse information collected from HRMS allows identifying unknown compounds with relatively high degree of confidence without reference standards injected in the same analytical sequence. However, there is a necessity to evaluate the degree of confidence in putative identifications, possibly before further targeted analyses. This is why a confidence scale and a score in the identification of (non-peptidic) known-unknown, defined as compounds with entries in database, is proposed for (LC-) HRMS data. The scale is based on two representative documents edited by the European Commission (2007/657/EC) and the Metabolomics Standard Initiative (MSI), in an attempt to build a bridge between the communities of metabolomics and screening labs. With this confidence scale, an identification (ID) score is determined as [a number, a letter, and a number] (e.g., 2D3), from the following three criteria: I, a General Identification Category (1, confirmed, 2, putatively identified, 3, annotated compounds/classes, and 4, unknown); II, a Chromatography Class based on the relative retention time (from the narrowest tolerance, A, to no chromatographic references, D); and III, an Identification Point Level (1, very high, 2, high, and 3, normal level) based on the number of identification points collected. Three putative identification examples of known-unknown will be presented.

  3. Global identifiability of linear compartmental models--a computer algebra algorithm.

    PubMed

    Audoly, S; D'Angiò, L; Saccomani, M P; Cobelli, C

    1998-01-01

    A priori global identifiability deals with the uniqueness of the solution for the unknown parameters of a model and is, thus, a prerequisite for parameter estimation of biological dynamic models. Global identifiability is however difficult to test, since it requires solving a system of algebraic nonlinear equations which increases both in nonlinearity degree and number of terms and unknowns with increasing model order. In this paper, a computer algebra tool, GLOBI (GLOBal Identifiability) is presented, which combines the topological transfer function method with the Buchberger algorithm, to test global identifiability of linear compartmental models. GLOBI allows for the automatic testing of a priori global identifiability of general structure compartmental models from general multi input-multi output experiments. Examples of usage of GLOBI to analyze a priori global identifiability of some complex biological compartmental models are provided.

  4. Identifying DNA-binding proteins using structural motifs and the electrostatic potential

    PubMed Central

    Shanahan, Hugh P.; Garcia, Mario A.; Jones, Susan; Thornton, Janet M.

    2004-01-01

    Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA-binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix–turn-helix (HTH), helix–hairpin–helix (HhH) and helix–loop–helix (HLH). We find that the combination of these variables detect 78% of proteins with an HTH motif, which is a substantial improvement over previous work based purely on structural templates and is comparable to more complex methods of identifying DNA-binding proteins. Similar true positive fractions are achieved for the HhH and HLH motifs. We see evidence of wide evolutionary diversity for DNA-binding proteins with an HTH motif, and much smaller diversity for those with an HhH or HLH motif. PMID:15356290

  5. Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction.

    PubMed

    Tengs, Torstein; Zhang, Haibo; Holst-Jensen, Arne; Bohlin, Jon; Butenko, Melinka A; Kristoffersen, Anja Bråthen; Sorteberg, Hilde-Gunn Opsahl; Berdal, Knut G

    2009-10-08

    When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown. We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of Arabidopsis thaliana and published EST datasets from commercially relevant species (rice and papaya). We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs.

  6. Loss of function at RAE2, a previously unidentified EPFL, is required for awnlessness in cultivated Asian rice.

    PubMed

    Bessho-Uehara, Kanako; Wang, Diane R; Furuta, Tomoyuki; Minami, Anzu; Nagai, Keisuke; Gamuyao, Rico; Asano, Kenji; Angeles-Shim, Rosalyn B; Shimizu, Yoshihiro; Ayano, Madoka; Komeda, Norio; Doi, Kazuyuki; Miura, Kotaro; Toda, Yosuke; Kinoshita, Toshinori; Okuda, Satohiro; Higashiyama, Tetsuya; Nomoto, Mika; Tada, Yasuomi; Shinohara, Hidefumi; Matsubayashi, Yoshikatsu; Greenberg, Anthony; Wu, Jianzhong; Yasui, Hideshi; Yoshimura, Atsushi; Mori, Hitoshi; McCouch, Susan R; Ashikari, Motoyuki

    2016-08-09

    Domestication of crops based on artificial selection has contributed numerous beneficial traits for agriculture. Wild characteristics such as red pericarp and seed shattering were lost in both Asian (Oryza sativa) and African (Oryza glaberrima) cultivated rice species as a result of human selection on common genes. Awnedness, in contrast, is a trait that has been lost in both cultivated species due to selection on different sets of genes. In a previous report, we revealed that at least three loci regulate awn development in rice; however, the molecular mechanism underlying awnlessness remains unknown. Here we isolate and characterize a previously unidentified EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family member named REGULATOR OF AWN ELONGATION 2 (RAE2) and identify one of its requisite processing enzymes, SUBTILISIN-LIKE PROTEASE 1 (SLP1). The RAE2 precursor is specifically cleaved by SLP1 in the rice spikelet, where the mature RAE2 peptide subsequently induces awn elongation. Analysis of RAE2 sequence diversity identified a highly variable GC-rich region harboring multiple independent mutations underlying protein-length variation that disrupt the function of the RAE2 protein and condition the awnless phenotype in Asian rice. Cultivated African rice, on the other hand, retained the functional RAE2 allele despite its awnless phenotype. Our findings illuminate the molecular function of RAE2 in awn development and shed light on the independent domestication histories of Asian and African cultivated rice.

  7. Application of ion-trap mass spectrometry for identification and structural determination of an unknown impurity in simvastatin.

    PubMed

    Reddy, G V Ram; Kumar, A Praveen; Reddy, B Venkateswara; Sreeramulu, J

    2009-10-01

    Anhydro-simvastatin and simvastatin dimer are the two main impurities in the fermentation broth as well as in the final product of simvastatin, which is a hypolipidemic drug. An unknown impurity with m/z 451 for [(M + H)(+)] was detected in the analysis of final simvastatin drug sample. By using reverse phase high performance liquid chromatography (HPLC)-mass spectrometry (MS) and MS/MS spectra, the unknown impurity was detected and identified. Separation was achieved on ACE-5 C18 (150 x 4.6 mm, 3 microm column) at the flow rate of 1.2 ml min(-1) applying gradient elution of mobile phase A consisting of Milli-Q water of pH 3.0 with formic acid and B consisting of acetonitrile. MS/MS spectrum of the unknown impurity was obtained using HPLC-MS equipped with positive electrosoray ionization (ESI). The unknown impurity is named as 7-[7-(2,2-dimethyl-butyryloxy)-2,6-dimethyl-1,2,6,7,8,8a-hexahydro-naphthalen-1 -yl]-3-hydroxy-5-hydroxymethyl-heptanoic acid.

  8. Online self-test identifies women at high familial breast cancer risk in population-based breast cancer screening without inducing anxiety or distress.

    PubMed

    van Erkelens, A; Sie, A S; Manders, P; Visser, A; Duijm, L E; Mann, R M; Ten Voorde, M; Kroeze, H; Prins, J B; Hoogerbrugge, N

    2017-06-01

    Identifying high familial breast cancer (FBC) risk improves detection of yet unknown BRCA1/2-mutation carriers, for whom BC risk is both highly likely and potentially preventable. We assessed whether a new online self-test could identify women at high FBC risk in population-based BC screening without inducing anxiety or distress. After their visit for screening mammography, women were invited by email to take an online self-test for identifying highly increased FBC risk-based on Dutch guidelines. Exclusion criteria were previously diagnosed as increased FBC risk or a personal history of BC. Anxiety (State-Trait Anxiety Inventory Dutch Version), distress (Hospital Anxiety Depression Scale) and BC risk perception were assessed using questionnaires, which were completed immediately before and after taking the online self-test and 2 weeks later. Of the 562 women invited by email, 406 (72%) completed the online self-test while 304 also completed questionnaires (response rate 54%). After exclusion criteria, 287 (51%) were included for data analysis. Median age was 56 years (range 50-74). A high or moderate FBC risk was identified in 12 (4%) and three (1%) women, respectively. After completion of the online self-test, anxiety and BC risk perception were decreased while distress scores remained unchanged. Levels were below clinical relevance. Most women (85%) would recommend the self-test; few (3%) would not. The online self-test identified previously unknown women at high FBC risk (4%), who may carry a BRCA1/2-mutation, without inducing anxiety or distress. We therefore recommend offering this self-test to women who attend population-based screening mammography for the first time. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Learning from the Unknown Student

    ERIC Educational Resources Information Center

    Barlow, Angela T.; Gerstenschlager, Natasha E.; Harmon, Shannon E.

    2016-01-01

    In this article, three instructional situations demonstrate the value of using an "unknown" student's work to allow the advancement of students' mathematical thinking as well as their engagement in the mathematical practice of critiquing the reasoning of others: (1) introducing alternative solution strategies; (2) critiquing inaccuracies…

  10. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

    PubMed

    Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

    2015-09-22

    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

  11. Pregnancy of unknown location: Outcome in a tertiary care hospital.

    PubMed

    Amer, Nuzhat; Amer, Muhammad; Kolkaila, Mohamed Abdoh; Yaqoob, Shahida

    2015-10-01

    To find out the outcome of a cohort of women with pregnancy of unknown location presenting to a tertiary care hospital. The prospective study was conducted from January to December, 2011, at Early Pregnancy Assessment Unit, King Faisal Military Hospital, Khamis Mushait, Saudi Arabia. Data was collected for women with early pregnancy or with history of amenorrhoea, bleeding or pain. These women were investigated with serum beta-human chorionic gonadotrophin levels twice weekly and transvaginal ultrasonography weekly. Expectant management was done for failing pregnancy of unknown location while medical or surgical management was considered for persistent pregnancy of unknown location and ectopic pregnancy. During study period, 7215 patients were admitted, and, of them, 2212(30.6%) were patients with early pregnancy. Meeting the inclusion criteria were 183(2.53%) patients who formed the study sample. There were 131(71.6%) patients presenting with amenorrhoea, 90(49.2%) had bleeding and 93(50.8%) presented with pain. Outcome of 100(54.6%) patients was failing pregnancy of unknown location, 58(31.7%) had intrauterine pregnancy, 14(7.7%) converted to ectopic pregnancy, while 11(6%) had persistent pregnancy of unknown location. All patients with persistent pregnancy of unknown location and 5(36%) patients with ectopic pregnancy were medically treated. Five (36%) patients having ectopic pregnancy were managed surgically. Management of choice for asymptomatic patients having pregnancy of unknown location is expectant management. Most of the patients suspected to have Most of the patients with persistent pregnancy of unknown location and ectopic pregnancy can be managed medically.

  12. Drug Resistance in Newly Presenting and Previously Treated Tuberculosis Patients in Guangxi Province, People's Republic of China.

    PubMed

    Luo, Dan; Zhao, Jinming; Lin, Mei; Liu, Feiying; Huang, Shuhai; Zhang, Yingkun; Huang, Minying; Li, Juan; Zhou, Yang; Lan, Rushu; Zhao, Yanlin

    2017-05-01

    Drug-resistant Mycobacterium tuberculosis strains are a major threat to the control of tuberculosis (TB), but the prevalence of drug-resistant TB is still unknown in the southern ethnic region of China. A cluster-randomized sampling method was used to include the study population. Isolates were tested for resistance to 6 antituberculosis drugs, and genotyped to identify Beijing strains. Overall, 11.3% (139/1229) of new cases and 33.0% (126/382) of retreated cases had drug-resistant tuberculosis. Multiple previous TB treatment episodes and multiple treatment interruptions were risk factors for both drug-resistant and multidrug-resistant TB among retreated cases. A total of 53.2% of the patients were infected with a Beijing strain of M tuberculosis. Infection with a Beijing strain was significantly associated with drug resistance among new cases (odds ratio, 1.44; 95% CI, 1.01-2.07). Novel strategies to rapid diagnosis and effective treatment are urgently needed to prevent the development of drug resistance.

  13. Students' Conscious Unknowns about Artefacts and Natural Objects

    ERIC Educational Resources Information Center

    Vaz-Rebelo, Piedade; Fernandes, Paula; Morgado, Julia; Monteiro, António; Otero, José

    2016-01-01

    This study attempts to characterise what 7th- and 12th-grade students believe they do not know about artefacts and natural objects, as well as the dependence of what is unknown on a knowledge of these objects. The students were asked to make explicit through questioning what they did not know about a sample of objects. The unknowns generated were…

  14. Clinical characteristics of children with mental retardation of unknown etiology in Korea.

    PubMed Central

    Yim, S. Y.; Lee, I. Y.

    1999-01-01

    The purpose of this study was to investigate the clinical characteristics of children with mental retardation (MR) of unknown etiology for early recognition and intervention. In this study, we defined children with MR of unknown etiology as those without clear etiologies for MR despite extensive evaluation and were not associated with pathological behavioral problems such as pervasive developmental disorders and attention-deficit/hyperactivity disorder. The clinical characteristics of children with MR of unknown etiology were as follows. 1) MR of unknown etiology was 48.8% of all MR. 2) MR of unknown etiology was more common in males. 3) Delayed language development was a leading factor that made the parents of children with MR of unknown etiology seek help from physicians. However, most of the children with MR of unknown etiology showed a relatively uniform delay in several areas of development. 4) Most children with MR of unknown etiology were delayed walkers. 5) Most children with MR of unknown etiology were mild cases. PMID:10331556

  15. Prescribed performance distributed consensus control for nonlinear multi-agent systems with unknown dead-zone input

    NASA Astrophysics Data System (ADS)

    Cui, Guozeng; Xu, Shengyuan; Ma, Qian; Li, Yongmin; Zhang, Zhengqiang

    2018-05-01

    In this paper, the problem of prescribed performance distributed output consensus for higher-order non-affine nonlinear multi-agent systems with unknown dead-zone input is investigated. Fuzzy logical systems are utilised to identify the unknown nonlinearities. By introducing prescribed performance, the transient and steady performance of synchronisation errors are guaranteed. Based on Lyapunov stability theory and the dynamic surface control technique, a new distributed consensus algorithm for non-affine nonlinear multi-agent systems is proposed, which ensures cooperatively uniformly ultimately boundedness of all signals in the closed-loop systems and enables the output of each follower to synchronise with the leader within predefined bounded error. Finally, simulation examples are provided to demonstrate the effectiveness of the proposed control scheme.

  16. Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study

    PubMed Central

    Naito, Toshio; Mizooka, Masafumi; Mitsumoto, Fujiko; Kanazawa, Kenji; Torikai, Keito; Ohno, Shiro; Morita, Hiroyuki; Ukimura, Akira; Mishima, Nobuhiko; Otsuka, Fumio; Ohyama, Yoshio; Nara, Noriko; Murakami, Kazunari; Mashiba, Kouichi; Akazawa, Kenichiro; Yamamoto, Koji; Senda, Shoichi; Yamanouchi, Masashi; Tazuma, Susumu; Hayashi, Jun

    2013-01-01

    Objective Fever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO. Design A nationwide retrospective study. Setting 17 hospitals affiliated with the Japanese Society of Hospital General Medicine. Participants This study included patients ≥18 years diagnosed with ‘classical fever of unknown origin’ (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011. Results A total of 121 patients with FUO were enrolled. The median age was 59 years (range 19–94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients. Conclusions With the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO. PMID:24362014

  17. Novel genetic loci underlying human intracranial volume identified through genome-wide association.

    PubMed

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-12-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  18. Non-destructive identification of unknown minor phases in polycrystalline bulk alloys using three-dimensional X-ray diffraction

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

    Yang, Yiming, E-mail: yangyiming1988@outlook.com

    Minor phases make considerable contributions to the mechanical and physical properties of metals and alloys. Unfortunately, it is difficult to identify unknown minor phases in a bulk polycrystalline material using conventional metallographic methods. Here, a non-destructive method based on three-dimensional X-ray diffraction (3DXRD) is developed to solve this problem. Simulation results demonstrate that this method is simultaneously able to identify minor phase grains and reveal their positions, orientations and sizes within bulk alloys. According to systematic simulations, the 3DXRD method is practicable for an extensive sample set, including polycrystalline alloys with hexagonal, orthorhombic and cubic minor phases. Experiments were alsomore » conducted to confirm the simulation results. The results for a bulk sample of aluminum alloy AA6061 show that the crystal grains of an unexpected γ-Fe (austenite) phase can be identified, three-dimensionally and nondestructively. Therefore, we conclude that the 3DXRD method is a powerful tool for the identification of unknown minor phases in bulk alloys belonging to a variety of crystal systems. This method also has the potential to be used for in situ observations of the effects of minor phases on the crystallographic behaviors of alloys. - Highlights: •A method based on 3DXRD is developed for identification of unknown minor phase. •Grain position, orientation and size, is simultaneously acquired. •A systematic simulation demonstrated the applicability of the proposed method. •Experimental results on a AA6061 sample confirmed the practicability of the method.« less

  19. Global tracking for a class of uncertain nonlinear systems with unknown sign-switching control direction by output feedback

    NASA Astrophysics Data System (ADS)

    Roux Oliveira, Tiago; Jacoud Peixoto, Alessandro; Hsu, Liu

    2015-09-01

    This paper addresses the design of a sliding mode controller for a class of high-order uncertain nonlinear plants with unmatched state-dependent nonlinearities and unknown sign of the high frequency gain, i.e., the control direction is assumed unknown. Differently from most previous studies, the control direction is allowed to switch its sign. We show that it is possible to obtain global exact tracking using only output-feedback by coupling a relay periodic switching function with a norm state observer. One significant advantage of the new scheme is its robustness and improved transient response under arbitrary changes of the control direction which have been theoretically demonstrated for jump variations and successfully tested by simulations. The proposed controller is also evaluated with a DC motor control experiment.

  20. New features of the Moon revealed and identified by CLTM-s01

    NASA Astrophysics Data System (ADS)

    Huang, Qian; Ping, Jinsong; Su, Xiaoli; Shu, Rong; Tang, Geshi

    2009-12-01

    Previous analyses showed a clear asymmetry in the topography, geological material distribution, and crustal thickness between the nearside and farside of the Moon. Lunar detecting data, such as topography and gravity, have made it possible to interpret this hemisphere dichotomy. The high-resolution lunar topographic model CLTM-s01 has revealed that there still exist four unknown features, namely, quasi-impact basin Sternfeld-Lewis (20°S, 232°E), confirmed impact basin Fitzgerald-Jackson (25°N, 191°E), crater Wugang (13°N, 189°E) and volcanic deposited highland Yutu (14°N, 308°E). Furthermore, we analyzed and identified about eleven large-scale impact basins that have been proposed since 1994, and classified them according to their circular characteristics.

  1. Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

    PubMed Central

    Wang, Yimin; Du, Xiaonan; Bin, Rao; Yu, Shanshan; Xia, Zhezhi; Zheng, Guo; Zhong, Jianmin; Zhang, Yunjian; Jiang, Yong-hui; Wang, Yi

    2017-01-01

    Genetic factors play a major role in the etiology of epilepsy disorders. Recent genomics studies using next generation sequencing (NGS) technique have identified a large number of genetic variants including copy number (CNV) and single nucleotide variant (SNV) in a small set of genes from individuals with epilepsy. These discoveries have contributed significantly to evaluate the etiology of epilepsy in clinic and lay the foundation to develop molecular specific treatment. However, the molecular basis for a majority of epilepsy patients remains elusive, and furthermore, most of these studies have been conducted in Caucasian children. Here we conducted a targeted exome-sequencing of 63 trios of Chinese epilepsy families using a custom-designed NGS panel that covers 412 known and candidate genes for epilepsy. We identified pathogenic and likely pathogenic variants in 15 of 63 (23.8%) families in known epilepsy genes including SCN1A, CDKL5, STXBP1, CHD2, SCN3A, SCN9A, TSC2, MBD5, POLG and EFHC1. More importantly, we identified likely pathologic variants in several novel candidate genes such as GABRE, MYH1, and CLCN6. Our results provide the evidence supporting the application of custom-designed NGS panel in clinic and indicate a conserved genetic susceptibility for epilepsy between Chinese and Caucasian children. PMID:28074849

  2. Grouping Parturients by Parity, Previous-Cesarean, and Mode of Delivery (P-C-MoD Classification) Better Identifies Groups at Risk for Postpartum Hemorrhage.

    PubMed

    Reichman, Orna; Gal, Micahel; Sela, Hen Y; Khayyat, Izzat; Emanuel, Michael; Samueloff, Arnon

    2016-10-01

    Objective We aimed to create a clinical classification to better identify parturients at risk for postpartum hemorrhage (PPH). Method A retrospective cohort, including all women who delivered at a single tertiary care medical center, between 2006 and 2014. Parturients were grouped by parity and history of cesarean delivery (CD): primiparas, multipara, and multipara with previous CD. Each were further subgrouped by mode of delivery (spontaneous vaginal delivery [SVD], operative vaginal delivery [OVD], emergency or elective CD). In all, 12 subgroups, based on parity, previous cesarean, and mode of delivery, formed the P-C-MoD classification. PPH was defined as a decrease of ≥3 gram% hemoglobin from admission and/or transfusion of blood products. Univariate analysis followed by multivariate analysis was performed to assess risk for PPH, controlling for confounders. Results The crude rate of PPH among 126,693 parturients was 7%. The prevalence differed significantly among independent risk factors: primiparity, 14%; multiparity, 4%; OVD, 22%; and CD, 15%. The P-C-MoD classification, segregated better between parturients at risk for PPH. The prevalence of PPH was highest for primiparous undergoing OVD (27%) compared with multiparous with SVD (3%), odds ratio [OR] = 12.8 (95% confidence interval [CI],11.9-13.9). These finding were consistent in the multivariate analysis OR = 13.1 (95% CI,12.1-14.3). Conclusion Employing the P-C-MoD classification more readily identifies parturients at risk for PPH and is superior to estimations based on single risk factors. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Using Conductivity Measurements to Determine the Identities and Concentrations of Unknown Acids: An Inquiry Laboratory Experiment

    ERIC Educational Resources Information Center

    Smith, K. Christopher; Garza, Ariana

    2015-01-01

    This paper describes a student designed experiment using titrations involving conductivity measurements to identify unknown acids as being either HCl or H[subscript 2]SO[subscript 4], and to determine the concentrations of the acids, thereby improving the utility of standard acid-base titrations. Using an inquiry context, students gain experience…

  4. Central role of a bacterial two-component gene regulatory system of previously unknown function in pathogen persistence in human saliva.

    PubMed

    Shelburne, Samuel A; Sumby, Paul; Sitkiewicz, Izabela; Granville, Chanel; DeLeo, Frank R; Musser, James M

    2005-11-01

    The molecular genetic mechanisms used by bacteria to persist in humans are poorly understood. Group A Streptococcus (GAS) causes the majority of bacterial pharyngitis cases in humans and is prone to persistently inhabit the upper respiratory tract. To gain information about how GAS survives in and infects the oropharynx, we analyzed the transcriptome of a serotype M1 strain grown in saliva. The dynamic pattern of changes in transcripts of genes [spy0874/0875, herein named sptR and sptS (sptR/S), for saliva persistence] encoding a two-component gene regulatory system of unknown function suggested that SptR/S contributed to persistence of GAS in saliva. Consistent with this idea, an isogenic nonpolar mutant strain (DeltasptR) was dramatically less able to survive in saliva compared with the parental strain. Iterative expression microarray analysis of bacteria grown in saliva revealed that transcripts of several known and putative GAS virulence factor genes were decreased significantly in the DeltasptR mutant strain. Compared with the parental strain, the isogenic mutant strain also had altered transcripts of multiple genes encoding proteins involved in complex carbohydrate acquisition and utilization pathways. Western immunoblot analysis and real-time PCR analysis of GAS in throat swabs taken from humans with pharyngitis confirmed the findings. We conclude that SptR/S optimizes persistence of GAS in human saliva, apparently by strategically influencing metabolic pathways and virulence factor production. The discovery of a genetic program that significantly increased persistence of a major human pathogen in saliva enhances understanding of how bacteria survive in the host and suggests new therapeutic strategies.

  5. Teleporting an unknown quantum state with unit fidelity and unit probability via a non-maximally entangled channel and an auxiliary system

    NASA Astrophysics Data System (ADS)

    Rashvand, Taghi

    2016-11-01

    We present a new scheme for quantum teleportation that one can teleport an unknown state via a non-maximally entangled channel with certainly, using an auxiliary system. In this scheme depending on the state of the auxiliary system, one can find a class of orthogonal vectors set as a basis which by performing von Neumann measurement in each element of this class Alice can teleport an unknown state with unit fidelity and unit probability. A comparison of our scheme with some previous schemes is given and we will see that our scheme has advantages that the others do not.

  6. A novel sensitivity-based method for damage detection of structures under unknown periodic excitations

    NASA Astrophysics Data System (ADS)

    Naseralavi, S. S.; Salajegheh, E.; Fadaee, M. J.; Salajegheh, J.

    2014-06-01

    This paper presents a technique for damage detection in structures under unknown periodic excitations using the transient displacement response. The method is capable of identifying the damage parameters without finding the input excitations. We first define the concept of displacement space as a linear space in which each point represents displacements of structure under an excitation and initial condition. Roughly speaking, the method is based on the fact that structural displacements under free and forced vibrations are associated with two parallel subspaces in the displacement space. Considering this novel geometrical viewpoint, an equation called kernel parallelization equation (KPE) is derived for damage detection under unknown periodic excitations and a sensitivity-based algorithm for solving KPE is proposed accordingly. The method is evaluated via three case studies under periodic excitations, which confirm the efficiency of the proposed method.

  7. Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction

    PubMed Central

    Tengs, Torstein; Zhang, Haibo; Holst-Jensen, Arne; Bohlin, Jon; Butenko, Melinka A; Kristoffersen, Anja Bråthen; Sorteberg, Hilde-Gunn Opsahl; Berdal, Knut G

    2009-01-01

    Background When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown. Results We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of Arabidopsis thaliana and published EST datasets from commercially relevant species (rice and papaya). Conclusion We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs. PMID:19814792

  8. Deterministic Joint Assisted Cloning of Unknown Two-Qubit Entangled States

    NASA Astrophysics Data System (ADS)

    Zhan, You-Bang

    2012-06-01

    We present two schemes for perfect cloning unknown two-qubit and general two-qubit entangled states with assistance from two state preparers, respectively. In the schemes, the sender wish to teleport an unknown two-qubit (or general two-qubit) entangled state which from two state preparers to a remote receiver, and then create a perfect copy of the unknown state at her place. The schemes include two stages. The first stage of the schemes requires usual teleportation. In the second stage, to help the sender realize the quantum cloning, two state preparers perform two-qubit projective measurements on their own qubits which from the sender, then the sender can acquire a perfect copy of the unknown state. To complete the assisted cloning schemes, several novel sets of mutually orthogonal basis vectors are introduced. It is shown that, only if two state preparers collaborate with each other, and perform projective measurements under suitable measuring basis on their own qubit respectively, the sender can create a copy of the unknown state by means of some appropriate unitary operations. The advantage of the present schemes is that the total success probability for assisted cloning a perfect copy of the unknown state can reach 1.

  9. 5. Photographic copy of photograph (date unknown, original print in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photographic copy of photograph (date unknown, original print in the possession of the Wisconsin Veterans Museums). SIX COTTAGES. VIEW UNKNOWN. - Wisconsin Home for Veterans, King, Waupaca County, WI

  10. 8. Photographic copy of photograph (date unknown, original print in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Photographic copy of photograph (date unknown, original print in the possession of the Wisconsin Veterans Museums). SEVEN COTTAGES. VIEW UNKNOWN. - Wisconsin Home for Veterans, King, Waupaca County, WI

  11. Operation Sun Beam, Shot Small Boy. Project Officer's report - Project 6. 9. Correlation of present and previous electric-field measurements

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

    Reno; Fowles, H.M.

    On most previous nuclear detonations, signatures and quantitative measurements of the electric-field signals associated with the detonations was obtained at distances such that normal radiation field characteristics apply. On Small Boy, measurements were made from stations located much closer in, such as to be inside, on the boundary of and just outside the limits of the ionized sphere created by the nuclear burst. The electric-field characteristics in these regions were unknown. In the hope of providing continuity from the region of the unknown into the reasonably well-understood region of the radiation field, this project was requested to make the typicalmore » radiation-field type of measurement that had been made on previous detonations. This report covers the signature characteristics and quantitative measurements of the electric-field signal from Small Boy as seen from outside the immediate region of theoretical generating mechanism.« less

  12. Exome Sequencing Identifies Three Novel Candidate Genes Implicated in Intellectual Disability

    PubMed Central

    Azam, Maleeha; Ayub, Humaira; Vissers, Lisenka E. L. M.; Gilissen, Christian; Ali, Syeda Hafiza Benish; Riaz, Moeen; Veltman, Joris A.; Pfundt, Rolph; van Bokhoven, Hans; Qamar, Raheel

    2014-01-01

    Intellectual disability (ID) is a major health problem mostly with an unknown etiology. Recently exome sequencing of individuals with ID identified novel genes implicated in the disease. Therefore the purpose of the present study was to identify the genetic cause of ID in one syndromic and two non-syndromic Pakistani families. Whole exome of three ID probands was sequenced. Missense variations in two plausible novel genes implicated in autosomal recessive ID were identified: lysine (K)-specific methyltransferase 2B (KMT2B), zinc finger protein 589 (ZNF589), as well as hedgehog acyltransferase (HHAT) with a de novo mutation with autosomal dominant mode of inheritance. The KMT2B recessive variant is the first report of recessive Kleefstra syndrome-like phenotype. Identification of plausible causative mutations for two recessive and a dominant type of ID, in genes not previously implicated in disease, underscores the large genetic heterogeneity of ID. These results also support the viewpoint that large number of ID genes converge on limited number of common networks i.e. ZNF589 belongs to KRAB-domain zinc-finger proteins previously implicated in ID, HHAT is predicted to affect sonic hedgehog, which is involved in several disorders with ID, KMT2B associated with syndromic ID fits the epigenetic module underlying the Kleefstra syndromic spectrum. The association of these novel genes in three different Pakistani ID families highlights the importance of screening these genes in more families with similar phenotypes from different populations to confirm the involvement of these genes in pathogenesis of ID. PMID:25405613

  13. Adaptive and Innate Immune Responsiveness to Borrelia burgdorferi sensu lato in Exposed Asymptomatic Children and Children with Previous Clinical Lyme Borreliosis

    PubMed Central

    Skogman, Barbro H.; Hellberg, Sandra; Ekerfelt, Christina; Jenmalm, Maria C.; Forsberg, Pia; Ludvigsson, Johnny; Bergström, Sven; Ernerudh, Jan

    2012-01-01

    Why some individuals develop clinical manifestations in Lyme borreliosis (LB) while others remain asymptomatic is largely unknown. Therefore, we wanted to investigate adaptive and innate immune responsiveness to Borrelia burgdorferi sensu lato in exposed Borrelia-antibody-positive asymptomatic children (n = 20), children with previous clinical LB (n = 24), and controls (n = 20). Blood samples were analyzed for Borrelia-specific interferon (IFN)-γ, interleukin (IL)-4, and IL-17 secretion by ELISPOT and Borrelia-induced IL-1β, IL-6, IL-10, IL-12(p70), and tumor necrosis factor (TNF) secretion by Luminex. We found no significant differences in cytokine secretion between groups, but a tendency towards an increased spontaneous secretion of IL-6 was found among children with previous clinical LB. In conclusion, the adaptive or innate immune responsiveness to Borrelia burgdorferi sensu lato was similar in Borrelia-exposed asymptomatic children and children with previous clinical LB. Thus, the immunological mechanisms of importance for eradicating the spirochete effectively without developing clinical manifestations of LB remain unknown. PMID:22190976

  14. Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish

    PubMed Central

    Monteiro, Diana A.; Taylor, Edwin W.; Sartori, Marina R.; Cruz, André L.; Rantin, Francisco T.; Leite, Cleo A. C.

    2018-01-01

    The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems. PMID:29507882

  15. Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish.

    PubMed

    Monteiro, Diana A; Taylor, Edwin W; Sartori, Marina R; Cruz, André L; Rantin, Francisco T; Leite, Cleo A C

    2018-02-01

    The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems.

  16. A Predictive Model Has Identified Tick-Borne Encephalitis High-Risk Areas in Regions Where No Cases Were Reported Previously, Poland, 1999-2012.

    PubMed

    Stefanoff, Pawel; Rubikowska, Barbara; Bratkowski, Jakub; Ustrnul, Zbigniew; Vanwambeke, Sophie O; Rosinska, Magdalena

    2018-04-04

    During 1999–2012, 77% of the cases of tick-borne encephalitis (TBE) were recorded in two out of 16 Polish provinces. However, historical data, mostly from national serosurveys, suggest that the disease could be undetected in many areas. The aim of this study was to identify which routinely-measured meteorological, environmental, and socio-economic factors are associated to TBE human risk across Poland, with a particular focus on areas reporting few cases, but where serosurveys suggest higher incidence. We fitted a zero-inflated Poisson model using data on TBE incidence recorded in 108 NUTS-5 administrative units in high-risk areas over the period 1999–2012. Subsequently we applied the best fitting model to all Polish municipalities. Keeping the remaining variables constant, the predicted rate increased with the increase of air temperature over the previous 10–20 days, precipitation over the previous 20–30 days, in forestation, forest edge density, forest road density, and unemployment. The predicted rate decreased with increasing distance from forests. The map of predicted rates was consistent with the established risk areas. It predicted, however, high rates in provinces considered TBE-free. We recommend raising awareness among physicians working in the predicted high-risk areas and considering routine use of household animal surveys for risk mapping.

  17. Identification of unknown impurity of azelaic acid in liposomal formulation assessed by HPLC-ELSD, GC-FID, and GC-MS.

    PubMed

    Han, Stanisław; Karłowicz-Bodalska, Katarzyna; Potaczek, Piotr; Wójcik, Adam; Ozimek, Lukasz; Szura, Dorota; Musiał, Witold

    2014-02-01

    The identification of new contaminants is critical in the development of new medicinal products. Many impurities, such as pentanedioic acid, hexanedioic acid, heptanedioic acid, octanedioic acid, decanedioic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, and tetradecanedioic acid, have been identified in samples of azelaic acid. The aim of this study was to identify impurities observed during the stability tests of a new liposomal dosage form of azelaic acid that is composed of phosphatidylcholine and a mixture of ethyl alcohol and water, using high-performance liquid chromatography with evaporative light-scattering detector (HPLC-ELSD), gas chromatography-flame ionisation detection (GC-FID), and gas chromatography-mass spectrometry (GC-MS) methods. During the research and development of a new liposomal formulation of azelaic acid, we developed a method for determining the contamination of azelaic acid using HPLC-ELSD. During our analytical tests, we identified a previously unknown impurity of a liposomal preparation of azelaic acid that appeared in the liposomal formulation of azelaic acid during preliminary stability studies. The procedure led to the conclusion that the impurity was caused by the reaction of azelaic acid with one of the excipients that was applied in the product. The impurity was finally identified as an ethyl monoester of azelaic acid. The identification procedure of this compound was carried out in a series of experiments comparing the chromatograms that were obtained via the following chromatographic methods: HPLC-ELSD, GC-FID, and GC-MS. The final identification of the compound was carried out by GC with MS.

  18. "Physics is supposed to be spoken of with a bit of irony": unknown speech by L D Landau, 8 April 1960

    NASA Astrophysics Data System (ADS)

    Druzhinin, P. A.

    2018-01-01

    A previously unknown speech by Lev Landau dated 8 April 1960 has been published, as transcribed from a unique tape recording obtained from the Russian State Phonogram Archive (Moscow). This is Landau's only true public speech known to have been recorded.

  19. In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways.

    PubMed

    Heinz, Leonard P; Kopec, Wojciech; de Groot, Bert L; Fink, Rainer H A

    2018-05-02

    The ryanodine receptor 1 is a large calcium ion channel found in mammalian skeletal muscle. The ion channel gained a lot of attention recently, after multiple independent authors published near-atomic cryo electron microscopy data. Taking advantage of the unprecedented quality of structural data, we performed molecular dynamics simulations on the entire ion channel as well as on a reduced model. We calculated potentials of mean force for Ba 2+ , Ca 2+ , Mg 2+ , K + , Na + and Cl - ions using umbrella sampling to identify the key residues involved in ion permeation. We found two main binding sites for the cations, whereas the channel is strongly repulsive for chloride ions. Furthermore, the data is consistent with the model that the receptor achieves its ion selectivity by over-affinity for divalent cations in a calcium-block-like fashion. We reproduced the experimental conductance for potassium ions in permeation simulations with applied voltage. The analysis of the permeation paths shows that ions exit the pore via multiple pathways, which we suggest to be related to the experimental observation of different subconducting states.

  20. 46. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    46. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angeles, CA, Photographer, Date unknown NORTH ELEVATION - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  1. 47. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    47. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angleles, CA, Photographer, Date unknown WEST ELEVATION - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  2. 1. Historic American Buildings Survey Photographer Unknown. Furnished by Mrs ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Historic American Buildings Survey Photographer Unknown. Furnished by Mrs Mecia, Tombstone, Arizona. Date Unknown GENERAL VIEW MAIN CHURCH (SOUTHEAST ELEVATION). - San Xavier del Bac Mission, Mission Road, Tucson, Pima County, AZ

  3. A method to identify the main mode of machine tool under operating conditions

    NASA Astrophysics Data System (ADS)

    Wang, Daming; Pan, Yabing

    2017-04-01

    The identification of the modal parameters under experimental conditions is the most common procedure when solving the problem of machine tool structure vibration. However, the influence of each mode on the machine tool vibration in real working conditions remains unknown. In fact, the contributions each mode makes to the machine tool vibration during machining process are different. In this article, an active excitation modal analysis is applied to identify the modal parameters in operational condition, and the Operating Deflection Shapes (ODS) in frequencies of high level vibration that affect the quality of machining in real working conditions are obtained. Then, the ODS is decomposed by the mode shapes which are identified in operational conditions. So, the contributions each mode makes to machine tool vibration during machining process are got by decomposition coefficients. From the previous steps, we can find out the main modes which effect the machine tool more significantly in working conditions. This method was also verified to be effective by experiments.

  4. 44. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    44. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angeles, CA, Photographer, Date unknown FIRST FLOOR PLAN - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  5. 45. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angeles, CA, Photographer, Date unknown SECOND FLOOR PLAN - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  6. 51. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    51. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angeles, CA, Photographer, Date unknown EXTERIOR, ELEVATION DETAILS - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  7. 4. Photographic copy of photograph (date unknown, original print in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photographic copy of photograph (date unknown, original print in the possession of the Wisconsin Veterans Museums). COTTAGES WITH DIRT ROAD IN FOREGROUND. LOCATION UNKNOWN. - Wisconsin Home for Veterans, King, Waupaca County, WI

  8. 17. Photocopy of measured drawing (source unknown) 6 March 1945, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. Photocopy of measured drawing (source unknown) 6 March 1945, delineator unknown PROPOSED ADAPTIVE REUSE AS CLEMSON COLLEGE FACULTY CLUB, BASEMENT PLAN - Woodburn, Woodburn Road, U.S. Route 76 vicinity, Pendleton, Anderson County, SC

  9. 20. Photocopy of measured drawing (source unknown) 6 March 1945, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Photocopy of measured drawing (source unknown) 6 March 1945, delineator unknown PROPOSED ADAPTIVE REUSE AS CLEMSON COLLEGE FACULTY CLUB, ATTIC PLAN - Woodburn, Woodburn Road, U.S. Route 76 vicinity, Pendleton, Anderson County, SC

  10. 21. Photocopy of maesured drawing (source unknown) 6 March 1945, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. Photocopy of maesured drawing (source unknown) 6 March 1945, delineator unknown PROPOSED ADAPTIVE REUSE AS CLEMSON COLLEGE FACULTY CLUB, SITE PLAN - Woodburn, Woodburn Road, U.S. Route 76 vicinity, Pendleton, Anderson County, SC

  11. ON IDENTIFIABILITY OF NONLINEAR ODE MODELS AND APPLICATIONS IN VIRAL DYNAMICS

    PubMed Central

    MIAO, HONGYU; XIA, XIAOHUA; PERELSON, ALAN S.; WU, HULIN

    2011-01-01

    Ordinary differential equations (ODE) are a powerful tool for modeling dynamic processes with wide applications in a variety of scientific fields. Over the last 2 decades, ODEs have also emerged as a prevailing tool in various biomedical research fields, especially in infectious disease modeling. In practice, it is important and necessary to determine unknown parameters in ODE models based on experimental data. Identifiability analysis is the first step in determing unknown parameters in ODE models and such analysis techniques for nonlinear ODE models are still under development. In this article, we review identifiability analysis methodologies for nonlinear ODE models developed in the past one to two decades, including structural identifiability analysis, practical identifiability analysis and sensitivity-based identifiability analysis. Some advanced topics and ongoing research are also briefly reviewed. Finally, some examples from modeling viral dynamics of HIV, influenza and hepatitis viruses are given to illustrate how to apply these identifiability analysis methods in practice. PMID:21785515

  12. Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci

    PubMed Central

    Tragante, Vinicius; Barnes, Michael R.; Ganesh, Santhi K.; Lanktree, Matthew B.; Guo, Wei; Franceschini, Nora; Smith, Erin N.; Johnson, Toby; Holmes, Michael V.; Padmanabhan, Sandosh; Karczewski, Konrad J.; Almoguera, Berta; Barnard, John; Baumert, Jens; Chang, Yen-Pei Christy; Elbers, Clara C.; Farrall, Martin; Fischer, Mary E.; Gaunt, Tom R.; Gho, Johannes M.I.H.; Gieger, Christian; Goel, Anuj; Gong, Yan; Isaacs, Aaron; Kleber, Marcus E.; Leach, Irene Mateo; McDonough, Caitrin W.; Meijs, Matthijs F.L.; Melander, Olle; Nelson, Christopher P.; Nolte, Ilja M.; Pankratz, Nathan; Price, Tom S.; Shaffer, Jonathan; Shah, Sonia; Tomaszewski, Maciej; van der Most, Peter J.; Van Iperen, Erik P.A.; Vonk, Judith M.; Witkowska, Kate; Wong, Caroline O.L.; Zhang, Li; Beitelshees, Amber L.; Berenson, Gerald S.; Bhatt, Deepak L.; Brown, Morris; Burt, Amber; Cooper-DeHoff, Rhonda M.; Connell, John M.; Cruickshanks, Karen J.; Curtis, Sean P.; Davey-Smith, George; Delles, Christian; Gansevoort, Ron T.; Guo, Xiuqing; Haiqing, Shen; Hastie, Claire E.; Hofker, Marten H.; Hovingh, G. Kees; Kim, Daniel S.; Kirkland, Susan A.; Klein, Barbara E.; Klein, Ronald; Li, Yun R.; Maiwald, Steffi; Newton-Cheh, Christopher; O’Brien, Eoin T.; Onland-Moret, N. Charlotte; Palmas, Walter; Parsa, Afshin; Penninx, Brenda W.; Pettinger, Mary; Vasan, Ramachandran S.; Ranchalis, Jane E.; M Ridker, Paul; Rose, Lynda M.; Sever, Peter; Shimbo, Daichi; Steele, Laura; Stolk, Ronald P.; Thorand, Barbara; Trip, Mieke D.; van Duijn, Cornelia M.; Verschuren, W. Monique; Wijmenga, Cisca; Wyatt, Sharon; Young, J. Hunter; Zwinderman, Aeilko H.; Bezzina, Connie R.; Boerwinkle, Eric; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chasman, Daniel I.; Davidson, Karina W.; Doevendans, Pieter A.; Dominiczak, Anna F.; FitzGerald, Garret A.; Gums, John G.; Fornage, Myriam; Hakonarson, Hakon; Halder, Indrani; Hillege, Hans L.; Illig, Thomas; Jarvik, Gail P.; Johnson, Julie A.; Kastelein, John J.P.; Koenig, Wolfgang; Kumari, Meena; März, Winfried; Murray, Sarah S.; O’Connell, Jeffery R.; Oldehinkel, Albertine J.; Pankow, James S.; Rader, Daniel J.; Redline, Susan; Reilly, Muredach P.; Schadt, Eric E.; Kottke-Marchant, Kandice; Snieder, Harold; Snyder, Michael; Stanton, Alice V.; Tobin, Martin D.; Uitterlinden, André G.; van der Harst, Pim; van der Schouw, Yvonne T.; Samani, Nilesh J.; Watkins, Hugh; Johnson, Andrew D.; Reiner, Alex P.; Zhu, Xiaofeng; de Bakker, Paul I.W.; Levy, Daniel; Asselbergs, Folkert W.; Munroe, Patricia B.; Keating, Brendan J.

    2014-01-01

    Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10−7) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification. PMID:24560520

  13. 49. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    49. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angeles, CA, Photographer, Date unknown SECTION THROUGH BUILDING, LOOKING EAST - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  14. 48. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    48. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angeles, CA., Photographer, Date unknown SECTION THROUGH BUILDING, LOOKING NORTH - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  15. 19. Photocopy of measured drawing (source unknown) 6 March 1945, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Photocopy of measured drawing (source unknown) 6 March 1945, delineator unknown PROPOSED ADAPTIVE REUSE AS CLEMSON COLLEGE FACULTY CLUB, SECOND FLOOR PLAN - Woodburn, Woodburn Road, U.S. Route 76 vicinity, Pendleton, Anderson County, SC

  16. 18. Photocopy of measured drawing (source unknown) 6 March 1945, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Photocopy of measured drawing (source unknown) 6 March 1945, delineator unknown PROPOSED ADAPTIVE REUSE AS CLEMSON COLLEGE FACULTY CLUB, FIRST FLOOR PLAN - Woodburn, Woodburn Road, U.S. Route 76 vicinity, Pendleton, Anderson County, SC

  17. The Roles of Feedback and Feedforward as Humans Learn to Control Unknown Dynamic Systems.

    PubMed

    Zhang, Xingye; Wang, Shaoqian; Hoagg, Jesse B; Seigler, T Michael

    2018-02-01

    We present results from an experiment in which human subjects interact with an unknown dynamic system 40 times during a two-week period. During each interaction, subjects are asked to perform a command-following (i.e., pursuit tracking) task. Each subject's performance at that task improves from the first trial to the last trial. For each trial, we use subsystem identification to estimate each subject's feedforward (or anticipatory) control, feedback (or reactive) control, and feedback time delay. Over the 40 trials, the magnitudes of the identified feedback controllers and the identified feedback time delays do not change significantly. In contrast, the identified feedforward controllers do change significantly. By the last trial, the average identified feedforward controller approximates the inverse of the dynamic system. This observation provides evidence that a fundamental component of human learning is updating the anticipatory control until it models the inverse dynamics.

  18. General Unknown Screening by Ion Trap LC/MS/MS

    DTIC Science & Technology

    2010-04-01

    Subtitle 5 . Report Date April 2010 General Unknown Screening by Ion Trap LC/MS/MS 6 . Performing Organization Code 7. Author(s) 8... 5 Table 1: Analytical Data for Each of the...359 Compounds in the LC/MS/MS Library . . . . . . . . . . . 6 1 General Unknown ScreeninG by ion Trap lc/MS/MS INTrOduCTION The Federal Aviation

  19. Identifying micro-inversions using high-throughput sequencing reads.

    PubMed

    He, Feifei; Li, Yang; Tang, Yu-Hang; Ma, Jian; Zhu, Huaiqiu

    2016-01-11

    The identification of inversions of DNA segments shorter than read length (e.g., 100 bp), defined as micro-inversions (MIs), remains challenging for next-generation sequencing reads. It is acknowledged that MIs are important genomic variation and may play roles in causing genetic disease. However, current alignment methods are generally insensitive to detect MIs. Here we develop a novel tool, MID (Micro-Inversion Detector), to identify MIs in human genomes using next-generation sequencing reads. The algorithm of MID is designed based on a dynamic programming path-finding approach. What makes MID different from other variant detection tools is that MID can handle small MIs and multiple breakpoints within an unmapped read. Moreover, MID improves reliability in low coverage data by integrating multiple samples. Our evaluation demonstrated that MID outperforms Gustaf, which can currently detect inversions from 30 bp to 500 bp. To our knowledge, MID is the first method that can efficiently and reliably identify MIs from unmapped short next-generation sequencing reads. MID is reliable on low coverage data, which is suitable for large-scale projects such as the 1000 Genomes Project (1KGP). MID identified previously unknown MIs from the 1KGP that overlap with genes and regulatory elements in the human genome. We also identified MIs in cancer cell lines from Cancer Cell Line Encyclopedia (CCLE). Therefore our tool is expected to be useful to improve the study of MIs as a type of genetic variant in the human genome. The source code can be downloaded from: http://cqb.pku.edu.cn/ZhuLab/MID .

  20. A physarum-inspired prize-collecting steiner tree approach to identify subnetworks for drug repositioning.

    PubMed

    Sun, Yahui; Hameed, Pathima Nusrath; Verspoor, Karin; Halgamuge, Saman

    2016-12-05

    Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning. Drug Similarity Networks (DSN) are generated using the chemical, therapeutic, protein, and phenotype features of drugs. In DSNs, vertex prizes and edge costs represent the similarities and dissimilarities between drugs respectively, and terminals represent drugs in the cardiovascular class, as defined in the Anatomical Therapeutic Chemical classification system. A new Physarum-inspired Prize-Collecting Steiner Tree algorithm is proposed in this paper to identify subnetworks. We apply both the proposed algorithm and the widely-used GW algorithm to identify subnetworks in our 18 generated DSNs. In these DSNs, our proposed algorithm identifies subnetworks with an average Rand Index of 81.1%, while the GW algorithm can only identify subnetworks with an average Rand Index of 64.1%. We select 9 subnetworks with high Rand Index to find drug repositioning opportunities. 10 frequently occurring drugs in these subnetworks are identified as candidates to be repositioned for cardiovascular diseases. We find evidence to support previous discoveries that nitroglycerin, theophylline and acarbose may be able to be repositioned for cardiovascular diseases. Moreover, we identify seven previously unknown drug candidates that also may interact with the biological cardiovascular system. These discoveries show our proposed Prize-Collecting Steiner Tree approach as a promising strategy for drug repositioning.

  1. 52. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angeles, CA, Photographer, Date unknown DETAILS OF MAIN FLOOR ELEVATOR LOBBY - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  2. 53. Retail Pockets, Looking West, date unknown Historic Photograph, Photogapher ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    53. Retail Pockets, Looking West, date unknown Historic Photograph, Photogapher Unknown; Collection of William Everett, Jr. (Wilkes-Barre, PA), photocopy by Joseph E.B. Elliot - Huber Coal Breaker, 101 South Main Street, Ashley, Luzerne County, PA

  3. Altamira cave Paleolithic paintings harbor partly unknown bacterial communities.

    PubMed

    Schabereiter-Gurtner, Claudia; Saiz-Jimenez, Cesareo; Piñar, Guadalupe; Lubitz, Werner; Rölleke, Sabine

    2002-05-21

    Since it has been reported that microorganisms can affect painting pigments, Paleolithic painting microbiology deserves attention. The present study is the first report on the bacterial colonization of the valuable Paleolithic paintings in the famous Altamira cave (Spain). One sample taken from a painting area in the Polychromes Hall was analyzed culture-independently. This was the first time microbiologists were allowed to take sample material directly from Altamira paintings. Identification methods included PCR amplification of 16S rRNA genes (16S rDNA) and community fingerprinting by denaturing gradient gel electrophoresis (DGGE). The applied approach gave insight into a great bacterial taxonomic diversity, and allowed the detection of unexpected and unknown bacteria with potential effects on the conservation of the painting. Regarding the number of 29 visible DGGE bands in the community fingerprint, the numbers of analyzed clones described about 72% of the phylogenetic diversity present in the sample. Thirty-eight percent of the sequences analyzed were phylogenetically most closely related to cultivated bacteria, while the majority (62%) were most closely related to environmental 16S rDNA clones. Bacteria identified in Altamira were related with sequence similarities between 84.8 and 99.4% to members of the cosmopolitan Proteobacteria (52.3%), to members of the Acidobacterium division (23.8%), Cytophaga/Flexibacter/Bacteroides phylum (9.5%), green non-sulfur bacteria (4.8%), Planctomycetales (4.8%) and Actinobacteria (4.8%). The high number of clones most closely related to environmental 16S rDNA clones showed the broad spectrum of unknown and yet to be cultivated bacteria in Altamira cave.

  4. 50. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    50. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angleles, CA, Photographer, Date unknown ENTRANCE AND TYPICAL BAY ON FLOWER STREET - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  5. 53. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    53. Photocopy of drawing (Source unknown, 1928) Rapid Blue Print Co., Los Angeles, CA, Photographer, Date unknown DETAILS OF CORRIDORS ON SECOND - TWELFTH FLOORS - Richfield Oil Building, 555 South Flower Street, Los Angeles, Los Angeles County, CA

  6. Evaluation and management of head and neck squamous cell carcinoma of unknown primary.

    PubMed

    Martin, Jeffrey M; Galloway, Thomas J

    2015-07-01

    The diagnostic evaluation and therapeutic management of a patient with squamous cell carcinoma of an unknown primary (SCCUP) has considerably evolved over recent decades and will likely continue to change as a result of the improving ability to identify small primary tumors and better tailor the implementation of multimodality therapy. By application of the general principles of head and neck oncology, physicians and surgeons are often able to achieve satisfactory control of the disease in patients with SCCUP. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Characterization of a low-level unknown isomeric degradation product using an integrated online-offline top-down tandem mass spectrometry platform.

    PubMed

    Yu, Xiang; Warme, Christopher; Lee, Dinah; Zhang, Jing; Zhong, Wendy

    2013-10-01

    An integrated online-offline platform was developed combining automated online LC-MS fraction collection, continuous accumulation of selected ions (CASI), and offline top-down electron capture dissociation (ECD) tandem mass spectrometry experiments to identify a low-level, unknown isomeric degradant in a formulated drug product during an accelerated stability study. By identifying the diagnostic ions of the isoaspartic acid (isoAsp), the top-down ECD experiment showed that the Asp9 in exenatide was converted to isoAsp9 to form the unknown isomeric degradant. The platform described here provides an accurate, straightforward, and low limit of detection method for the analysis of Asp isomerization as well as other potential low-level degradants in therapeutic polypeptides and proteins. It is especially useful for unstable and time-sensitive degradants and impurities.

  8. Destination memory and familiarity: better memory for conversations with Elvis Presley than with unknown people.

    PubMed

    El Haj, Mohamad; Omigie, Diana; Samson, Séverine

    2015-06-01

    Familiarity is assumed to exert a beneficial effect on memory in older adults. Our paper investigated this issue specifically for destination memory, that is, memory of the destination of previously relayed information. Young and older adults were told familiar (Experiment 1) and unfamiliar (Experiment 2) proverbs associated with pictures depicting faces of celebrities (e.g., Elvis Presley) or unknown people, with a specific proverb assigned to each face. In a later recognition task, participants were presented with the previously exposed proverb-face pairs and for each pair had to decide whether they had previously relayed the given proverb to the given face. In general, destination performance was found to be higher for familiar than for unfamiliar faces. However while there was no difference between the two groups when the proverbs being relayed were unfamiliar, the advantage of face familiarity on destination memory was present only for older adults when the proverbs being relayed were familiar. Our results show that destination memory in older adults is sensitive to familiarity of both destination and output information.

  9. WORKER INHALATION DOSE COEFFICIENTS FOR RADIONUCLIDES NOT PREVIOUSLY IDENTIFIED IN ICRP PUBLICATION 68

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

    McLaughlin, David A; Schwahn, Scott O

    2011-01-01

    While inhalation dose coefficients are provided for about 800 radionuclides in International Commission on Radiological Protection (ICRP) Publication 68, many radionuclides of practical dosimetric interest for facilities such as high-energy proton accelerators are not specifically addressed, nor are organ-specific dose coefficients tabulated. The ICRP Publication 68 methodology is used, along with updated radiological decay data and metabolic data, to identify committed equivalent dose coefficients [hT(50)] and committed effective dose coefficients [e(50)] for radionuclides produced at the Oak Ridge National Laboratory s Spallation Neutron Source.

  10. Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction

    PubMed Central

    Mano, Miguel; Ippodrino, Rudy; Zentilin, Lorena; Zacchigna, Serena; Giacca, Mauro

    2015-01-01

    Viral vectors based on the adeno-associated virus (AAV) hold great promise for in vivo gene transfer; several unknowns, however, still limit the vectors’ broader and more efficient application. Here, we report the results of a high-throughput, whole-genome siRNA screening aimed at identifying cellular factors regulating AAV transduction. We identified 1,483 genes affecting vector efficiency more than 4-fold and up to 50-fold, either negatively or positively. Most of these factors have not previously been associated to AAV infection. The most effective siRNAs were independent from the virus serotype or analyzed cell type and were equally evident for single-stranded and self-complementary AAV vectors. A common characteristic of the most effective siRNAs was the induction of cellular DNA damage and activation of a cell cycle checkpoint. This information can be exploited for the development of more efficient AAV-based gene delivery procedures. Administration of the most effective siRNAs identified by the screening to the liver significantly improved in vivo AAV transduction efficiency. PMID:26305933

  11. Recovering an unknown source in a fractional diffusion problem

    NASA Astrophysics Data System (ADS)

    Rundell, William; Zhang, Zhidong

    2018-09-01

    A standard inverse problem is to determine a source which is supported in an unknown domain D from external boundary measurements. Here we consider the case of a time-independent situation where the source is equal to unity in an unknown subdomain D of a larger given domain Ω and the boundary of D has the star-like shape, i.e.

  12. A Multidisciplinary Investigation of a Polycythemia Vera Cancer Cluster of Unknown Origin

    PubMed Central

    Seaman, Vincent; Dearwent, Steve M; Gable, Debra; Lewis, Brian; Metcalf, Susan; Orloff, Ken; Tierney, Bruce; Zhu, Jane; Logue, James; Marchetto, David; Ostroff, Stephen; Hoffman, Ronald; Xu, Mingjiang; Carey, David; Erlich, Porat; Gerhard, Glenn; Roda, Paul; Iannuzzo, Joseph; Lewis, Robert; Mellow, John; Mulvihill, Linda; Myles, Zachary; Wu, Manxia; Frank, Arthur; Gross-Davis, Carol Ann; Klotz, Judith; Lynch, Adam; Weissfeld, Joel; Weinberg, Rona; Cole, Henry

    2010-01-01

    Cancer cluster investigations rarely receive significant public health resource allocations due to numerous inherent challenges and the limited success of past efforts. In 2008, a cluster of polycythemia vera, a rare blood cancer with unknown etiology, was identified in northeast Pennsylvania. A multidisciplinary group of federal and state agencies, academic institutions, and local healthcare providers subsequently developed a multifaceted research portfolio designed to better understand the cause of the cluster. This research agenda represents a unique and important opportunity to demonstrate that cancer cluster investigations can produce desirable public health and scientific outcomes when necessary resources are available. PMID:20617023

  13. Quantum jointly assisted cloning of an unknown three-dimensional equatorial state

    NASA Astrophysics Data System (ADS)

    Ma, Peng-Cheng; Chen, Gui-Bin; Li, Xiao-Wei; Zhan, You-Bang

    2018-02-01

    We present two schemes for perfectly cloning an unknown single-qutrit equatorial state with assistance from two and N state preparers, respectively. In the first scheme, the sender wishes to teleport an unknown single-qutrit equatorial state from two state preparers to a remote receiver, and then to create a perfect copy of the unknown state at her location. The scheme consists of two stages. The first stage of the scheme requires the usual teleportation. In the second stage, to help the sender realize the quantum cloning, two state preparers perform single-qutrit projective measurements on their own qutrits from the sender, then the sender can acquire a perfect copy of the unknown state. It is shown that, only if the two state preparers collaborate with each other, the sender can create a copy of the unknown state by means of some appropriate unitary operations. In the second scheme, we generalized the jointly assisted cloning in the first scheme to the case of N state prepares. In the present schemes, the total probability of success for assisted cloning of a perfect copy of the unknown state can reach 1.

  14. The known unknowns: neural representation of second-order uncertainty, and ambiguity

    PubMed Central

    Bach, Dominik R.; Hulme, Oliver; Penny, William D.; Dolan, Raymond J.

    2011-01-01

    Predictions provided by action-outcome probabilities entail a degree of (first-order) uncertainty. However, these probabilities themselves can be imprecise and embody second-order uncertainty. Tracking second-order uncertainty is important for optimal decision making and reinforcement learning. Previous functional magnetic resonance imaging investigations of second-order uncertainty in humans have drawn on an economic concept of ambiguity, where action-outcome associations in a gamble are either known (unambiguous) or completely unknown (ambiguous). Here, we relaxed the constraints associated with a purely categorical concept of ambiguity and varied the second-order uncertainty of gambles continuously, quantified as entropy over second-order probabilities. We show that second-order uncertainty influences decisions in a pessimistic way by biasing second-order probabilities, and that second-order uncertainty is negatively correlated with posterior cingulate cortex activity. The category of ambiguous (compared to non-ambiguous) gambles also biased choice in a similar direction, but was associated with distinct activation of a posterior parietal cortical area; an activation that we show reflects a different computational mechanism. Our findings indicate that behavioural and neural responses to second-order uncertainty are distinct from those associated with ambiguity and may call for a reappraisal of previous data. PMID:21451019

  15. From The Cover: Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation

    NASA Astrophysics Data System (ADS)

    Nollen, Ellen A. A.; Garcia, Susana M.; van Haaften, Gijs; Kim, Soojin; Chavez, Alejandro; Morimoto, Richard I.; Plasterk, Ronald H. A.

    2004-04-01

    Protein misfolding and the formation of aggregates are increasingly recognized components of the pathology of human genetic disease and hallmarks of many neurodegenerative disorders. As exemplified by polyglutamine diseases, the propensity for protein misfolding is associated with the length of polyglutamine expansions and age-dependent changes in protein-folding homeostasis, suggesting a critical role for a protein homeostatic buffer. To identify the complement of protein factors that protects cells against the formation of protein aggregates, we tested transgenic Caenorhabditis elegans strains expressing polyglutamine expansion yellow fluorescent protein fusion proteins at the threshold length associated with the age-dependent appearance of protein aggregation. We used genome-wide RNA interference to identify genes that, when suppressed, resulted in the premature appearance of protein aggregates. Our screen identified 186 genes corresponding to five principal classes of polyglutamine regulators: genes involved in RNA metabolism, protein synthesis, protein folding, and protein degradation; and those involved in protein trafficking. We propose that each of these classes represents a molecular machine collectively comprising the protein homeostatic buffer that responds to the expression of damaged proteins to prevent their misfolding and aggregation. protein misfolding | neurodegenerative diseases

  16. Presenilin-Based Genetic Screens in Drosophila melanogaster Identify Novel Notch Pathway Modifiers

    PubMed Central

    Mahoney, Matt B.; Parks, Annette L.; Ruddy, David A.; Tiong, Stanley Y. K.; Esengil, Hanife; Phan, Alexander C.; Philandrinos, Panos; Winter, Christopher G.; Chatterjee, Runa; Huppert, Kari; Fisher, William W.; L'Archeveque, Lynn; Mapa, Felipa A.; Woo, Wendy; Ellis, Michael C.; Curtis, Daniel

    2006-01-01

    Presenilin is the enzymatic component of γ-secretase, a multisubunit intramembrane protease that processes several transmembrane receptors, such as the amyloid precursor protein (APP). Mutations in human Presenilins lead to altered APP cleavage and early-onset Alzheimer's disease. Presenilins also play an essential role in Notch receptor cleavage and signaling. The Notch pathway is a highly conserved signaling pathway that functions during the development of multicellular organisms, including vertebrates, Drosophila, and C. elegans. Recent studies have shown that Notch signaling is sensitive to perturbations in subcellular trafficking, although the specific mechanisms are largely unknown. To identify genes that regulate Notch pathway function, we have performed two genetic screens in Drosophila for modifiers of Presenilin-dependent Notch phenotypes. We describe here the cloning and identification of 19 modifiers, including nicastrin and several genes with previously undescribed involvement in Notch biology. The predicted functions of these newly identified genes are consistent with extracellular matrix and vesicular trafficking mechanisms in Presenilin and Notch pathway regulation and suggest a novel role for γ-tubulin in the pathway. PMID:16415372

  17. Presenilin-based genetic screens in Drosophila melanogaster identify novel notch pathway modifiers.

    PubMed

    Mahoney, Matt B; Parks, Annette L; Ruddy, David A; Tiong, Stanley Y K; Esengil, Hanife; Phan, Alexander C; Philandrinos, Panos; Winter, Christopher G; Chatterjee, Runa; Huppert, Kari; Fisher, William W; L'Archeveque, Lynn; Mapa, Felipa A; Woo, Wendy; Ellis, Michael C; Curtis, Daniel

    2006-04-01

    Presenilin is the enzymatic component of gamma-secretase, a multisubunit intramembrane protease that processes several transmembrane receptors, such as the amyloid precursor protein (APP). Mutations in human Presenilins lead to altered APP cleavage and early-onset Alzheimer's disease. Presenilins also play an essential role in Notch receptor cleavage and signaling. The Notch pathway is a highly conserved signaling pathway that functions during the development of multicellular organisms, including vertebrates, Drosophila, and C. elegans. Recent studies have shown that Notch signaling is sensitive to perturbations in subcellular trafficking, although the specific mechanisms are largely unknown. To identify genes that regulate Notch pathway function, we have performed two genetic screens in Drosophila for modifiers of Presenilin-dependent Notch phenotypes. We describe here the cloning and identification of 19 modifiers, including nicastrin and several genes with previously undescribed involvement in Notch biology. The predicted functions of these newly identified genes are consistent with extracellular matrix and vesicular trafficking mechanisms in Presenilin and Notch pathway regulation and suggest a novel role for gamma-tubulin in the pathway.

  18. Bone metastases of unknown origin: epidemiology and principles of management.

    PubMed

    Piccioli, Andrea; Maccauro, Giulio; Spinelli, Maria Silvia; Biagini, Roberto; Rossi, Barbara

    2015-06-01

    Metastases are the most common malignancies involving bone; breast, prostate, lung and thyroid are the main sites of primary cancer. However, up to 30 % of patients present with bone metastases of unknown origin, where the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination, appropriate laboratory testing and modern imaging technology (CT, MRI, PET). Sometimes only extensive histopathological investigations on bone specimens from biopsy can suggest the primary malignancy. At other times, a bone lesion can have such a highly undifferentiated histological appearance that a precise pathological classification on routine hematoxylin-eosin-stained section is not possible. The authors reviewed the relevant literature in an attempt to investigate the epidemiology of the histological primaries finally identified in patients with bone metastases from occult cancer, and a strategy of management and treatment of bone metastases from occult carcinomas is suggested. Lung, liver, pancreas and gastrointestinal tract are common sites for primary occult tumors. Adenocarcinoma is the main histological type, accounting for 70 % of all cases, while undifferentiated cancer accounts for 20 %. Over the past 30 years, lung cancer is the main causative occult primary for bone metastases and has a poor prognosis with an average survival of 4-8 months. Most relevant literature focuses on the need for standardized diagnostic workup, as surgery for bone lesions should be aggressive only when they are solitary and/or the occult primaries have a good prognosis; in these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Thus, orthopedic surgery has a mainly palliative role in preventing or stabilizing pathological fractures, relieving pain and facilitating the care of the patient in an attempt

  19. Characterizing unknown systematics in large scale structure surveys

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

    Agarwal, Nishant; Ho, Shirley; Myers, Adam D.

    Photometric large scale structure (LSS) surveys probe the largest volumes in the Universe, but are inevitably limited by systematic uncertainties. Imperfect photometric calibration leads to biases in our measurements of the density fields of LSS tracers such as galaxies and quasars, and as a result in cosmological parameter estimation. Earlier studies have proposed using cross-correlations between different redshift slices or cross-correlations between different surveys to reduce the effects of such systematics. In this paper we develop a method to characterize unknown systematics. We demonstrate that while we do not have sufficient information to correct for unknown systematics in the data,more » we can obtain an estimate of their magnitude. We define a parameter to estimate contamination from unknown systematics using cross-correlations between different redshift slices and propose discarding bins in the angular power spectrum that lie outside a certain contamination tolerance level. We show that this method improves estimates of the bias using simulated data and further apply it to photometric luminous red galaxies in the Sloan Digital Sky Survey as a case study.« less

  20. Target Capturing Control for Space Robots with Unknown Mass Properties: A Self-Tuning Method Based on Gyros and Cameras.

    PubMed

    Li, Zhenyu; Wang, Bin; Liu, Hong

    2016-08-30

    Satellite capturing with free-floating space robots is still a challenging task due to the non-fixed base and unknown mass property issues. In this paper gyro and eye-in-hand camera data are adopted as an alternative choice for solving this problem. For this improved system, a new modeling approach that reduces the complexity of system control and identification is proposed. With the newly developed model, the space robot is equivalent to a ground-fixed manipulator system. Accordingly, a self-tuning control scheme is applied to handle such a control problem including unknown parameters. To determine the controller parameters, an estimator is designed based on the least-squares technique for identifying the unknown mass properties in real time. The proposed method is tested with a credible 3-dimensional ground verification experimental system, and the experimental results confirm the effectiveness of the proposed control scheme.

  1. Target Capturing Control for Space Robots with Unknown Mass Properties: A Self-Tuning Method Based on Gyros and Cameras

    PubMed Central

    Li, Zhenyu; Wang, Bin; Liu, Hong

    2016-01-01

    Satellite capturing with free-floating space robots is still a challenging task due to the non-fixed base and unknown mass property issues. In this paper gyro and eye-in-hand camera data are adopted as an alternative choice for solving this problem. For this improved system, a new modeling approach that reduces the complexity of system control and identification is proposed. With the newly developed model, the space robot is equivalent to a ground-fixed manipulator system. Accordingly, a self-tuning control scheme is applied to handle such a control problem including unknown parameters. To determine the controller parameters, an estimator is designed based on the least-squares technique for identifying the unknown mass properties in real time. The proposed method is tested with a credible 3-dimensional ground verification experimental system, and the experimental results confirm the effectiveness of the proposed control scheme. PMID:27589748

  2. Reinforcement learning for adaptive optimal control of unknown continuous-time nonlinear systems with input constraints

    NASA Astrophysics Data System (ADS)

    Yang, Xiong; Liu, Derong; Wang, Ding

    2014-03-01

    In this paper, an adaptive reinforcement learning-based solution is developed for the infinite-horizon optimal control problem of constrained-input continuous-time nonlinear systems in the presence of nonlinearities with unknown structures. Two different types of neural networks (NNs) are employed to approximate the Hamilton-Jacobi-Bellman equation. That is, an recurrent NN is constructed to identify the unknown dynamical system, and two feedforward NNs are used as the actor and the critic to approximate the optimal control and the optimal cost, respectively. Based on this framework, the action NN and the critic NN are tuned simultaneously, without the requirement for the knowledge of system drift dynamics. Moreover, by using Lyapunov's direct method, the weights of the action NN and the critic NN are guaranteed to be uniformly ultimately bounded, while keeping the closed-loop system stable. To demonstrate the effectiveness of the present approach, simulation results are illustrated.

  3. Robust Fault Detection for Switched Fuzzy Systems With Unknown Input.

    PubMed

    Han, Jian; Zhang, Huaguang; Wang, Yingchun; Sun, Xun

    2017-10-03

    This paper investigates the fault detection problem for a class of switched nonlinear systems in the T-S fuzzy framework. The unknown input is considered in the systems. A novel fault detection unknown input observer design method is proposed. Based on the proposed observer, the unknown input can be removed from the fault detection residual. The weighted H∞ performance level is considered to ensure the robustness. In addition, the weighted H₋ performance level is introduced, which can increase the sensibility of the proposed detection method. To verify the proposed scheme, a numerical simulation example and an electromechanical system simulation example are provided at the end of this paper.

  4. Switching benchmarks in cancer of unknown primary: from autopsy to microarray.

    PubMed

    Pentheroudakis, George; Golfinopoulos, Vassilios; Pavlidis, Nicholas

    2007-09-01

    Cancer of unknown primary (CUP) is associated with unknown biology and dismal prognosis. Information on the primary site of origin is scant and has never been analysed. We systematically reviewed all published evidence on the CUP primary site identified by two different approaches, either autopsy or microarray gene expression profiling. Published reports on identification of CUP primary site by autopsy or microarray-based multigene expression platforms were retrieved and analysed for year of publication, primary site, patient age, gender, histology, rate of primary identification, manifestations and metastatic deposits, microarray chip technology, training and validation sets, mathematical modelling, classification accuracy and number of classifying genes. From 1944 to 2000, a total of 884 CUP patients (66% males) underwent autopsy in 12 studies after presenting with metastatic or systemic symptoms and succumbing to their disease. A primary was identified in 644 (73%) of them, mostly in the lung (27%), pancreas (24%), hepatobiliary tree (8%), kidneys (8%), bowel, genital system and stomach, as a small focus of adenocarcinoma or poorly differentiated carcinoma. An unpredictable systemic dissemination was evident with high frequency of lung (46%), nodal (35%), bone (17%), brain (16%) and uncommon (18%) deposits. Between the 1944-1980 and the 1980-2000 series, female representation increased, 'undetermined neoplasm' diagnosis became rarer, pancreatic primaries were found less often while colonic ones were identified more frequently. Four studies using microarray technology profiled more than 500 CUP cases using classifier set of genes (ranging from 10 to 495) and reported strikingly dissimilar frequencies of assigned primary sites (lung 11.5%, pancreas 12.5%, bowel 12%, breast 15%, hepatobiliary tree 8%, kidneys 6%, genital system 9%, bladder 5%) in 75-90% of the cases. Evolution in medical imaging technology, diet and lifestyle habits probably account for changing

  5. [Determination of unknown impurities in cefotiam hexetil by HPLC-MS/MS].

    PubMed

    Tang, Qun-Xing; Liu, Ming-Dong; Yan, You-Yi; Ye, Yi; Wang, Zhi-Hui; Zhan, Lan-Fen; Liao, Lin-Chuan

    2013-05-01

    To detect unknown impurities in raw drug material of cefotiam hexetil. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed for the determination of impurities in cefotiam hexetil. Agilent SB-C18 column (150 mm x 2.1 mm i. d. , 3.5 microm particles) was used for chromatographic separations of cofotiam hexetil dissolved in deionized water, with mobile phase consisting of (A) 0.1% formic acid and (B) acetonitrile and timed gradient program T (min)/B (%): 0/3, 5/3, 15/20, 20/40, 30/60, 40/80. The flow rate was set at 0. 3 mL/min with DAD detector wavelength fixed at 254 nm. Electrospray ionization source was applied and operated in positive ion MRM mode. The source voltage was kept at 4 kV and cone voltage was 100 V with the mass range m/z 50-1000. Nitrogen was used as nebulizing gas and the nebulizer pressure was 40 psi. The drying gas temperature was 350 degrees C and the drying gas flow was 10 L/min. Results Unknown impurities of cefotiam hexetil were identified. Substance 1 was delta3-isomer of cefotiam hexetil. The structures of 3 other substances were also determined. The method is sensitive, rapid and credible for the analysis of cefotiam hexetil and its related impurities, which can be applied in quality control of cefotiam hexetil.

  6. Off-Policy Actor-Critic Structure for Optimal Control of Unknown Systems With Disturbances.

    PubMed

    Song, Ruizhuo; Lewis, Frank L; Wei, Qinglai; Zhang, Huaguang

    2016-05-01

    An optimal control method is developed for unknown continuous-time systems with unknown disturbances in this paper. The integral reinforcement learning (IRL) algorithm is presented to obtain the iterative control. Off-policy learning is used to allow the dynamics to be completely unknown. Neural networks are used to construct critic and action networks. It is shown that if there are unknown disturbances, off-policy IRL may not converge or may be biased. For reducing the influence of unknown disturbances, a disturbances compensation controller is added. It is proven that the weight errors are uniformly ultimately bounded based on Lyapunov techniques. Convergence of the Hamiltonian function is also proven. The simulation study demonstrates the effectiveness of the proposed optimal control method for unknown systems with disturbances.

  7. [Badminton--unknown sport].

    PubMed

    Zekan-Petrinović, Lidija

    2007-01-01

    For a long time, badminton was considered to be only a slow and light game for children, a game that is played outdoors and is structurally undemanding.Today, it is not an unknown and unrecognised sport, especially after it was included into the Olympics Games in 1992. Badminton is one of the oldest sports in the world. It is suitable for all ages (for children and elderly equally), women and men and even handicapped persons. Beginners can start playing badminton matches early because the basics are learned quickly. As a recreational activity, badminton is very popular in Zagreb. In the last 10 years, a number of halls specialized for badminton or offering badminton as one of available sports activities have been opened in Zagreb. At present, there are over 70 professional playgrounds for training of top contestants but also for the citizens who can play recreational badminton.

  8. Biotinylation of lysine method identifies acetylated histone H3 lysine 79 in Saccharomyces cerevisiae as a substrate for Sir2.

    PubMed

    Bheda, Poonam; Swatkoski, Stephen; Fiedler, Katherine L; Boeke, Jef D; Cotter, Robert J; Wolberger, Cynthia

    2012-04-17

    Although the biological roles of many members of the sirtuin family of lysine deacetylases have been well characterized, a broader understanding of their role in biology is limited by the challenges in identifying new substrates. We present here an in vitro method that combines biotinylation and mass spectrometry (MS) to identify substrates deacetylated by sirtuins. The method permits labeling of deacetylated residues with amine-reactive biotin on the ε-nitrogen of lysine. The biotin can be utilized to purify the substrate and identify the deacetylated lysine by MS. The biotinyl-lysine method was used to compare deacetylation of chemically acetylated histones by the yeast sirtuins, Sir2 and Hst2. Intriguingly, Sir2 preferentially deacetylates histone H3 lysine 79 as compared to Hst2. Although acetylation of K79 was not previously reported in Saccharomyces cerevisiae, we demonstrate that a minor population of this residue is indeed acetylated in vivo and show that Sir2, and not Hst2, regulates the acetylation state of H3 lysine 79. The in vitro biotinyl-lysine method combined with chemical acetylation made it possible to identify this previously unknown, low-abundance histone acetyl modification in vivo. This method has further potential to identify novel sirtuin deacetylation substrates in whole cell extracts, enabling large-scale screens for new deacetylase substrates.

  9. Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.

    PubMed

    Tragante, Vinicius; Barnes, Michael R; Ganesh, Santhi K; Lanktree, Matthew B; Guo, Wei; Franceschini, Nora; Smith, Erin N; Johnson, Toby; Holmes, Michael V; Padmanabhan, Sandosh; Karczewski, Konrad J; Almoguera, Berta; Barnard, John; Baumert, Jens; Chang, Yen-Pei Christy; Elbers, Clara C; Farrall, Martin; Fischer, Mary E; Gaunt, Tom R; Gho, Johannes M I H; Gieger, Christian; Goel, Anuj; Gong, Yan; Isaacs, Aaron; Kleber, Marcus E; Mateo Leach, Irene; McDonough, Caitrin W; Meijs, Matthijs F L; Melander, Olle; Nelson, Christopher P; Nolte, Ilja M; Pankratz, Nathan; Price, Tom S; Shaffer, Jonathan; Shah, Sonia; Tomaszewski, Maciej; van der Most, Peter J; Van Iperen, Erik P A; Vonk, Judith M; Witkowska, Kate; Wong, Caroline O L; Zhang, Li; Beitelshees, Amber L; Berenson, Gerald S; Bhatt, Deepak L; Brown, Morris; Burt, Amber; Cooper-DeHoff, Rhonda M; Connell, John M; Cruickshanks, Karen J; Curtis, Sean P; Davey-Smith, George; Delles, Christian; Gansevoort, Ron T; Guo, Xiuqing; Haiqing, Shen; Hastie, Claire E; Hofker, Marten H; Hovingh, G Kees; Kim, Daniel S; Kirkland, Susan A; Klein, Barbara E; Klein, Ronald; Li, Yun R; Maiwald, Steffi; Newton-Cheh, Christopher; O'Brien, Eoin T; Onland-Moret, N Charlotte; Palmas, Walter; Parsa, Afshin; Penninx, Brenda W; Pettinger, Mary; Vasan, Ramachandran S; Ranchalis, Jane E; M Ridker, Paul; Rose, Lynda M; Sever, Peter; Shimbo, Daichi; Steele, Laura; Stolk, Ronald P; Thorand, Barbara; Trip, Mieke D; van Duijn, Cornelia M; Verschuren, W Monique; Wijmenga, Cisca; Wyatt, Sharon; Young, J Hunter; Zwinderman, Aeilko H; Bezzina, Connie R; Boerwinkle, Eric; Casas, Juan P; Caulfield, Mark J; Chakravarti, Aravinda; Chasman, Daniel I; Davidson, Karina W; Doevendans, Pieter A; Dominiczak, Anna F; FitzGerald, Garret A; Gums, John G; Fornage, Myriam; Hakonarson, Hakon; Halder, Indrani; Hillege, Hans L; Illig, Thomas; Jarvik, Gail P; Johnson, Julie A; Kastelein, John J P; Koenig, Wolfgang; Kumari, Meena; März, Winfried; Murray, Sarah S; O'Connell, Jeffery R; Oldehinkel, Albertine J; Pankow, James S; Rader, Daniel J; Redline, Susan; Reilly, Muredach P; Schadt, Eric E; Kottke-Marchant, Kandice; Snieder, Harold; Snyder, Michael; Stanton, Alice V; Tobin, Martin D; Uitterlinden, André G; van der Harst, Pim; van der Schouw, Yvonne T; Samani, Nilesh J; Watkins, Hugh; Johnson, Andrew D; Reiner, Alex P; Zhu, Xiaofeng; de Bakker, Paul I W; Levy, Daniel; Asselbergs, Folkert W; Munroe, Patricia B; Keating, Brendan J

    2014-03-06

    Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. 39 CFR 946.4 - Disposition of property of unknown owners.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... DISPOSITION OF STOLEN MAIL MATTER AND PROPERTY ACQUIRED BY THE POSTAL INSPECTION SERVICE FOR USE AS EVIDENCE § 946.4 Disposition of property of unknown owners. (a) Where no apparent owner of property subject to... 39 Postal Service 1 2010-07-01 2010-07-01 false Disposition of property of unknown owners. 946.4...

  11. 39 CFR 946.4 - Disposition of property of unknown owners.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... DISPOSITION OF STOLEN MAIL MATTER AND PROPERTY ACQUIRED BY THE POSTAL INSPECTION SERVICE FOR USE AS EVIDENCE § 946.4 Disposition of property of unknown owners. (a) Where no apparent owner of property subject to... 39 Postal Service 1 2011-07-01 2011-07-01 false Disposition of property of unknown owners. 946.4...

  12. Bayesian source term determination with unknown covariance of measurements

    NASA Astrophysics Data System (ADS)

    Belal, Alkomiet; Tichý, Ondřej; Šmídl, Václav

    2017-04-01

    Determination of a source term of release of a hazardous material into the atmosphere is a very important task for emergency response. We are concerned with the problem of estimation of the source term in the conventional linear inverse problem, y = Mx, where the relationship between the vector of observations y is described using the source-receptor-sensitivity (SRS) matrix M and the unknown source term x. Since the system is typically ill-conditioned, the problem is recast as an optimization problem minR,B(y - Mx)TR-1(y - Mx) + xTB-1x. The first term minimizes the error of the measurements with covariance matrix R, and the second term is a regularization of the source term. There are different types of regularization arising for different choices of matrices R and B, for example, Tikhonov regularization assumes covariance matrix B as the identity matrix multiplied by scalar parameter. In this contribution, we adopt a Bayesian approach to make inference on the unknown source term x as well as unknown R and B. We assume prior on x to be a Gaussian with zero mean and unknown diagonal covariance matrix B. The covariance matrix of the likelihood R is also unknown. We consider two potential choices of the structure of the matrix R. First is the diagonal matrix and the second is a locally correlated structure using information on topology of the measuring network. Since the inference of the model is intractable, iterative variational Bayes algorithm is used for simultaneous estimation of all model parameters. The practical usefulness of our contribution is demonstrated on an application of the resulting algorithm to real data from the European Tracer Experiment (ETEX). This research is supported by EEA/Norwegian Financial Mechanism under project MSMT-28477/2014 Source-Term Determination of Radionuclide Releases by Inverse Atmospheric Dispersion Modelling (STRADI).

  13. Isolation and identification of some unknown substances in disposable nitrile-butadiene rubber gloves used for food handling.

    PubMed

    Mutsuga, M; Wakui, C; Kawamura, Y; Maitani, T

    2002-11-01

    In Japan, disposable gloves made from nitrile-butadiene rubber (NBR) are frequently used in contact with foods. In a previous paper, we investigated substances migrating from various gloves made of polyvinyl chloride, polyethylene, natural rubber and NBR. Zinc di-n-butyldithiocarbamate (ZDBC), diethyldithiocarbamate (ZDEC) used as vulcanization accelerators, di(2-ethylhexyl)phthalate (DEHP) used as a plasticizer and many unknown compounds that migrated from NBR gloves into n-heptane were detected by GC/MS. In this paper, six unknown compounds were obtained from one kind of NBR glove by n-hexane extraction and each was isolated by silica gel chromatography. From the results of NMR and mass spectral analysis of the six unknown compounds, their structures are proposed as 1,4-dione-2,5-bis(1,1-dimethylpropyl)cyclohexadiene (1), 2-(1,1-dimethylethyl)-4-(1,1,3,3-tetra methylbutyl)phenol (2), 2,6-bis(1,1-dimethylethyl)-4-(1,1,3,3-tetramethylbutyl)phenol (3), 2,4-bis(1,1,3,3-tetramethylbutyl)phenol (4), 2-(1,1-dimethylethyl)4,6-bis(1,1,3,3-tetramethylbutyl)phenol (5) and 2,4,6-tris(1,1,3,3-tetramethylbutyl)phenol (6). Compound 1 was observed in five of the seven kinds of NBR gloves, and compounds 2-4 and 6, which are not listed in Chemical Abstract (CA), were present in four kinds of gloves.

  14. New candidate loci identified by array-CGH in a cohort of 100 children presenting with syndromic obesity.

    PubMed

    Vuillaume, Marie-Laure; Naudion, Sophie; Banneau, Guillaume; Diene, Gwenaelle; Cartault, Audrey; Cailley, Dorothée; Bouron, Julie; Toutain, Jérôme; Bourrouillou, Georges; Vigouroux, Adeline; Bouneau, Laurence; Nacka, Fabienne; Kieffer, Isabelle; Arveiler, Benoit; Knoll-Gellida, Anja; Babin, Patrick J; Bieth, Eric; Jouret, Béatrice; Julia, Sophie; Sarda, Pierre; Geneviève, David; Faivre, Laurence; Lacombe, Didier; Barat, Pascal; Tauber, Maithé; Delrue, Marie-Ange; Rooryck, Caroline

    2014-08-01

    Syndromic obesity is defined by the association of obesity with one or more feature(s) including developmental delay, dysmorphic traits, and/or congenital malformations. Over 25 syndromic forms of obesity have been identified. However, most cases remain of unknown etiology. The aim of this study was to identify new candidate loci associated with syndromic obesity to find new candidate genes and to better understand molecular mechanisms involved in this pathology. We performed oligonucleotide microarray-based comparative genomic hybridization in a cohort of 100 children presenting with syndromic obesity of unknown etiology, after exhaustive clinical, biological, and molecular studies. Chromosomal copy number variations were detected in 42% of the children in our cohort, with 23% of patients with potentially pathogenic copy number variants. Our results support that chromosomal rearrangements are frequently associated with syndromic obesity with a variety of contributory genes having relevance to either obesity or developmental delay. A list of inherited or apparently de novo duplications and deletions including their enclosed genes and not previously linked to syndromic obesity was established. Proteins encoded by several of these genes are involved in lipid metabolism (ACOXL, MSMO1, MVD, and PDZK1) linked with nervous system function (BDH1 and LINGO2), neutral lipid storage (PLIN2), energy homeostasis and metabolic processes (CDH13, CNTNAP2, CPPED1, NDUFA4, PTGS2, and SOCS6). © 2014 Wiley Periodicals, Inc.

  15. Fast grasping of unknown objects using principal component analysis

    NASA Astrophysics Data System (ADS)

    Lei, Qujiang; Chen, Guangming; Wisse, Martijn

    2017-09-01

    Fast grasping of unknown objects has crucial impact on the efficiency of robot manipulation especially subjected to unfamiliar environments. In order to accelerate grasping speed of unknown objects, principal component analysis is utilized to direct the grasping process. In particular, a single-view partial point cloud is constructed and grasp candidates are allocated along the principal axis. Force balance optimization is employed to analyze possible graspable areas. The obtained graspable area with the minimal resultant force is the best zone for the final grasping execution. It is shown that an unknown object can be more quickly grasped provided that the component analysis principle axis is determined using single-view partial point cloud. To cope with the grasp uncertainty, robot motion is assisted to obtain a new viewpoint. Virtual exploration and experimental tests are carried out to verify this fast gasping algorithm. Both simulation and experimental tests demonstrated excellent performances based on the results of grasping a series of unknown objects. To minimize the grasping uncertainty, the merits of the robot hardware with two 3D cameras can be utilized to suffice the partial point cloud. As a result of utilizing the robot hardware, the grasping reliance is highly enhanced. Therefore, this research demonstrates practical significance for increasing grasping speed and thus increasing robot efficiency under unpredictable environments.

  16. Novel fluorinated surfactants tentatively identified in firefighters using liquid chromatography quadrupole time-of-flight tandem mass spectrometry and a case-control approach.

    PubMed

    Rotander, Anna; Kärrman, Anna; Toms, Leisa-Maree L; Kay, Margaret; Mueller, Jochen F; Gómez Ramos, María José

    2015-02-17

    Fluorinated surfactant-based aqueous film-forming foams (AFFFs) are made up of per- and polyfluorinated alkyl substances (PFAS) and are used to extinguish fires involving highly flammable liquids. The use of perfluorooctanesulfonic acid (PFOS) and other perfluoroalkyl acids (PFAAs) in some AFFF formulations has been linked to substantial environmental contamination. Recent studies have identified a large number of novel and infrequently reported fluorinated surfactants in different AFFF formulations. In this study, a strategy based on a case-control approach using quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) and advanced statistical methods has been used to extract and identify known and unknown PFAS in human serum associated with AFFF-exposed firefighters. Two target sulfonic acids [PFOS and perfluorohexanesulfonic acid (PFHxS)], three non-target acids [perfluoropentanesulfonic acid (PFPeS), perfluoroheptanesulfonic acid (PFHpS), and perfluorononanesulfonic acid (PFNS)], and four unknown sulfonic acids (Cl-PFOS, ketone-PFOS, ether-PFHxS, and Cl-PFHxS) were exclusively or significantly more frequently detected at higher levels in firefighters compared to controls. The application of this strategy has allowed for identification of previously unreported fluorinated chemicals in a timely and cost-efficient way.

  17. Identifying slow-moving landslides using LiDAR DEM and SAR interferometry: An Example of 2006 Meinong Earthquake

    NASA Astrophysics Data System (ADS)

    Chen, R. F.; Lin, C. W.; Hsu, Y. J.; Zhang, L.; Liang, H. Y.

    2017-12-01

    The February 6 Meinong Earthquake of 2016 (ML=6.4; at 23.85ºN, 120.81ºE), with a focal depth of 16.7 km, was triggered by an unknown blind thrust in southern Taiwan. The earthquake not only induced coseismic crustal deformation, but also triggered slow-moving landslides nearby the Longchuan active fault. In this study, high-resolution LiDAR derived DEM of 2010 is used to recognize locations of previous slow-moving landslides according to their topographic signatures, such as main escarpment, trench, double ridge, and crown cracks. Within an area of 4.5 km x 1.8 km along Longchuan fault near the ridge of Longchuan mountain, over 50 sites with landslide signatures are recognized, and three of them are over 10 ha. These earthquake-induced landslide deformations are detected from InSAR (synthetic aperture radar interferometry) images using Advanced Land Observing Satellite ALOS2/Phased-array L band and Sentinel 1 C-band SAR (PALSAR) data taken before and after the earthquake; some significant landslide deformation are even overlapped with areas where previous slow moving landslides were identified on the LiDAR DEM. Additionally, field investigation right after the earthquake in the study area also support that these previously identified landslides reactivated in the earthquake. Although these landslides do not cause serious damage due to their minor displacement in the Meinong Earthquake, the study results prove that LiDAR DEM is a powerful tool to identify and continuously monitor slow-motion landslides for preventing catastrophic failures that may be caused by hazardous earthquake or heavy rainfall.

  18. Online adaptive optimal control for continuous-time nonlinear systems with completely unknown dynamics

    NASA Astrophysics Data System (ADS)

    Lv, Yongfeng; Na, Jing; Yang, Qinmin; Wu, Xing; Guo, Yu

    2016-01-01

    An online adaptive optimal control is proposed for continuous-time nonlinear systems with completely unknown dynamics, which is achieved by developing a novel identifier-critic-based approximate dynamic programming algorithm with a dual neural network (NN) approximation structure. First, an adaptive NN identifier is designed to obviate the requirement of complete knowledge of system dynamics, and a critic NN is employed to approximate the optimal value function. Then, the optimal control law is computed based on the information from the identifier NN and the critic NN, so that the actor NN is not needed. In particular, a novel adaptive law design method with the parameter estimation error is proposed to online update the weights of both identifier NN and critic NN simultaneously, which converge to small neighbourhoods around their ideal values. The closed-loop system stability and the convergence to small vicinity around the optimal solution are all proved by means of the Lyapunov theory. The proposed adaptation algorithm is also improved to achieve finite-time convergence of the NN weights. Finally, simulation results are provided to exemplify the efficacy of the proposed methods.

  19. Adaptive exponential synchronization of complex-valued Cohen-Grossberg neural networks with known and unknown parameters.

    PubMed

    Hu, Jin; Zeng, Chunna

    2017-02-01

    The complex-valued Cohen-Grossberg neural network is a special kind of complex-valued neural network. In this paper, the synchronization problem of a class of complex-valued Cohen-Grossberg neural networks with known and unknown parameters is investigated. By using Lyapunov functionals and the adaptive control method based on parameter identification, some adaptive feedback schemes are proposed to achieve synchronization exponentially between the drive and response systems. The results obtained in this paper have extended and improved some previous works on adaptive synchronization of Cohen-Grossberg neural networks. Finally, two numerical examples are given to demonstrate the effectiveness of the theoretical results. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. A Predictive Model Has Identified Tick-Borne Encephalitis High-Risk Areas in Regions Where No Cases Were Reported Previously, Poland, 1999–2012

    PubMed Central

    Rubikowska, Barbara; Bratkowski, Jakub; Ustrnul, Zbigniew; Vanwambeke, Sophie O.

    2018-01-01

    During 1999–2012, 77% of the cases of tick-borne encephalitis (TBE) were recorded in two out of 16 Polish provinces. However, historical data, mostly from national serosurveys, suggest that the disease could be undetected in many areas. The aim of this study was to identify which routinely-measured meteorological, environmental, and socio-economic factors are associated to TBE human risk across Poland, with a particular focus on areas reporting few cases, but where serosurveys suggest higher incidence. We fitted a zero-inflated Poisson model using data on TBE incidence recorded in 108 NUTS-5 administrative units in high-risk areas over the period 1999–2012. Subsequently we applied the best fitting model to all Polish municipalities. Keeping the remaining variables constant, the predicted rate increased with the increase of air temperature over the previous 10–20 days, precipitation over the previous 20–30 days, in forestation, forest edge density, forest road density, and unemployment. The predicted rate decreased with increasing distance from forests. The map of predicted rates was consistent with the established risk areas. It predicted, however, high rates in provinces considered TBE-free. We recommend raising awareness among physicians working in the predicted high-risk areas and considering routine use of household animal surveys for risk mapping. PMID:29617333

  1. Integron-Associated DfrB4, a Previously Uncharacterized Member of the Trimethoprim-Resistant Dihydrofolate Reductase B Family, Is a Clinically Identified Emergent Source of Antibiotic Resistance.

    PubMed

    Toulouse, Jacynthe L; Edens, Thaddeus J; Alejaldre, Lorea; Manges, Amee R; Pelletier, Joelle N

    2017-05-01

    Whole-genome sequencing of trimethoprim-resistant Escherichia coli clinical isolates identified a member of the trimethoprim-resistant type II dihydrofolate reductase gene family ( dfrB ). The dfrB4 gene was located within a class I integron flanked by multiple resistance genes. This arrangement was previously reported in a 130.6-kb multiresistance plasmid. The DfrB4 protein conferred a >2,000-fold increased trimethoprim resistance on overexpression in E. coli Our results are consistent with the finding that dfrB4 contributes to clinical trimethoprim resistance. Copyright © 2017 American Society for Microbiology.

  2. A label-free optical biosensor for serotyping "unknown" influenza viruses

    NASA Astrophysics Data System (ADS)

    Zhang, Hanyuan; Henry Dunand, Carole; Wilson, Patrick; Miller, Benjamin L.

    2016-05-01

    The ability to accurately classify influenza viruses is critical to understanding patterns of infection, vaccine efficacy, and to the process of developing new vaccines. Unfortunately, this task is hampered both by the virus' ability to undergo antigenic drift and shift (rendering it a "previously unknown" strain), and by technological limitations. In an effort to overcome these challenges, we have developed a label-free human monoclonal antibody array for flu serology, using a pattern recognition approach to assign virus serotype. The array is built on the Arrayed Imaging Reflectometry (AIR) platform. AIR relies on the creation of a near-perfect antireflective condition on the surface of a silicon chip. When this antireflective condition is perturbed because of binding to an antibody spot (or other immobilized probe molecule), binding may be sensitively and quantitatively detected as an increase in reflected light. We describe fabrication and characterization of the array, and preliminary testing with isolated influenza hemagglutinin. We anticipate that this approach may be extended to other viruses by expansion of the array.

  3. Adaptive Neural Output Feedback Control for Nonstrict-Feedback Stochastic Nonlinear Systems With Unknown Backlash-Like Hysteresis and Unknown Control Directions.

    PubMed

    Yu, Zhaoxu; Li, Shugang; Yu, Zhaosheng; Li, Fangfei

    2018-04-01

    This paper investigates the problem of output feedback adaptive stabilization for a class of nonstrict-feedback stochastic nonlinear systems with both unknown backlashlike hysteresis and unknown control directions. A new linear state transformation is applied to the original system, and then, control design for the new system becomes feasible. By combining the neural network's (NN's) parameterization, variable separation technique, and Nussbaum gain function method, an input-driven observer-based adaptive NN control scheme, which involves only one parameter to be updated, is developed for such systems. All closed-loop signals are bounded in probability and the error signals remain semiglobally bounded in the fourth moment (or mean square). Finally, the effectiveness and the applicability of the proposed control design are verified by two simulation examples.

  4. No novel, high penetrant gene might remain to be found in Japanese patients with unknown MODY.

    PubMed

    Horikawa, Yukio; Hosomichi, Kazuyoshi; Enya, Mayumi; Ishiura, Hiroyuki; Suzuki, Yutaka; Tsuji, Shoji; Sugano, Sumio; Inoue, Ituro; Takeda, Jun

    2018-07-01

    MODY 5 and 6 have been shown to be low-penetrant MODYs. As the genetic background of unknown MODY is assumed to be similar, a new analytical strategy is applied here to elucidate genetic predispositions to unknown MODY. We examined to find whether there are major MODY gene loci remaining to be identified using SNP linkage analysis in Japanese. Whole-exome sequencing was performed with seven families with typical MODY. Candidates for novel MODY genes were examined combined with in silico network analysis. Some peaks were found only in either parametric or non-parametric analysis; however, none of these peaks showed a LOD score greater than 3.7, which is approved to be the significance threshold of evidence for linkage. Exome sequencing revealed that three mutated genes were common among 3 families and 42 mutated genes were common in two families. Only one of these genes, MYO5A, having rare amino acid mutations p.R849Q and p.V1601G, was involved in the biological network of known MODY genes through the intermediary of the INS. Although only one promising candidate gene, MYO5A, was identified, no novel, high penetrant MODY genes might remain to be found in Japanese MODY.

  5. Adaptive optimal control of unknown constrained-input systems using policy iteration and neural networks.

    PubMed

    Modares, Hamidreza; Lewis, Frank L; Naghibi-Sistani, Mohammad-Bagher

    2013-10-01

    This paper presents an online policy iteration (PI) algorithm to learn the continuous-time optimal control solution for unknown constrained-input systems. The proposed PI algorithm is implemented on an actor-critic structure where two neural networks (NNs) are tuned online and simultaneously to generate the optimal bounded control policy. The requirement of complete knowledge of the system dynamics is obviated by employing a novel NN identifier in conjunction with the actor and critic NNs. It is shown how the identifier weights estimation error affects the convergence of the critic NN. A novel learning rule is developed to guarantee that the identifier weights converge to small neighborhoods of their ideal values exponentially fast. To provide an easy-to-check persistence of excitation condition, the experience replay technique is used. That is, recorded past experiences are used simultaneously with current data for the adaptation of the identifier weights. Stability of the whole system consisting of the actor, critic, system state, and system identifier is guaranteed while all three networks undergo adaptation. Convergence to a near-optimal control law is also shown. The effectiveness of the proposed method is illustrated with a simulation example.

  6. Elements of person knowledge: Episodic recollection helps us to identify people but not to recognize their faces.

    PubMed

    MacKenzie, Graham; Donaldson, David I

    2016-12-01

    Faces automatically draw attention, allowing rapid assessments of personality and likely behaviour. How we respond to people is, however, highly dependent on whether we know who they are. According to face processing models person knowledge comes from an extended neural system that includes structures linked to episodic memory. Here we use scalp recorded brain signals to demonstrate the specific role of episodic memory processes during face processing. In two experiments we recorded Event-Related Potentials (ERPs) while participants made identify, familiar or unknown responses to famous faces. ERPs revealed neural signals previously associated with episodic recollection for identify but not familiar faces. These findings provide novel evidence suggesting that recollection is central to face processing, providing one source of person knowledge that can be used to moderate the initial impressions gleaned from the core neural system that supports face recognition. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  7. A note on the blind deconvolution of multiple sparse signals from unknown subspaces

    NASA Astrophysics Data System (ADS)

    Cosse, Augustin

    2017-08-01

    construction of the certificate. Recovery is certified with high probablility on the choice of the supports and distribution of the signs of each input xn on the support. The paper follows the line of previous work by Wang et al. 20163 where the authors guarantee recovery for subgaussian × Bernoulli inputs satisfying 𝔼xn|k| ∈ [1/10, 1] as soon as N ≳ L. Examples of applications include seismic imaging with unknown source or marine seismic data deghosting, magnetic resonance autocalibration or multiple channel estimation in communication. Numerical experiments are provided along with a discussion on the sample complexity tightness.

  8. 8. VIEW SHOWING THE DEMOSSING OF GRAND CANAL LOCATION UNKNOWN. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. VIEW SHOWING THE DEMOSSING OF GRAND CANAL LOCATION UNKNOWN. AT TEAM OF HORSES ON OPPOSITE BANKS OF THE CANAL DRAG A CHAIN BETWEEN THEM ALONG THE BOTTOM OF THE CANAL, WHICH PULLS THE MOSS AND WEEDS LOOSE. THE PLANS THEN FLOAT DOWN THE CANAL AND ARE CAUGHT IN A SCREEN AND REMOVED. Photographer unknown, 1923 - Grand Canal, North side of Salt River, Tempe, Maricopa County, AZ

  9. 37 CFR 260.7 - Unknown copyright owners.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Unknown copyright owners. 260.7 Section 260.7 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT ARBITRATION ROYALTY PANEL RULES AND PROCEDURES RATES AND TERMS FOR PREEXISTING SUBSCRIPTION SERVICES' DIGITAL...

  10. 37 CFR 260.7 - Unknown copyright owners.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Unknown copyright owners. 260.7 Section 260.7 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT ARBITRATION ROYALTY PANEL RULES AND PROCEDURES RATES AND TERMS FOR PREEXISTING SUBSCRIPTION SERVICES' DIGITAL...

  11. 37 CFR 260.7 - Unknown copyright owners.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Unknown copyright owners. 260.7 Section 260.7 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT ARBITRATION ROYALTY PANEL RULES AND PROCEDURES RATES AND TERMS FOR PREEXISTING SUBSCRIPTION SERVICES' DIGITAL...

  12. 37 CFR 382.7 - Unknown copyright owners.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....7 Section 382.7 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS RATES AND TERMS FOR STATUTORY LICENSES RATES AND TERMS FOR DIGITAL TRANSMISSIONS OF SOUND RECORDINGS AND... SATELLITE DIGITAL AUDIO RADIO SERVICES Preexisting Subscription Services § 382.7 Unknown copyright owners...

  13. 37 CFR 260.7 - Unknown copyright owners.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Unknown copyright owners. 260.7 Section 260.7 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT ARBITRATION ROYALTY PANEL RULES AND PROCEDURES RATES AND TERMS FOR PREEXISTING SUBSCRIPTION SERVICES' DIGITAL...

  14. 37 CFR 382.7 - Unknown copyright owners.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....7 Section 382.7 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS RATES AND TERMS FOR STATUTORY LICENSES RATES AND TERMS FOR DIGITAL TRANSMISSIONS OF SOUND RECORDINGS AND... SATELLITE DIGITAL AUDIO RADIO SERVICES Preexisting Subscription Services § 382.7 Unknown copyright owners...

  15. 37 CFR 382.7 - Unknown copyright owners.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....7 Section 382.7 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS RATES AND TERMS FOR STATUTORY LICENSES RATES AND TERMS FOR DIGITAL TRANSMISSIONS OF SOUND RECORDINGS AND... SATELLITE DIGITAL AUDIO RADIO SERVICES Preexisting Subscription Services § 382.7 Unknown copyright owners...

  16. Acute confusional state of unknown cause in the elderly: a study with continuous EEG monitoring.

    PubMed

    Naeije, Gilles; Gaspard, Nicolas; Depondt, Chantal; Pepersack, Thierry; Legros, Benjamin

    2012-03-01

    Acute confusional state (ACS) is a frequent cause of emergency consultation in the elderly. Many causes of ACS are also risk factors for seizures. Both non-convulsive seizures and status epilepticus can cause acute confusion. The yield of routine EEG may not be optimal in case of prolonged post-ictal confusion. We thus, sought to evaluate the yield of CEEG in identifying seizures in elderly patients with ACS of unknown origin. We reviewed our CEEG database for patients over 75 years with ACS and collected EEG, CEEG and clinical information. Thirty-one percent (15/48) of the CEEG performed in elderly patients were done for ACS. Routine EEG did not reveal any epileptic anomalies in 7/15 patients. Among those, CEEG identified interictal epileptiform discharges (IED) in 2 and NCSE in 1. In 8/15 patients, routine EEG revealed epileptiform abnormalities: 3 with IED (including 1 with periodic lateralized discharges), 3 with non-convulsive seizures (NCSz) and 2 with non-convulsive status epilepticus (NCSE). Among patients with only IED, CEEG revealed NCSz in 1 and NCSE in 2. This retrospective study suggests that NCSz and NCSE may account for more cases of ACS than what was previously thought. A single negative routine EEG does not exclude this diagnosis. Continuous EEG (CEEG) monitoring is more revealing than routine EEG for the detection of NCSE and NCSz in confused elderly. The presence of IED in the first routine EEG strongly suggests concomitant NCSz or NCSE. Prospective studies are required to further determine the role of CEEG monitoring in the assessment of ACS in the elderly and to establish the incidence of NCSz and NCSE in this setting. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism

    PubMed Central

    Sapkota, Yadav; Steinthorsdottir, Valgerdur; Morris, Andrew P.; Fassbender, Amelie; Rahmioglu, Nilufer; De Vivo, Immaculata; Buring, Julie E.; Zhang, Futao; Edwards, Todd L.; Jones, Sarah; O, Dorien; Peterse, Daniëlle; Rexrode, Kathryn M.; Ridker, Paul M.; Schork, Andrew J.; MacGregor, Stuart; Martin, Nicholas G.; Becker, Christian M.; Adachi, Sosuke; Yoshihara, Kosuke; Enomoto, Takayuki; Takahashi, Atsushi; Kamatani, Yoichiro; Matsuda, Koichi; Kubo, Michiaki; Thorleifsson, Gudmar; Geirsson, Reynir T.; Thorsteinsdottir, Unnur; Wallace, Leanne M.; Werge, Thomas M.; Thompson, Wesley K.; Yang, Jian; Velez Edwards, Digna R.; Nyegaard, Mette; Low, Siew-Kee; Zondervan, Krina T.; Missmer, Stacey A.; D'Hooghe, Thomas; Montgomery, Grant W.; Chasman, Daniel I.; Stefansson, Kari; Tung, Joyce Y.; Nyholt, Dale R.

    2017-01-01

    Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P<5 × 10−8), implicating genes involved in sex steroid hormone pathways (FN1, CCDC170, ESR1, SYNE1 and FSHB). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts. PMID:28537267

  18. Decentralised output feedback control of Markovian jump interconnected systems with unknown interconnections

    NASA Astrophysics Data System (ADS)

    Li, Li-Wei; Yang, Guang-Hong

    2017-07-01

    The problem of decentralised output feedback control is addressed for Markovian jump interconnected systems with unknown interconnections and general transition rates (TRs) allowed to be unknown or known with uncertainties. A class of decentralised dynamic output feedback controllers are constructed, and a cyclic-small-gain condition is exploited to dispose the unknown interconnections so that the resultant closed-loop system is stochastically stable and satisfies an H∞ performance. With slack matrices to cope with the nonlinearities incurred by unknown and uncertain TRs in control synthesis, a novel controller design condition is developed in linear matrix inequality formalism. Compared with the existing works, the proposed approach leads to less conservatism. Finally, two examples are used to illustrate the effectiveness of the new results.

  19. Identifying OH Imposters in the ALFALFA Neutral Hydrogen Survey

    NASA Astrophysics Data System (ADS)

    Suess, Katherine A.; Darling, Jeremy; Haynes, Martha P.; Giovanelli, Riccardo

    2016-06-01

    OH megamasers (OHMs) are rare, luminous molecular masers that are typically observed in (ultra) luminous infrared galaxies and serve as markers of major galaxy mergers. In blind emission line surveys such as the Arecibo Legacy Fast Arecibo L-Band Feed Array (ALFALFA) survey for neutral hydrogen (H I), OHMs at z ˜ 0.2 can mimic z ˜ 0.05 H I lines. We present the results of optical spectroscopy of ambiguous H I detections in the ALFALFA 40 per cent data release detected by the Wide Field Infrared Survey Explorer (WISE) but with uncertain optical counterparts. The optical redshifts, obtained from observations at the Apache Point Observatory, revealed five new OHMs and identified 129 H I optical counterparts. 60 candidates remain ambiguous. The new OHMs are the first detected in a blind spectral line survey. The number of OHMs in ALFALFA is consistent with predictions from the OH luminosity function. Additionally, the mid-infrared magnitudes and colours of the OHM host galaxies found in a blind survey do not seem to differ from those found in previous targeted surveys. This validates the methods used in previous IR-selected OHM surveys and indicates there is no previously unknown OHM-producing population at z ˜ 0.2. We also provide a method for future surveys to separate OH megamasers from 99 per cent of H I line emitters without optical spectroscopy by using WISE infrared colours and magnitudes. Since the fraction of OHMs found in flux-limited H I surveys is expected to increase with the survey's redshift, this selection method can be applied to future flux-limited high-redshift hydrogen surveys.

  20. Bio-media Citizenship and Chronic Kidney Disease of Unknown Etiology in Sri Lanka.

    PubMed

    de Silva, M W Amarasiri

    2018-04-01

    In this article, I examine the crucial role of the biomedical industry, epidemiological and biomedical research, and the media in forming attitudes to and the understanding of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka. Local conceptions of CKDu have been shaped by the circulation in the media of epidemiological research findings pertaining to the disease, biomedical interventions in the management of the disease in hospitals and clinics, community programs involving mass blood surveys and the testing of well water, and local food and health education programs carried out through village health committees. This process of circulation I identify as bio-media citizenship.

  1. [Standard of care of carcinomas on cancer of unknown primary site in 2016].

    PubMed

    Benderra, Marc-Antoine; Ilié, Marius; Hofman, Paul; Massard, Christophe

    2016-01-01

    Patients with Cancer of unknown primary (cup) represent 2-10%, and have disseminated cancers for which we cannot find the primary site despite the clinical, pathological and radiological exams at our disposal. Diagnosis is based on a thorough clinical and histopathologic examination as well as new imaging techniques. Several clinicopathologic entities requiring specific treatment can be identified. Genome sequencing and liquid biopsy (circulating tumor cells and tumor free DNA) could allow further advances in the diagnosis. Therapeutically, in addition to surgery, radiotherapy and chemotherapy, precision medicine provides new therapeutic approaches. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  2. Discovery of a meta-stable Al-Sm phase with unknown stoichiometry using a genetic algorithm

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

    Zhang, Feng; McBrearty, Ian; Ott, R. T.

    Unknown crystalline phases observed during the devitrification process of glassy metal alloys significantly limit our ability to understand and control phase selection in these systems driven far from equilibrium. Here, we report a new meta-stable Al 5Sm phase identified by simultaneously searching Al-rich compositions of the Al–Sm system, using an efficient genetic algorithm. The excellent match between calculated and experimental X-ray diffraction patterns confirms that this new phase appeared in the crystallization of melt-spun Al 90Sm 10 alloys.

  3. Towards high-speed autonomous navigation of unknown environments

    NASA Astrophysics Data System (ADS)

    Richter, Charles; Roy, Nicholas

    2015-05-01

    In this paper, we summarize recent research enabling high-speed navigation in unknown environments for dynamic robots that perceive the world through onboard sensors. Many existing solutions to this problem guarantee safety by making the conservative assumption that any unknown portion of the map may contain an obstacle, and therefore constrain planned motions to lie entirely within known free space. In this work, we observe that safety constraints may significantly limit performance and that faster navigation is possible if the planner reasons about collision with unobserved obstacles probabilistically. Our overall approach is to use machine learning to approximate the expected costs of collision using the current state of the map and the planned trajectory. Our contribution is to demonstrate fast but safe planning using a learned function to predict future collision probabilities.

  4. Discovery of a meta-stable Al–Sm phase with unknown stoichiometry using a genetic algorithm

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

    Zhang, Feng; McBrearty, Ian; Ott, R T

    Unknown crystalline phases observed during the devitrification process of glassy metal alloys significantly limit our ability to understand and control phase selection in these systems driven far from equilibrium. Here, we report a new meta-stable Al5Sm phase identified by simultaneously searching Al-rich compositions of the Al-Sm system, using an efficient genetic algorithm. The excellent match between calculated and experimental X-ray diffraction patterns confirms that this new phase appeared in the crystallization of melt-spun Al90Sm10 alloys. Published by Elsevier Ltd. on behalf of Acta Materialia Inc.

  5. The Information Available to a Moving Observer on Shape with Unknown, Isotropic BRDFs.

    PubMed

    Chandraker, Manmohan

    2016-07-01

    Psychophysical studies show motion cues inform about shape even with unknown reflectance. Recent works in computer vision have considered shape recovery for an object of unknown BRDF using light source or object motions. This paper proposes a theory that addresses the remaining problem of determining shape from the (small or differential) motion of the camera, for unknown isotropic BRDFs. Our theory derives a differential stereo relation that relates camera motion to surface depth, which generalizes traditional Lambertian assumptions. Under orthographic projection, we show differential stereo may not determine shape for general BRDFs, but suffices to yield an invariant for several restricted (still unknown) BRDFs exhibited by common materials. For the perspective case, we show that differential stereo yields the surface depth for unknown isotropic BRDF and unknown directional lighting, while additional constraints are obtained with restrictions on the BRDF or lighting. The limits imposed by our theory are intrinsic to the shape recovery problem and independent of choice of reconstruction method. We also illustrate trends shared by theories on shape from differential motion of light source, object or camera, to relate the hardness of surface reconstruction to the complexity of imaging setup.

  6. Rendezvous with connectivity preservation for multi-robot systems with an unknown leader

    NASA Astrophysics Data System (ADS)

    Dong, Yi

    2018-02-01

    This paper studies the leader-following rendezvous problem with connectivity preservation for multi-agent systems composed of uncertain multi-robot systems subject to external disturbances and an unknown leader, both of which are generated by a so-called exosystem with parametric uncertainty. By combining internal model design, potential function technique and adaptive control, two distributed control strategies are proposed to maintain the connectivity of the communication network, to achieve the asymptotic tracking of all the followers to the output of the unknown leader system, as well as to reject unknown external disturbances. It is also worth to mention that the uncertain parameters in the multi-robot systems and exosystem are further allowed to belong to unknown and unbounded sets when applying the second fully distributed control law containing a dynamic gain inspired by high-gain adaptive control or self-tuning regulator.

  7. Lupus erythematosus cells in bone marrow: the only clue to a previously unsuspected diagnosis of systemic lupus erythematosus.

    PubMed

    Pujani, Mukta; Kushwaha, Shivani; Sethi, Neha; Beniwal, Anu; Shukla, Shailaja

    2013-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease characterized by the development of antinuclear antibodies. Nowadays considered outdated, lupus erythematosus (LE) cell preparation served as a screening test for SLE for decades. However, the importance of discovering LE cells on routine cytology cannot be overemphasized. We report the case of a 30-year-old female in whom bone marrow aspiration (BMA) was performed during an investigative workup for pyrexia of unknown origin. The observation of LE cells in direct bone marrow smears (without the use of an anticoagulant) raised the suspicion of SLE, which was later confirmed by antinuclear antibody testing. In the present case, LE cells were observed on BMA performed for the investigation of fever of unknown origin. The unexpected observation of LE cells in BMA smears emphasizes the fact that good morphological observation of marrow aspirates can provide crucial clues to a previously unsuspected diagnosis.

  8. Method for genetic identification of unknown organisms

    DOEpatents

    Colston, Jr., Billy W.; Fitch, Joseph P.; Hindson, Benjamin J.; Carter, Chance J.; Beer, Neil Reginald

    2016-08-23

    A method of rapid, genome and proteome based identification of unknown pathogenic or non-pathogenic organisms in a complex sample. The entire sample is analyzed by creating millions of emulsion encapsulated microdroplets, each containing a single pathogenic or non-pathogenic organism sized particle and appropriate reagents for amplification. Following amplification, the amplified product is analyzed.

  9. Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis.

    PubMed

    Chandriani, Sanjay; Skewes-Cox, Peter; Zhong, Weidong; Ganem, Donald E; Divers, Thomas J; Van Blaricum, Anita J; Tennant, Bud C; Kistler, Amy L

    2013-04-09

    Theiler's disease is an acute hepatitis in horses that is associated with the administration of equine blood products; its etiologic agent has remained unknown for nearly a century. Here, we used massively parallel sequencing to explore samples from a recent Theiler's disease outbreak. Metatranscriptomic analysis of the short sequence reads identified a 10.5-kb sequence from a previously undescribed virus of the Flaviviridae family, which we designate "Theiler's disease-associated virus" (TDAV). Phylogenetic analysis clusters TDAV with GB viruses of the recently proposed Pegivirus genus, although it shares only 35.3% amino acid identity with its closest relative, GB virus D. An epidemiological survey of additional horses from three separate locations supports an association between TDAV infection and acute serum hepatitis. Experimental inoculation of horses with TDAV-positive plasma provides evidence that several weeks of viremia preceded liver injury and that liver disease may not be directly related to the level of viremia. Like hepatitis C virus, the best characterized Flaviviridae species known to cause hepatitis, we find TDAV is capable of efficient parenteral transmission, engendering acute and chronic infections associated with a diversity of clinical presentations ranging from subclinical infection to clinical hepatitis.

  10. M-MRAC Backstepping for Systems with Unknown Virtual Control Coefficients

    NASA Technical Reports Server (NTRS)

    Stepanyan, Vahram; Krishnakumar, Kalmanje

    2015-01-01

    The paper presents an over-parametrization free certainty equivalence state feedback backstepping adaptive control design method for systems of any relative degree with unmatched uncertainties and unknown virtual control coefficients. It uses a fast prediction model to estimate the unknown parameters, which is independent of the control design. It is shown that the system's input and output tracking errors can be systematically decreased by the proper choice of the design parameters. The benefits of the approach are demonstrated in numerical simulations.

  11. Adaptive Incentive Controls for Stackelberg Games with Unknown Cost Functionals.

    DTIC Science & Technology

    1984-01-01

    APR EZT:: F I AN 73S e OsL:-: UNCLASSI?:-- Q4~.’~- .A.., 6, *~*i i~~*~~*.- U ADAPTIVE INCENTIVE CONTROLS FOR STACKELBERG GAMES WITH UNKNOWN COST...AD-A161 885 ADAPTIVE INCENTIVE CONTROLS FOR STACKELBERG GAMES WITH i/1 UNKNOWN COST FUNCTIONALSCU) ILLINOIS UNIV AT URBANA DECISION AND CONTROL LAB T...ORGANIZATION 6b. OFFICE SYMBOL 7.. NAME OF MONITORING ORGANIZATION CoriaeLcenef~pda~ Joint Services Electronics Program Laboratory, Univ. of Illinois N/A

  12. Exploiting fine-scale genetic and physiological variation of closely related microbes to reveal unknown enzyme functions.

    PubMed

    Badur, Ahmet H; Plutz, Matthew J; Yalamanchili, Geethika; Jagtap, Sujit Sadashiv; Schweder, Thomas; Unfried, Frank; Markert, Stephanie; Polz, Martin F; Hehemann, Jan-Hendrik; Rao, Christopher V

    2017-08-04

    Polysaccharide degradation by marine microbes represents one of the largest and most rapid heterotrophic transformations of organic matter in the environment. Microbes employ systems of complementary carbohydrate-specific enzymes to deconstruct algal or plant polysaccharides (glycans) into monosaccharides. Because of the high diversity of glycan substrates, the functions of these enzymes are often difficult to establish. One solution to this problem may lie within naturally occurring microdiversity; varying numbers of enzymes, due to gene loss, duplication, or transfer, among closely related environmental microbes create metabolic differences akin to those generated by knock-out strains engineered in the laboratory used to establish the functions of unknown genes. Inspired by this natural fine-scale microbial diversity, we show here that it can be used to develop hypotheses guiding biochemical experiments for establishing the role of these enzymes in nature. In this work, we investigated alginate degradation among closely related strains of the marine bacterium Vibrio splendidus One strain, V. splendidus 13B01, exhibited high extracellular alginate lyase activity compared with other V. splendidus strains. To identify the enzymes responsible for this high extracellular activity, we compared V. splendidus 13B01 with the previously characterized V. splendidus 12B01, which has low extracellular activity and lacks two alginate lyase genes present in V. splendidus 13B01. Using a combination of genomics, proteomics, biochemical, and functional screening, we identified a polysaccharide lyase family 7 enzyme that is unique to V. splendidus 13B01, secreted, and responsible for the rapid digestion of extracellular alginate. These results demonstrate the value of querying the enzymatic repertoires of closely related microbes to rapidly pinpoint key proteins with beneficial functions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. A genome-wide loss-of-function screen identifies SLC26A2 as a novel mediator of TRAIL resistance

    PubMed Central

    Dimberg, Lina Y.; Towers, Christina G.; Behbakht, Kian; Hotz, Taylor J.; Kim, Jihye; Fosmire, Susan; Porter, Christopher C.; Tan, Aik-Choon; Thorburn, Andrew; Ford, Heide L.

    2017-01-01

    TNF-related apoptosis inducing ligand (TRAIL) is a potent death-inducing ligand that mediates apoptosis through the extrinsic pathway and serves as an important endogenous tumor suppressor mechanism. Because tumor cells are often killed by TRAIL and normal cells are not, drugs that activate the TRAIL pathway have been thought to have potential clinical value. However, to date, most TRAIL-related clinical trials have largely failed due to the tumor cells having intrinsic or acquired resistance to TRAIL-induced apoptosis. Previous studies to identify resistance mechanisms have focused on targeted analysis of the canonical apoptosis pathway and other known regulators of TRAIL receptor signaling. To identify novel mechanisms of TRAIL resistance in an unbiased way, we performed a genome wide shRNA screen for genes that regulate TRAIL sensitivity in sub-lines that had been selected for acquired TRAIL resistance. This screen identified previously unknown mediators of TRAIL resistance including Angiotensin II Receptor 2, Crk-like protein, T-Box Transcription Factor 2 and solute carrier family 26 member 2 (SLC26A2). SLC26A2 downregulates the TRAIL receptors, DR4 and DR5, and this downregulation is associated with resistance to TRAIL. Its expression is high in numerous tumor types compared to normal cells, and in breast cancer, SLC26A2 is associated with a significant decrease in relapse free survival. PMID:28108622

  14. Half-blind remote sensing image restoration with partly unknown degradation

    NASA Astrophysics Data System (ADS)

    Xie, Meihua; Yan, Fengxia

    2017-01-01

    The problem of image restoration has been extensively studied for its practical importance and theoretical interest. This paper mainly discusses the problem of image restoration with partly unknown kernel. In this model, the degraded kernel function is known but its parameters are unknown. With this model, we should estimate the parameters in Gaussian kernel and the real image simultaneity. For this new problem, a total variation restoration model is put out and an intersect direction iteration algorithm is designed. Peak Signal to Noise Ratio (PSNR) and Structural Similarity Index Measurement (SSIM) are used to measure the performance of the method. Numerical results show that we can estimate the parameters in kernel accurately, and the new method has both much higher PSNR and much higher SSIM than the expectation maximization (EM) method in many cases. In addition, the accuracy of estimation is not sensitive to noise. Furthermore, even though the support of the kernel is unknown, we can also use this method to get accurate estimation.

  15. Using Functional Signature Ontology (FUSION) to Identify Mechanisms of Action for Natural Products

    PubMed Central

    Potts, Malia B.; Kim, Hyun Seok; Fisher, Kurt W.; Hu, Youcai; Carrasco, Yazmin P.; Bulut, Gamze Betul; Ou, Yi-Hung; Herrera-Herrera, Mireya L.; Cubillos, Federico; Mendiratta, Saurabh; Xiao, Guanghua; Hofree, Matan; Ideker, Trey; Xie, Yang; Huang, Lily Jun-shen; Lewis, Robert E.; MacMillan, John B.; White, Michael A.

    2014-01-01

    A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, we developed a new marine-derived, renewable natural products resource and a method for linking bioactive derivatives of this library to the proteins and biological processes that they target in cells. We used cell-based screening and computational analysis to match gene expression signatures produced by natural products to those produced by siRNA and synthetic microRNA libraries. With this strategy, we matched proteins and microRNAs with diverse biological processes and also identified putative protein targets and mechanisms of action for several previously undescribed marine-derived natural products. We confirmed mechanistic relationships for selected short-interfering RNAs, microRNAs, and compounds with functional roles in autophagy, chemotaxis mediated by discoidin domain receptor 2, or activation of the kinase AKT. Thus, this approach may be an effective method for screening new drugs while simultaneously identifying their targets. PMID:24129700

  16. Population-Based Prevalence of Intellectual Disability and Autism Spectrum Disorders in Western Australia: A Comparison With Previous Estimates.

    PubMed

    Bourke, Jenny; de Klerk, Nick; Smith, Timothy; Leonard, Helen

    2016-05-01

    To investigate the prevalence of intellectual disability (ID) and/or autism spectrum disorders (ASDs) in Western Australia (WA).A cohort of children born from 1983 to 2010 in WA with an ID and/or ASD were identified using the population-based IDEA (Intellectual Disability Exploring Answers) database, which ascertains cases through the Disability Services Commission (DSC) as well as education sources. Information on race, gender, mother's residence at birth and deaths was obtained through linkage to the Midwives Notification System and the Mortality Register. Diagnostic information on the cause of ID was obtained through review of medical records where available and children were classified as biomedical cause, ASD, or unknown cause.An overall prevalence of ID of 17.0/1000 livebirths (95% CI: 16.7, 17.4) showed an increase from the 10-year previous prevalence of 14.3/1000. The prevalence for mild or moderate ID was 15.0 (95% CI: 14.6, 15.3), severe ID was 1.2 (95% CI: 1.1, 1.3), and unknown level of ID was 0.9 (95% CI: 0.8, 1.0)/1000 livebirths. The prevalence for Aboriginal children was 39.0/1000 compared with 15.7/1000 for non-Aboriginal children, giving a prevalence ratio of 2.5 (95% CI: 2.4, 2.6). Prevalence of all ASD was 5.1/1000 of which 3.8/1000 had ASD and ID.The prevalence of ID has risen in WA over the last 10 years with most of this increase due to mild or moderate ID. Whilst the prevalence of ASD has also increased over this time this does not fully explain the observed increase. Aboriginal children are at a 2.5-fold risk of ID but are less likely to be accessing disability services.

  17. Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

    PubMed Central

    Johnson, Ben; Lowe, Gillian C.; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A.; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J.; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula HB; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E.; Watson, Steve P.; Morgan, Neil V.

    2016-01-01

    Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. PMID:27479822

  18. A new polytopic approach for the unknown input functional observer design

    NASA Astrophysics Data System (ADS)

    Bezzaoucha, Souad; Voos, Holger; Darouach, Mohamed

    2018-03-01

    In this paper, a constructive procedure to design Functional Unknown Input Observers for nonlinear continuous time systems is proposed under the Polytopic Takagi-Sugeno framework. An equivalent representation for the nonlinear model is achieved using the sector nonlinearity transformation. Applying the Lyapunov theory and the ? attenuation, linear matrix inequalities conditions are deduced which are solved for feasibility to obtain the observer design matrices. To cope with the effect of unknown inputs, classical approach of decoupling the unknown input for the linear case is used. Both algebraic and solver-based solutions are proposed (relaxed conditions). Necessary and sufficient conditions for the existence of the functional polytopic observer are given. For both approaches, the general and particular cases (measurable premise variables, full state estimation with full and reduced order cases) are considered and it is shown that the proposed conditions correspond to the one presented for standard linear case. To illustrate the proposed theoretical results, detailed numerical simulations are presented for a Quadrotor Aerial Robots Landing and a Waste Water Treatment Plant. Both systems are highly nonlinear and represented in a T-S polytopic form with unmeasurable premise variables and unknown inputs.

  19. 17. Photographic copy of photograph. Location unknown but assumed to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. Photographic copy of photograph. Location unknown but assumed to be uper end of canal. Features no longer extant. (Source: U.S. Department of Interior. Office of Indian Affairs. Indian Irrigation service. Annual Report, Fiscal Year 1925. Vol. I, Narrative and Photographs, Irrigation District #4, California and Southern Arizona, RG 75, Entry 655, Box 28, National Archives, Washington, DC.) Photographer unknown. MAIN (TITLED FLORENCE) CANAL, WASTEWAY, SLUICEWAY, & BRIDGE, 1/26/25. - San Carlos Irrigation Project, Marin Canal, Amhurst-Hayden Dam to Picacho Reservoir, Coolidge, Pinal County, AZ

  20. Chronic kidney disease of unknown aetiology and ground-water ionicity: study based on Sri Lanka.

    PubMed

    Dharma-Wardana, M W C; Amarasiri, Sarath L; Dharmawardene, Nande; Panabokke, C R

    2015-04-01

    High incidence of chronic kidney disease of unknown aetiology (CKDU) in Sri Lanka is shown to correlate with the presence of irrigation works and rivers that bring-in 'nonpoint source' fertilizer runoff from intensely agricultural regions. We review previous attempts to link CKDU with As, Cd and other standard toxins. Those studies (e.g. the WHO-sponsored study), while providing a wealth of data, are inconclusive in regard to aetiology. Here, we present new proposals based on increased ionicity of drinking water due to fertilizer runoff into the river system, redox processes in the soil and features of 'tank'-cascades and aquifers. The consequent chronic exposure to high ionicity in drinking water is proposed to debilitate the kidney via a Hofmeister-type (i.e. protein-denaturing) mechanism.

  1. 16 CFR 303.14 - Products containing unknown fibers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., secondhand materials, textile by-products, or waste materials of unknown, and for practical purposes... the fiber content disclosure otherwise required by the Act and regulations, indicate that such product is composed of miscellaneous scraps, rags, odd lots, textile by-products, secondhand materials (in...

  2. Large mass affecting retroperitoneal great vessels: a rare presentation of a cancer of unknown primary with diagnostic dilemma and challenged surgical intervention.

    PubMed

    Stakia, Paraskevi; Lagos, Panagiotis; Gourgiotis, Stavros; Tzilalis, Vasilios D; Aloizos, Stavros; Salemis, Nikolaos S

    2009-01-01

    Cancers of unknown primary site (CUPs) consist of a clinical entity which accounts for 3-5% of all solid tumor patients. They are metastatic solid tumors whose fundamental characteristic is the absence of identifiable site of the primary tumor. We report the case of a completely asymptomatic 34-year-old man with a palpated huge mass found incidentally in the left abdomen. All the investigations were normal. During the operation, a large mass was identified 2 cm below the left renal artery which was displacing and encompassing the great retroperitoneal vessels and the left ureter. A complete resection of the mass was performed while the histological examination revealed a solitary retroperitoneal lymph node categorized as metastatic adenocarcinoma of unknown primary site. It is essential to assess the high incidence of patients with cancer who present with CUP. Early surgical excision of the metastatic lesion followed by adjuvant combination chemotherapy should be considered for patients with only a single site of malignancy.

  3. Adaptive Fault-Tolerant Control of Uncertain Nonlinear Large-Scale Systems With Unknown Dead Zone.

    PubMed

    Chen, Mou; Tao, Gang

    2016-08-01

    In this paper, an adaptive neural fault-tolerant control scheme is proposed and analyzed for a class of uncertain nonlinear large-scale systems with unknown dead zone and external disturbances. To tackle the unknown nonlinear interaction functions in the large-scale system, the radial basis function neural network (RBFNN) is employed to approximate them. To further handle the unknown approximation errors and the effects of the unknown dead zone and external disturbances, integrated as the compounded disturbances, the corresponding disturbance observers are developed for their estimations. Based on the outputs of the RBFNN and the disturbance observer, the adaptive neural fault-tolerant control scheme is designed for uncertain nonlinear large-scale systems by using a decentralized backstepping technique. The closed-loop stability of the adaptive control system is rigorously proved via Lyapunov analysis and the satisfactory tracking performance is achieved under the integrated effects of unknown dead zone, actuator fault, and unknown external disturbances. Simulation results of a mass-spring-damper system are given to illustrate the effectiveness of the proposed adaptive neural fault-tolerant control scheme for uncertain nonlinear large-scale systems.

  4. Multiple tendon ruptures of unknown etiology.

    PubMed

    Axibal, Derek P; Anderson, John G

    2013-10-01

    Tendon ruptures are common findings in foot and ankle practice. The etiology of tendon ruptures tends to be multifactorial-usually due to a combination of trauma, effects of systemic diseases, adverse effects of medications, and obesity. We present an unusual case of right Achilles tendinitis, left Achilles tendon rupture, bilateral peroneus longus tendon rupture, and left peroneus brevis tendon rupture of unknown etiology. This case report highlights the need for research for other possible, lesser known etiologies of tendon pathology. Therapeutic, Level IV, Case Study.

  5. Fever of Unknown Origin in Childhood.

    PubMed

    Chusid, Michael J

    2017-02-01

    Childhood fever of unknown origin (FUO) is most often related to an underlying infection but can also be associated with a variety of neoplastic, rheumatologic, and inflammatory conditions. Repeated, focused reviews of patient history and physical examination are often helpful in suggesting a likely diagnosis. Diagnostic workup should be staged, usually leaving invasive testing for last. Advances in molecular genetic techniques have increased the importance of these assays in the diagnosis of FUO in children. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Distinct Molecular Signature of Murine Fetal Liver and Adult Hematopoietic Stem Cells Identify Novel Regulators of Hematopoietic Stem Cell Function

    PubMed Central

    Manesia, Javed K.; Franch, Monica; Tabas-Madrid, Daniel; Nogales-Cadenas, Ruben; Vanwelden, Thomas; Van Den Bosch, Elisa; Xu, Zhuofei; Pascual-Montano, Alberto; Khurana, Satish; Verfaillie, Catherine M.

    2018-01-01

    During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA sequencing-based gene expression analysis on FL HSCs from 14.5-day mouse embryo (E14.5) in comparison to the ABM HSCs. We reanalyzed these data to identify key transcriptional regulators that play important roles in the expansion of HSCs during development. The comparison of FL E14.5 with ABM HSCs identified more than 1,400 differentially expressed genes. More than 200 genes were shortlisted based on the gene ontology (GO) annotation term “transcription.” By morpholino-based knockdown studies in zebrafish, we assessed the function of 18 of these regulators, previously not associated with HSC proliferation. Our studies identified a previously unknown role for tdg, uhrf1, uchl5, and ncoa1 in the emergence of definitive hematopoiesis in zebrafish. In conclusion, we demonstrate that identification of genes involved in transcriptional regulation differentially expressed between expanding FL HSCs and quiescent ABM HSCs, uncovers novel regulators of HSC function. PMID:27958775

  7. 48 CFR 52.222-49 - Service Contract Act-Place of Performance Unknown.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Service Contract Act-Place... Provisions and Clauses 52.222-49 Service Contract Act—Place of Performance Unknown. As prescribed in 22.1006(f), insert the following clause: Service Contract Act—Place of Performance Unknown (MAY 1989) (a...

  8. Analysis of multinomial models with unknown index using data augmentation

    USGS Publications Warehouse

    Royle, J. Andrew; Dorazio, R.M.; Link, W.A.

    2007-01-01

    Multinomial models with unknown index ('sample size') arise in many practical settings. In practice, Bayesian analysis of such models has proved difficult because the dimension of the parameter space is not fixed, being in some cases a function of the unknown index. We describe a data augmentation approach to the analysis of this class of models that provides for a generic and efficient Bayesian implementation. Under this approach, the data are augmented with all-zero detection histories. The resulting augmented dataset is modeled as a zero-inflated version of the complete-data model where an estimable zero-inflation parameter takes the place of the unknown multinomial index. Interestingly, data augmentation can be justified as being equivalent to imposing a discrete uniform prior on the multinomial index. We provide three examples involving estimating the size of an animal population, estimating the number of diabetes cases in a population using the Rasch model, and the motivating example of estimating the number of species in an animal community with latent probabilities of species occurrence and detection.

  9. New Algorithm Identifies Tidal Streams Oriented Along our Line-of-Sight

    NASA Astrophysics Data System (ADS)

    Lin, Ziyi; Newberg, Heidi; Amy, Paul; Martin, Charles Harold; Rockcliffe, Keighley E.

    2018-01-01

    The known dwarf galaxy tidal streams in the Milky Way are primarily oriented perpendicular to our line-of-sight. That is because they are concentrated into an observable higher-surface-brightness feature at a particular distance, or because they tightly cluster in line-of-sight velocity in a particular direction. Streams that are oriented along our line-of-sight are spread over a large range of distances and velocities. However, these distances and velocities are correlated in predicable ways. We used a set of randomly oriented Milky Way orbits to develop a technique that bins stars in combinations of distance and velocity that are likely for tidal streams. We applied this technique to identify previously unknown tidal streams in a set of blue horizontal branch stars in the first quadrant from Data Release 10 of the Sloan Digital Sky Survey (SDSS). This project was supported by NSF grant AST 16-15688, a Rensselaer Presidential Fellowship, the NASA/NY Space Grant fellowship, and contributions made by The Marvin Clan, Babette Josephs, Manit Limlamai, and the 2015 Crowd Funding Campaign to Support Milky Way Research.

  10. Carcinoma of Unknown Primary Treatment (PDQ®)—Patient Version

    Cancer.gov

    Carcinoma of unknown primary (CUP), treatment can include surgery, radiation therapy, chemotherapy, or hormone therapy. Get detailed information about the diagnosis and treatment of CUP in this expert-reviewed summary.

  11. Unified sensor management in unknown dynamic clutter

    NASA Astrophysics Data System (ADS)

    Mahler, Ronald; El-Fallah, Adel

    2010-04-01

    In recent years the first author has developed a unified, computationally tractable approach to multisensor-multitarget sensor management. This approach consists of closed-loop recursion of a PHD or CPHD filter with maximization of a "natural" sensor management objective function called PENT (posterior expected number of targets). In this paper we extend this approach so that it can be used in unknown, dynamic clutter backgrounds.

  12. Hazardous-waste-characterization survey of unknown drums at the 21st Tactical Fighter Wing, Elmendorf and Shemya Air Force Bases, and Galena and King Salmon Airports, Alaska. Final report 2-13 Aug 91

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

    Bishop, M.S.

    1991-12-01

    At the request of the USAF Regional Hospital Elmendorf/SGPB (PACAF), the Armstrong Laboratory, Occupational and Environmental Health Directorate, conducted a hazardous waste characterization survey of unknown drums at Elmendorf AFB from 2 Aug - 13 Aug 91. The scope of the survey was to sample and characterize drums of unknown material stored at Elmendorf AFB, Shemya AFB, and Galena and King Salmon Airports. Several waste streams were sampled at Elmendorf AFB to revalidate sample results from a previous survey.

  13. Atmospheric turbulence profiling with unknown power spectral density

    NASA Astrophysics Data System (ADS)

    Helin, Tapio; Kindermann, Stefan; Lehtonen, Jonatan; Ramlau, Ronny

    2018-04-01

    Adaptive optics (AO) is a technology in modern ground-based optical telescopes to compensate for the wavefront distortions caused by atmospheric turbulence. One method that allows to retrieve information about the atmosphere from telescope data is so-called SLODAR, where the atmospheric turbulence profile is estimated based on correlation data of Shack-Hartmann wavefront measurements. This approach relies on a layered Kolmogorov turbulence model. In this article, we propose a novel extension of the SLODAR concept by including a general non-Kolmogorov turbulence layer close to the ground with an unknown power spectral density. We prove that the joint estimation problem of the turbulence profile above ground simultaneously with the unknown power spectral density at the ground is ill-posed and propose three numerical reconstruction methods. We demonstrate by numerical simulations that our methods lead to substantial improvements in the turbulence profile reconstruction compared to the standard SLODAR-type approach. Also, our methods can accurately locate local perturbations in non-Kolmogorov power spectral densities.

  14. Learned navigation in unknown terrains: A retraction method

    NASA Technical Reports Server (NTRS)

    Rao, Nageswara S. V.; Stoltzfus, N.; Iyengar, S. Sitharama

    1989-01-01

    The problem of learned navigation of a circular robot R, of radius delta (is greater than or equal to 0), through a terrain whose model is not a-priori known is considered. Two-dimensional finite-sized terrains populated by an unknown (but, finite) number of simple polygonal obstacles are also considered. The number and locations of the vertices of each obstacle are unknown to R. R is equipped with a sensor system that detects all vertices and edges that are visible from its present location. In this context two problems are covered. In the visit problem, the robot is required to visit a sequence of destination points, and in the terrain model acquisition problem, the robot is required to acquire the complete model of the terrain. An algorithmic framework is presented for solving these two problems using a retraction of the freespace onto the Voronoi diagram of the terrain. Algorithms are then presented to solve the visit problem and the terrain model acquisition problem.

  15. [Metastasis revealing malignant peritoneum mesothelioma: About the difficulty to identify the primary tumors].

    PubMed

    Bretagne, Charles-Henri; Petitjean, Alain; Felix, Sophie; Bedgedjian, Isabelle; Algros, Marie-Paule; Delabrousse, Eric; Valmary-Degano, Séverine

    2016-04-01

    Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology

    PubMed Central

    Michael, Benedict D.; Griffiths, Michael J.; Granerod, Julia; Brown, David; Davies, Nicholas W. S.; Borrow, Ray; Solomon, Tom

    2016-01-01

    Background Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15–60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. Methods We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Results Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Conclusions Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation. PMID:26808276

  17. Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.

    PubMed

    Michael, Benedict D; Griffiths, Michael J; Granerod, Julia; Brown, David; Davies, Nicholas W S; Borrow, Ray; Solomon, Tom

    2016-01-01

    Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.

  18. Dealing with Unknown Variables in Policy/Program Evaluation.

    ERIC Educational Resources Information Center

    Nagel, Stuart S.

    1983-01-01

    Threshold analysis (TA) is introduced as an evaluation model. TA converts unknown variables into questions as to whether a given benefit, cost, or success probability is more or less than a threshold, above which the proposed project would be profitable, and below which it would be unprofitable. (Author/PN)

  19. Part 2. Development of Enhanced Statistical Methods for Assessing Health Effects Associated with an Unknown Number of Major Sources of Multiple Air Pollutants.

    PubMed

    Park, Eun Sug; Symanski, Elaine; Han, Daikwon; Spiegelman, Clifford

    2015-06-01

    A major difficulty with assessing source-specific health effects is that source-specific exposures cannot be measured directly; rather, they need to be estimated by a source-apportionment method such as multivariate receptor modeling. The uncertainty in source apportionment (uncertainty in source-specific exposure estimates and model uncertainty due to the unknown number of sources and identifiability conditions) has been largely ignored in previous studies. Also, spatial dependence of multipollutant data collected from multiple monitoring sites has not yet been incorporated into multivariate receptor modeling. The objectives of this project are (1) to develop a multipollutant approach that incorporates both sources of uncertainty in source-apportionment into the assessment of source-specific health effects and (2) to develop enhanced multivariate receptor models that can account for spatial correlations in the multipollutant data collected from multiple sites. We employed a Bayesian hierarchical modeling framework consisting of multivariate receptor models, health-effects models, and a hierarchical model on latent source contributions. For the health model, we focused on the time-series design in this project. Each combination of number of sources and identifiability conditions (additional constraints on model parameters) defines a different model. We built a set of plausible models with extensive exploratory data analyses and with information from previous studies, and then computed posterior model probability to estimate model uncertainty. Parameter estimation and model uncertainty estimation were implemented simultaneously by Markov chain Monte Carlo (MCMC*) methods. We validated the methods using simulated data. We illustrated the methods using PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter) speciation data and mortality data from Phoenix, Arizona, and Houston, Texas. The Phoenix data included counts of cardiovascular deaths and daily PM2

  20. Structural identifiability of cyclic graphical models of biological networks with latent variables.

    PubMed

    Wang, Yulin; Lu, Na; Miao, Hongyu

    2016-06-13

    Graphical models have long been used to describe biological networks for a variety of important tasks such as the determination of key biological parameters, and the structure of graphical model ultimately determines whether such unknown parameters can be unambiguously obtained from experimental observations (i.e., the identifiability problem). Limited by resources or technical capacities, complex biological networks are usually partially observed in experiment, which thus introduces latent variables into the corresponding graphical models. A number of previous studies have tackled the parameter identifiability problem for graphical models such as linear structural equation models (SEMs) with or without latent variables. However, the limited resolution and efficiency of existing approaches necessarily calls for further development of novel structural identifiability analysis algorithms. An efficient structural identifiability analysis algorithm is developed in this study for a broad range of network structures. The proposed method adopts the Wright's path coefficient method to generate identifiability equations in forms of symbolic polynomials, and then converts these symbolic equations to binary matrices (called identifiability matrix). Several matrix operations are introduced for identifiability matrix reduction with system equivalency maintained. Based on the reduced identifiability matrices, the structural identifiability of each parameter is determined. A number of benchmark models are used to verify the validity of the proposed approach. Finally, the network module for influenza A virus replication is employed as a real example to illustrate the application of the proposed approach in practice. The proposed approach can deal with cyclic networks with latent variables. The key advantage is that it intentionally avoids symbolic computation and is thus highly efficient. Also, this method is capable of determining the identifiability of each single parameter and

  1. An epidemiological study of risk factors associated with the recurrence of equine grass sickness (dysautonomia) on previously affected premises.

    PubMed

    Newton, J R; Hedderson, E J; Adams, V J; McGorum, B C; Proudman, C J; Wood, J L N

    2004-03-01

    The reasons why equine grass sickness (EGS) recurs on premises are unknown and, consequently, practical methods for reducing the risk of recurrence are not available. To identify risk factors associated with recurrence of EGS on premises and to gain possible insights into the pathogenesis of the disease. Data on disease history and risk factors were collected by postal questionnaire from premises with EGS cases between 1st January 1997 and 31st December 2001. Data on variation in rates of recurrence of EGS for different risk factors were analysed using Poisson regression analysis. Of 509 premises contacted, 305 (60%) returned useable questionnaires and 100 of these (33%) were classified as 'recurrent' premises. An overall median incidence rate for EGS of 2.1 EGS incidents/100 horses/premises/year was recorded. There was an increased rate of recurrence with higher numbers of horses, presence of younger animals, stud farms and livery/riding establishments, loam and sand soils, rearing of domestic birds and mechanical droppings removal. The rate of recurrence decreased with chalk soil, cograzing ruminants, grass cutting on pastures and removal of droppings by hand. Several statistically significant interactions were identified. Many of the findings are consistent with the theory that EGS is a toxico-infectious form of botulism. Several of the significant factors identified may directly or indirectly relate to soil disturbance and consequent soil contamination of grass, thereby increasing the rate of exposure of grazing horses to Clostridium botulinum, which resides in soil. Identification of potentially modifiable risk factors may, ideally following validation in appropriately designed, controlled and randomised intervention studies, lead to practical measures to reduce the incidence of EGS on previously affected premises.

  2. Cervical lymph node metastases of squamous cell carcinoma of unknown origin: the diagnostic value of FDG PET/CT and clinical outcome.

    PubMed

    Dale, Einar; Moan, Jon M; Osnes, Terje A; Bogsrud, Trond V

    2017-02-01

    FDG PET/CT is perceived as a valuable diagnostic tool in addition to the standard diagnostic workup for patients with isolated neck lymph nodes of squamous cell carcinoma of unknown primary (SCCUP). For patients with SCCUP intended for primary radiotherapy, we hypothesize that the previously reported FDG PET/CT detection rates are too high. From 2008 to 2015, 30 SCCUP patients were examined with FDG PET/CT. The objective of the FDG PET/CT examination was twofold: (1) improve the radiotherapy target definition, and (2) identify the primary cancer. Before the FDG PET/CT, the patients had been through a standard workup consisting of CT of the neck and chest, examination with flexible endoscopy with patient awake, panendoscopy and examination under general anesthesia, tonsillectomy and sometimes blind sampling biopsies, and MRI (floor of the mouth). All FDG PET/CTs were performed applying a flat table, head support and fixation mask as part of the radiotherapy treatment planning. Diagnostic CT with contrast was an integrated part of the PET/CT examination. Only 1/30 patients (cancer of the vallecula) had their primary cancer detected by FDG PET/CT. In addition, a non-biopsied patient with high uptake in the ipsilateral palatine tonsil was included, giving a detection rate of ≤7 % (95 % CI 2-21 %). In this retrospective study, we found that the FDG PET/CT detection rate of the primary for SCCUP patients is lower than previously reported. It is questionable whether FDG PET/CT is necessary for these patients when improved, advanced workup is available.

  3. Transcriptomic Analysis in a Drosophila Model Identifies Previously Implicated and Novel Pathways in the Therapeutic Mechanism in Neuropsychiatric Disorders

    PubMed Central

    Singh, Priyanka; Mohammad, Farhan; Sharma, Abhay

    2011-01-01

    We have taken advantage of a newly described Drosophila model to gain insights into the potential mechanism of antiepileptic drugs (AEDs), a group of drugs that are widely used in the treatment of several neurological and psychiatric conditions besides epilepsy. In the recently described Drosophila model that is inspired by pentylenetetrazole (PTZ) induced kindling epileptogenesis in rodents, chronic PTZ treatment for 7 days causes a decreased climbing speed and an altered CNS transcriptome, with the latter mimicking gene expression alterations reported in epileptogenesis. In the model, an increased climbing speed is further observed 7 days after withdrawal from chronic PTZ. We used this post-PTZ withdrawal regime to identify potential AED mechanism. In this regime, treatment with each of the five AEDs tested, namely, ethosuximide, gabapentin, vigabatrin, sodium valproate, and levetiracetam, resulted in rescuing of the altered climbing behavior. The AEDs also normalized PTZ withdrawal induced transcriptomic perturbation in fly heads; whereas AED untreated flies showed a large number of up- and down-regulated genes which were enriched in several processes including gene expression and cell communication, the AED treated flies showed differential expression of only a small number of genes that did not enrich gene expression and cell communication processes. Gene expression and cell communication related upregulated genes in AED untreated flies overrepresented several pathways – spliceosome, RNA degradation, and ribosome in the former category, and inositol phosphate metabolism, phosphatidylinositol signaling, endocytosis, and hedgehog signaling in the latter. Transcriptome remodeling effect of AEDs was overall confirmed by microarray clustering that clearly separated the profiles of AED treated and untreated flies. Besides being consistent with previously implicated pathways, our results provide evidence for a role of other pathways in psychiatric drug

  4. Genetics Experts Unite to I.D. Unknown Katrina Victims

    MedlinePlus

    ... News From NIH Genetics Experts Unite to I.D. Unknown Katrina Victims Past Issues / Summer 2006 Table ... and genetics," says team member Stephen Sherry, Ph.D., of NLM's National Center for Biotechnology Information, "is ...

  5. Dynamic Modeling from Flight Data with Unknown Time Skews

    NASA Technical Reports Server (NTRS)

    Morelli, Eugene A.

    2016-01-01

    A method for estimating dynamic model parameters from flight data with unknown time skews is described and demonstrated. The method combines data reconstruction, nonlinear optimization, and equation-error parameter estimation in the frequency domain to accurately estimate both dynamic model parameters and the relative time skews in the data. Data from a nonlinear F-16 aircraft simulation with realistic noise, instrumentation errors, and arbitrary time skews were used to demonstrate the approach. The approach was further evaluated using flight data from a subscale jet transport aircraft, where the measured data were known to have relative time skews. Comparison of modeling results obtained from time-skewed and time-synchronized data showed that the method accurately estimates both dynamic model parameters and relative time skew parameters from flight data with unknown time skews.

  6. Comparative glycoproteomics of stem cells identifies new players in ricin toxicity.

    PubMed

    Stadlmann, Johannes; Taubenschmid, Jasmin; Wenzel, Daniel; Gattinger, Anna; Dürnberger, Gerhard; Dusberger, Frederico; Elling, Ulrich; Mach, Lukas; Mechtler, Karl; Penninger, Josef M

    2017-09-28

    Glycosylation, the covalent attachment of carbohydrate structures onto proteins, is the most abundant post-translational modification. Over 50% of human proteins are glycosylated, which alters their activities in diverse fundamental biological processes. Despite the importance of glycosylation in biology, the identification and functional validation of complex glycoproteins has remained largely unexplored. Here we develop a novel quantitative approach to identify intact glycopeptides from comparative proteomic data sets, allowing us not only to infer complex glycan structures but also to directly map them to sites within the associated proteins at the proteome scale. We apply this method to human and mouse embryonic stem cells to illuminate the stem cell glycoproteome. This analysis nearly doubles the number of experimentally confirmed glycoproteins, identifies previously unknown glycosylation sites and multiple glycosylated stemness factors, and uncovers evolutionarily conserved as well as species-specific glycoproteins in embryonic stem cells. The specificity of our method is confirmed using sister stem cells carrying repairable mutations in enzymes required for fucosylation, Fut9 and Slc35c1. Ablation of fucosylation confers resistance to the bioweapon ricin, and we discover proteins that carry a fucosylation-dependent sugar code for ricin toxicity. Mutations disrupting a subset of these proteins render cells ricin resistant, revealing new players that orchestrate ricin toxicity. Our comparative glycoproteomics platform, SugarQb, enables genome-wide insights into protein glycosylation and glycan modifications in complex biological systems.

  7. A new commelinid monocot seed fossil from the early Eocene previously identified as Solanaceae.

    PubMed

    Särkinen, Tiina; Kottner, Sören; Stuppy, Wolfgang; Ahmed, Farah; Knapp, Sandra

    2018-01-01

    Fossils provide minimum age estimates for extant lineages. Here we critically evaluate Cantisolanum daturoides Reid & Chandler and two other early putative seed fossils of Solanaceae, an economically important plant family in the Asteridae. Three earliest seed fossil taxa of Solanaceae from the London Clay Formation (Cantisolanum daturoides) and the Poole and Branksome Sand Formations (Solanum arnense Chandler and Solanispermum reniforme Chandler) were studied using x-ray microcomputed tomography (MCT) and scanning electron microscopy (SEM). The MCT scans of Cantisolanum daturoides revealed a high level of pyrite preservation at the cellular level. Cantisolanum daturoides can be clearly excluded from Solanaceae and has more affinities to the commelinid monocots based on a straight longitudinal axis, a prominent single layer of relatively thin-walled cells in the testa, and a clearly differentiated micropyle surrounded by radially elongated and inwardly curved testal cells. While the MCT scans show no internal preservation in Solanum arnense and Solanispermum reniforme, SEM images show the presence of several characteristics that allow the placement of these taxa at the stem node of Solanaceae. Cantisolanum daturoides is likely a member of commelinid monocots and not Solanaceae as previously suggested. The earliest fossil record of Solanaceae is revised to consist of fruit fossil with inflated calyces from the early Eocene of Patagonia (52 Ma) and fossilized seeds from the early to mid-Eocene of Europe (48-46 Ma). The new identity for Cantisolanum daturoides does not alter a late Cretaceous minimum age for commelinids. © 2018 Botanical Society of America.

  8. Identifying OH Imposters in the ALFALFA HI Survey

    NASA Astrophysics Data System (ADS)

    Suess, Katherine; Darling, Jeremiah K.; Haynes, Martha P.; Giovanelli, Riccardo

    2015-01-01

    OH megamasers (OHMs) are rare, luminous molecular masers that are typically observed in (ultra) luminous infrared galaxies and serve as markers of major galaxy mergers. In blind emission line surveys such as the ALFALFA (Arecibo Legacy Fast Arecibo L-Band Feed Array) survey for neutral hydrogen (HI) in the local universe, OHMs at z~0.2 can mimic z~0.05 HI lines. We present the results of optical spectroscopy of ambiguous HI detections in the ALFALFA 40% data release [1] detected by WISE but with uncertain optical counterparts. The optical redshifts, obtained from observations at the Apache Point Observatory 3.5m telescope, identified 127 HI optical counterparts and discovered five new OHMs. Fifty-six candidates remain ambiguous. The new OHMs are the first detected in a blind spectral line survey.The number of OHMs in ALFALFA matches predictions based on the OH luminosity function [2]. Additionally, the OHMs found in a blind survey do not seem to differ from those found in previous targeted surveys. This provides validation of the methods used in previous IR-selected OHM surveys and indicates there is no previously unknown OHM-producing population at z~0.2. We also provide a method for future surveys to separate OH and HI lines without expensive spectral observations. This method utilizes infrared colors and magnitudes, such as WISE mid-IR data. Since the fraction of OHMs found in flux-limited HI surveys is expected to increase with the redshift of the survey [3], this analysis can be applied to future flux-limited high-redshift hydrogen surveys.We thank the ALFALFA team for observing and producing the survey dataset. The ALFALFA team at Cornell is supported by NSF AST-1107390 and the Brinson Foundation.[1] Haynes, M. P., R. Giovanelli, A. M. Martin, K. M. Hess, A. Saintonge, et al. 2011, Astron J, 142, 142[2] Darling, J. & R. Giovanelli 2002, Astrophys J, 572, 810[3] Briggs, F. H. 1998, A&A, 336, 815

  9. Design of a DNA chip for detection of unknown genetically modified organisms (GMOs).

    PubMed

    Nesvold, Håvard; Kristoffersen, Anja Bråthen; Holst-Jensen, Arne; Berdal, Knut G

    2005-05-01

    Unknown genetically modified organisms (GMOs) have not undergone a risk evaluation, and hence might pose a danger to health and environment. There are, today, no methods for detecting unknown GMOs. In this paper we propose a novel method intended as a first step in an approach for detecting unknown genetically modified (GM) material in a single plant. A model is designed where biological and combinatorial reduction rules are applied to a set of DNA chip probes containing all possible sequences of uniform length n, creating probes capable of detecting unknown GMOs. The model is theoretically tested for Arabidopsis thaliana Columbia, and the probabilities for detecting inserts and receiving false positives are assessed for various parameters for this organism. From a theoretical standpoint, the model looks very promising but should be tested further in the laboratory. The model and algorithms will be available upon request to the corresponding author.

  10. Merkel Cell Carcinoma of Unknown Primary Origin

    PubMed Central

    Deneve, Jeremiah L.; Messina, Jane L.; Marzban, Suroosh S.; Gonzalez, Ricardo J.; Walls, Brooke M.; Fisher, Kate J.; Ann Chen, Y.; Wayne Cruse, C.; Sondak, Vernon K.; Zager, Jonathan S.

    2015-01-01

    Background Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes. Methods After institutional review board approval, our institutional database spanning the years 1998–2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed. Results From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months. Conclusions Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients. PMID:22271206

  11. Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs

    PubMed Central

    Jima, Dereje D.; Zhang, Jenny; Jacobs, Cassandra; Richards, Kristy L.; Dunphy, Cherie H.; Choi, William W. L.; Yan Au, Wing; Srivastava, Gopesh; Czader, Magdalena B.; Rizzieri, David A.; Lagoo, Anand S.; Lugar, Patricia L.; Mann, Karen P.; Flowers, Christopher R.; Bernal-Mizrachi, Leon; Naresh, Kikkeri N.; Evens, Andrew M.; Gordon, Leo I.; Luftig, Micah; Friedman, Daphne R.; Weinberg, J. Brice; Thompson, Michael A.; Gill, Javed I.; Liu, Qingquan; How, Tam; Grubor, Vladimir; Gao, Yuan; Patel, Amee; Wu, Han; Zhu, Jun; Blobe, Gerard C.; Lipsky, Peter E.; Chadburn, Amy

    2010-01-01

    A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-β pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions. PMID:20733160

  12. Metastatic Neuroendocrine Carcinoma of Unknown Origin Arising in the Femoral Nerve Sheath.

    PubMed

    Candy, Nicholas; Young, Adam; Allinson, Kieren; Carr, Oliver; McMillen, Jason; Trivedi, Rikin

    2017-08-01

    Metastatic neuroendocrine carcinoma of unknown origin is a rare condition, usually presenting with lesions in the liver and/or lung. We present the first reported case of a metastatic neuroendocrine carcinoma of unknown origin arising in the femoral nerve sheath. Magnetic resonance imaging demonstrated what was thought to be a schwannoma in the left femoral nerve sheath in the proximal femoral triangle, immediately inferior to the anterior inferior iliac spine. At the time of operation, the tumor capsule was invading surrounding tissue, as well as three trunks of the femoral nerve. The patient underwent a subtotal resection, preserving the integrity of the residual functioning femoral nerve trunks. Histologic evaluation determined that the tumor had features consistent with a metastatic neuroendocrine carcinoma of unknown primary origin. The patient recovered well postoperatively, and subsequent radiologic evaluation failed to demonstrate a potential primary site. Unfortunately, the patient re-presented with disease progression and was subsequently referred to palliative care. We recommend that there is a definite role for surgery in the management of solitary neuroendocrine carcinoma of unknown origin. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects.

    PubMed

    Johnson, Ben; Lowe, Gillian C; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula Hb; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E; Watson, Steve P; Morgan, Neil V

    2016-10-01

    Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×10 9 /L to 186×10 9 /L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified "pathogenic" or "likely pathogenic" variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. Copyright© Ferrata Storti Foundation.

  14. Squamous cell carcinoma presenting with trigeminal anesthesia: An uncommon presentation of head & neck cancer with unknown primary.

    PubMed

    Shah, Ameer T; Dagher, Walid I; O'Leary, Miriam A; Wein, Richard O

    The differential diagnosis of facial anesthesia is vast. This may be secondary to trauma, neoplasm, both intracranial and extracranial, infection, and neurologic disease. When evaluating a patient with isolated facial anesthesia, the head and neck surgeon often thinks of adenoid cystic carcinoma, which has a propensity for perineural invasion and spread. When one thinks of head and neck squamous cell carcinoma with or without unknown primary, the typical presentation involves dysphagia, odynophagia, weight loss, hoarseness, or more commonly, a neck mass. Squamous cell carcinoma presenting as facial anesthesia and perineural spread, with no primary site is quite rare. Case presentations and review of the literature. Trigeminal anesthesia is an uncommon presentation of head and neck squamous cell carcinoma with unknown primary. We present two interesting cases of invasive squamous cell carcinoma of the trigeminal nerve, with no primary site identified. We will also review the literature of head and neck malignancies with perineural spread and the management techniques for the two different cases presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Online Solution of Two-Player Zero-Sum Games for Continuous-Time Nonlinear Systems With Completely Unknown Dynamics.

    PubMed

    Fu, Yue; Chai, Tianyou

    2016-12-01

    Regarding two-player zero-sum games of continuous-time nonlinear systems with completely unknown dynamics, this paper presents an online adaptive algorithm for learning the Nash equilibrium solution, i.e., the optimal policy pair. First, for known systems, the simultaneous policy updating algorithm (SPUA) is reviewed. A new analytical method to prove the convergence is presented. Then, based on the SPUA, without using a priori knowledge of any system dynamics, an online algorithm is proposed to simultaneously learn in real time either the minimal nonnegative solution of the Hamilton-Jacobi-Isaacs (HJI) equation or the generalized algebraic Riccati equation for linear systems as a special case, along with the optimal policy pair. The approximate solution to the HJI equation and the admissible policy pair is reexpressed by the approximation theorem. The unknown constants or weights of each are identified simultaneously by resorting to the recursive least square method. The convergence of the online algorithm to the optimal solutions is provided. A practical online algorithm is also developed. Simulation results illustrate the effectiveness of the proposed method.

  16. Impact of Accurate 30-Day Status on Operative Mortality: Wanted Dead or Alive, Not Unknown.

    PubMed

    Ring, W Steves; Edgerton, James R; Herbert, Morley; Prince, Syma; Knoff, Cathy; Jenkins, Kristin M; Jessen, Michael E; Hamman, Baron L

    2017-12-01

    Risk-adjusted operative mortality is the most important quality metric in cardiac surgery for determining The Society of Thoracic Surgeons (STS) Composite Score for star ratings. Accurate 30-day status is required to determine STS operative mortality. The goal of this study was to determine the effect of unknown or missing 30-day status on risk-adjusted operative mortality in a regional STS Adult Cardiac Surgery Database cooperative and demonstrate the ability to correct these deficiencies by matching with an administrative database. STS Adult Cardiac Surgery Database data were submitted by 27 hospitals from five hospital systems to the Texas Quality Initiative (TQI), a regional quality collaborative. TQI data were matched with a regional hospital claims database to resolve unknown 30-day status. The risk-adjusted operative mortality observed-to-expected (O/E) ratio was determined before and after matching to determine the effect of unknown status on the operative mortality O/E. TQI found an excessive (22%) unknown 30-day status for STS isolated coronary artery bypass grafting cases. Matching the TQI data to the administrative claims database reduced the unknowns to 7%. The STS process of imputing unknown 30-day status as alive underestimates the true operative mortality O/E (1.27 before vs 1.30 after match), while excluding unknowns overestimates the operative mortality O/E (1.57 before vs 1.37 after match) for isolated coronary artery bypass grafting. The current STS algorithm of imputing unknown 30-day status as alive and a strategy of excluding cases with unknown 30-day status both result in erroneous calculation of operative mortality and operative mortality O/E. However, external validation by matching with an administrative database can improve the accuracy of clinical databases such as the STS Adult Cardiac Surgery Database. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Red Pine Pocket Mortality - Unknown Cause (Pest Alert)

    Treesearch

    USDA Forest Service

    1985-01-01

    Continuing mortality of red pine from an unknown cause has been observed in 30 to 40 year old plantations in southern and west central Wisconsin. A single tree or small group of trees die, followed by mortality of adjacent trees. These circular pockets of dead trees expand up to 0.3 acre per year.

  18. Application of incremental unknowns to the Burgers equation

    NASA Technical Reports Server (NTRS)

    Choi, Haecheon; Temam, Roger

    1993-01-01

    In this article, we make a few remarks on the role that attractors and inertial manifolds play in fluid mechanics problems. We then describe the role of incremental unknowns for approximating attractors and inertial manifolds when finite difference multigrid discretizations are used. The relation with direct numerical simulation and large eddy simulation is also mentioned.

  19. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

    PubMed Central

    Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

    2016-01-01

    Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome-wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo. PMID:26870082

  20. A novel prokaryotic promoter identified in the genome of some monopartite begomoviruses.

    PubMed

    Wang, Wei-Chen; Hsu, Yau-Heiu; Lin, Na-Sheng; Wu, Chia-Ying; Lai, Yi-Chin; Hu, Chung-Chi

    2013-01-01

    Geminiviruses are known to exhibit both prokaryotic and eukaryotic features in their genomes, with the ability to express their genes and even replicate in bacterial cells. We have demonstrated previously the existence of unit-length single-stranded circular DNAs of Ageratum yellow vein virus (AYVV, a species in the genus Begomovirus, family Geminiviridae) in Escherichia coli cells, which prompted our search for unknown prokaryotic functions in the begomovirus genomes. By using a promoter trapping strategy, we identified a novel prokaryotic promoter, designated AV3 promoter, in nts 762-831 of the AYVV genome. Activity assays revealed that the AV3 promoter is strong, unidirectional, and constitutive, with an endogenous downstream ribosome binding site and a translatable short open reading frame of eight amino acids. Sequence analyses suggested that the AV3 promoter might be a remnant of prokaryotic ancestors that could be related to certain promoters of bacteria from marine or freshwater environments. The discovery of the prokaryotic AV3 promoter provided further evidence for the prokaryotic origin in the evolutionary history of geminiviruses.

  1. A Novel Prokaryotic Promoter Identified in the Genome of Some Monopartite Begomoviruses

    PubMed Central

    Wang, Wei-Chen; Hsu, Yau-Heiu; Lin, Na-Sheng; Wu, Chia-Ying; Lai, Yi-Chin; Hu, Chung-Chi

    2013-01-01

    Geminiviruses are known to exhibit both prokaryotic and eukaryotic features in their genomes, with the ability to express their genes and even replicate in bacterial cells. We have demonstrated previously the existence of unit-length single-stranded circular DNAs of Ageratum yellow vein virus (AYVV, a species in the genus Begomovirus, family Geminiviridae) in Escherichia coli cells, which prompted our search for unknown prokaryotic functions in the begomovirus genomes. By using a promoter trapping strategy, we identified a novel prokaryotic promoter, designated AV3 promoter, in nts 762-831 of the AYVV genome. Activity assays revealed that the AV3 promoter is strong, unidirectional, and constitutive, with an endogenous downstream ribosome binding site and a translatable short open reading frame of eight amino acids. Sequence analyses suggested that the AV3 promoter might be a remnant of prokaryotic ancestors that could be related to certain promoters of bacteria from marine or freshwater environments. The discovery of the prokaryotic AV3 promoter provided further evidence for the prokaryotic origin in the evolutionary history of geminiviruses. PMID:23936138

  2. Intrathecal immunoglobulin synthesis in patients with symptomatic epilepsy and epilepsy of unknown etiology ('cryptogenic').

    PubMed

    Fauser, S; Soellner, C; Bien, C G; Tumani, H

    2017-09-01

    To compare the frequency of intrathecal immunoglobulin (Ig) synthesis in patients with symptomatic epilepsy and epilepsy of unknown etiology ('cryptogenic'). Patients with epileptic (n = 301) and non-epileptic (n = 10) seizures were retrospectively screened for autochthonous intrathecal Ig synthesis and oligoclonal bands (OCBs) in the cerebrospinal fluid. Intrathecal IgG/OCBs were detected in 8% of patients with epilepsies of unknown etiology, 5% of patients with first seizures of unknown cause and 0-4% of patients with epilepsy due to brain tumors, cerebrovascular disease or other etiologies. Intrathecal IgG/OCBs were not seen in patients with psychogenic seizures. Identical OCBs in serum and cerebrospinal fluid were more common in all patient groups (10-40% depending on underlying etiology). Intrathecal IgG synthesis/OCBs were observed slightly more frequently in patients with 'cryptogenic' epilepsy and with first seizures of unknown etiology than in other patient groups. However, this remained an infrequent finding and thus we could not confirm humoral immunity as a leading disease mechanism in patients with epilepsy in general or with unknown etiology in particular. © 2017 EAN.

  3. Surface ocean metabarcoding confirms limited diversity in planktonic foraminifera but reveals unknown hyper-abundant lineages.

    PubMed

    Morard, Raphaël; Garet-Delmas, Marie-José; Mahé, Frédéric; Romac, Sarah; Poulain, Julie; Kucera, Michal; de Vargas, Colomban

    2018-02-07

    Since the advent of DNA metabarcoding surveys, the planktonic realm is considered a treasure trove of diversity, inhabited by a small number of abundant taxa, and a hugely diverse and taxonomically uncharacterized consortium of rare species. Here we assess if the apparent underestimation of plankton diversity applies universally. We target planktonic foraminifera, a group of protists whose known morphological diversity is limited, taxonomically resolved and linked to ribosomal DNA barcodes. We generated a pyrosequencing dataset of ~100,000 partial 18S rRNA foraminiferal sequences from 32 size fractioned photic-zone plankton samples collected at 8 stations in the Indian and Atlantic Oceans during the Tara Oceans expedition (2009-2012). We identified 69 genetic types belonging to 41 morphotaxa in our metabarcoding dataset. The diversity saturated at local and regional scale as well as in the three size fractions and the two depths sampled indicating that the diversity of foraminifera is modest and finite. The large majority of the newly discovered lineages occur in the small size fraction, neglected by classical taxonomy. These unknown lineages dominate the bulk [>0.8 µm] size fraction, implying that a considerable part of the planktonic foraminifera community biomass has its origin in unknown lineages.

  4. The Unknowns and Possible Implications of Mandatory Labeling.

    PubMed

    McFadden, Brandon R

    2017-01-01

    The National Bioengineered Food Disclosure Standard requires a mandatory label for genetically modified (GM) food. Currently, some aspects of the bill are unknown, including what constitutes a food to be considered GM. The costs associated with this legislation will depend on how actors in the food value chain respond. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. New species and previously unknown males of neotropical cleptobiotic stingless bees (Hymenoptera, Apidae, Lestrimelitta)

    USDA-ARS?s Scientific Manuscript database

    Three new species of cleptobiotic stingless bees of the genus Lestrimelitta Friese, L. opita sp. n. and L. huilensis sp. n. from Colombia and L. catira sp. n. from Venezuela, are described and figured. The males of the Central American species L. chamelensis, L. danuncia, and L. mourei are also desc...

  6. Viral Diseases in Zebrafish: What Is Known and Unknown

    PubMed Central

    Crim, Marcus J.; Riley, Lela K.

    2013-01-01

    Naturally occurring viral infections have the potential to introduce confounding variability that leads to invalid and misinterpreted data. Whereas the viral diseases of research rodents are well characterized and closely monitored, no naturally occurring viral infections have been characterized for the laboratory zebrafish (Danio rerio), an increasingly important biomedical research model. Despite the ignorance about naturally occurring zebrafish viruses, zebrafish models are rapidly expanding in areas of biomedical research where the confounding effects of unknown infectious agents present a serious concern. In addition, many zebrafish research colonies remain linked to the ornamental (pet) zebrafish trade, which can contribute to the introduction of new pathogens into research colonies, whereas mice used for research are purpose bred, with no introduction of new mice from the pet industry. Identification, characterization, and monitoring of naturally occurring viruses in zebrafish are crucial to the improvement of zebrafish health, the reduction of unwanted variability, and the continued development of the zebrafish as a model organism. This article addresses the importance of identifying and characterizing the viral diseases of zebrafish as the scope of zebrafish models expands into new research areas and also briefly addresses zebrafish susceptibility to experimental viral infection and the utility of the zebrafish as an infection and immunology model. PMID:23382345

  7. 43. Photographer unknown September 1967 VISITOR INFORMATION KIOSK, LOCATED NEAR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    43. Photographer unknown September 1967 VISITOR INFORMATION KIOSK, LOCATED NEAR THE POWDER MILL ROAD INTERCHANGE. (NPS/NCR (cn) 9995-C) - Baltimore-Washington Parkway, Greenbelt, Prince George's County, MD

  8. 27. photographer unknown 10 July 1938 SHIP LOCK DEDICATION CEREMONIES. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. photographer unknown 10 July 1938 SHIP LOCK DEDICATION CEREMONIES. - Bonneville Project, Navigation Lock No. 1, Oregon shore of Columbia River near first Powerhouse, Bonneville, Multnomah County, OR

  9. 61. photographer unknown undated FIRST CONCRETE BEING POURED IN DRAFT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    61. photographer unknown undated FIRST CONCRETE BEING POURED IN DRAFT TUBE FLOOR SLAB. - Bonneville Project, Powerhouse No.1, Spanning Bradford Slough, from Bradford Island, Bonneville, Multnomah County, OR

  10. Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.

    PubMed

    Fiz, Francesco; Marini, Cecilia; Campi, Cristina; Massone, Anna Maria; Podestà, Marina; Bottoni, Gianluca; Piva, Roberta; Bongioanni, Francesca; Bacigalupo, Andrea; Piana, Michele; Sambuceti, Gianmario; Frassoni, Francesco

    2015-06-25

    Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites. © 2015 by The American Society of Hematology.

  11. Investigating the effect of previous treatments on wheat biomass over multiple spatial frequencies

    NASA Astrophysics Data System (ADS)

    Milne, A. E.; Castellanos, M. T.; Cartagena, M. C.; Tarquis, A. M.; Lark, R. M.

    2010-09-01

    In this study we use the maximum overlap discrete packet transform (MODWPT) to investigate residual effects on wheat biomass of fertigation treatments applied to a previous crop. The wheat crop covered nine subplots from a previous experiment on melon response to fertigation. Each subplot had previously received a different level of applied nitrogen. Many factors affect wheat biomass, causing it to vary at different spatial frequencies. We hypothesize that these will include residual effects from fertilizer application (at relatively low spatial frequencies) and the local influence of individual plants from the previous melon crop (at high frequency). To test this hypothesis we use the MODWPT to identify the dominant spatial frequencies of wheat biomass variation, and analyse the relationship to both the previous fertilizer application and the location of individual melon plants in the previous crop. The MODWPT is particularly appropriate for this because it allows us first to identify the key spatial frequencies in the wheat biomass objectively and to analyse them, and their relationship to hypothesized driving factors without any assumptions of uniformity (stationarity) of wheat-biomass variation. The results showed that the applied nitrogen dominated the wheat biomass response, and that there was a noticeable component of wheat-biomass variation at the spatial frequency that corresponds to the melon cropping. We expected wheat biomass to be negatively correlated with the position of melons in the previous crop, due to uptake of the applied nitrogen. The MODWPT, which allows us to detect changes in correlation between variables at different frequencies, showed that such a relationship was found across part of the experiment but not uniformly.

  12. What bacteria are living in my food? An open-ended practical series involving identification of unknown foodborne bacteria using molecular techniques.

    PubMed

    Prasad, Prascilla; Turner, Mark S

    2011-01-01

    This open-ended practical series titled "Molecular Identification of Unknown Food Bacteria" which extended over a 6-week period was designed with the aims of giving students an opportunity to gain an understanding of naturally occurring food bacteria and skills in contemporary molecular methods using real food samples. The students first isolated two unknown bacterial strains from two food sources from which they extracted DNA and performed PCR targeting the 16S rRNA gene. Gel electrophoresis was used to analyze both genomic DNA preparations and PCR products. Following purification of PCR products, DNA sequencing was carried out and sequence trace quality was analyzed. The students successfully identified the two unknown bacteria using the BLAST search engine and a wide variety of different organisms were found. Assessment of their understanding of the procedure and ability to explain their findings using supporting primary research literature was via an individually prepared written report. Feedback from students over 2 years (n = 52) in a questionnaire revealed that the practical series was an engaging learning experience and lead to perceived improvements in knowledge of molecular techniques and bioinformatics and also about commonly occurring bacteria in foods. Copyright © 2011 Wiley Periodicals, Inc.

  13. 34. photographer unknown September 1937 ROOSEVELT ARRIVING FOR DEDICATION OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    34. photographer unknown September 1937 ROOSEVELT ARRIVING FOR DEDICATION OF BONNEVILLE DAM. - Bonneville Project, Columbia River, 1 mile Northeast of Exit 40, off Interstate 84, Bonneville, Multnomah County, OR

  14. 72. photographer unknown 22 November 1935 PLACING CONCRETE FORM FOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    72. photographer unknown 22 November 1935 PLACING CONCRETE FORM FOR STATION SERVICE DRAFT TUBES. - Bonneville Project, Powerhouse No.1, Spanning Bradford Slough, from Bradford Island, Bonneville, Multnomah County, OR

  15. Distributed Optimization Design of Continuous-Time Multiagent Systems With Unknown-Frequency Disturbances.

    PubMed

    Wang, Xinghu; Hong, Yiguang; Yi, Peng; Ji, Haibo; Kang, Yu

    2017-05-24

    In this paper, a distributed optimization problem is studied for continuous-time multiagent systems with unknown-frequency disturbances. A distributed gradient-based control is proposed for the agents to achieve the optimal consensus with estimating unknown frequencies and rejecting the bounded disturbance in the semi-global sense. Based on convex optimization analysis and adaptive internal model approach, the exact optimization solution can be obtained for the multiagent system disturbed by exogenous disturbances with uncertain parameters.

  16. Transcriptome Sequencing Reveals Wide Expression Reprogramming of Basal and Unknown Genes in Leptospira biflexa Biofilms

    PubMed Central

    Spangenberg, Lucía; Lopes Bastos, Bruno; Graña, Martín; Vasconcelos, Larissa; Almeida, Áurea; Greif, Gonzalo; Robello, Carlos; Ristow, Paula

    2016-01-01

    ABSTRACT The genus Leptospira is composed of pathogenic and saprophytic spirochetes. Pathogenic Leptospira is the etiological agent of leptospirosis, a globally spread neglected disease. A key ecological feature of some pathogenic species is their ability to survive both within and outside the host. For most leptospires, the ability to persist outside the host is associated with biofilm formation, a most important bacterial strategy to face and overcome hostile environmental conditions. The architecture and biochemistry of leptospiral biofilms are rather well understood; however, the genetic program underpinning biofilm formation remains mostly unknown. In this work, we used the saprophyte Leptospira biflexa as a model organism to assess over- and underrepresented transcripts during the biofilm state, using transcriptome sequencing (RNA-seq) technology. Our results showed that some basal biological processes like DNA replication and cell division are downregulated in the mature biofilm. Additionally, we identified significant expression reprogramming for genes involved in motility, sugar/lipid metabolism, and iron scavenging, as well as for outer membrane-encoding genes. A careful manual annotation process allowed us to assign molecular functions to many previously uncharacterized genes that are probably involved in biofilm metabolism. We also provided evidence for the presence of small regulatory RNAs in this species. Finally, coexpression networks were reconstructed to pinpoint functionally related gene clusters that may explain how biofilm maintenance is regulated. Beyond elucidating some genetic aspects of biofilm formation, this work reveals a number of pathways whose functional dissection may impact our understanding of leptospiral biology, in particular how these organisms adapt to environmental changes. IMPORTANCE In this work, we describe the first transcriptome based on RNA-seq technology focused on studying transcriptional changes associated with biofilm

  17. Transcriptome Sequencing Reveals Wide Expression Reprogramming of Basal and Unknown Genes in Leptospira biflexa Biofilms.

    PubMed

    Iraola, Gregorio; Spangenberg, Lucía; Lopes Bastos, Bruno; Graña, Martín; Vasconcelos, Larissa; Almeida, Áurea; Greif, Gonzalo; Robello, Carlos; Ristow, Paula; Naya, Hugo

    2016-01-01

    The genus Leptospira is composed of pathogenic and saprophytic spirochetes. Pathogenic Leptospira is the etiological agent of leptospirosis, a globally spread neglected disease. A key ecological feature of some pathogenic species is their ability to survive both within and outside the host. For most leptospires, the ability to persist outside the host is associated with biofilm formation, a most important bacterial strategy to face and overcome hostile environmental conditions. The architecture and biochemistry of leptospiral biofilms are rather well understood; however, the genetic program underpinning biofilm formation remains mostly unknown. In this work, we used the saprophyte Leptospira biflexa as a model organism to assess over- and underrepresented transcripts during the biofilm state, using transcriptome sequencing (RNA-seq) technology. Our results showed that some basal biological processes like DNA replication and cell division are downregulated in the mature biofilm. Additionally, we identified significant expression reprogramming for genes involved in motility, sugar/lipid metabolism, and iron scavenging, as well as for outer membrane-encoding genes. A careful manual annotation process allowed us to assign molecular functions to many previously uncharacterized genes that are probably involved in biofilm metabolism. We also provided evidence for the presence of small regulatory RNAs in this species. Finally, coexpression networks were reconstructed to pinpoint functionally related gene clusters that may explain how biofilm maintenance is regulated. Beyond elucidating some genetic aspects of biofilm formation, this work reveals a number of pathways whose functional dissection may impact our understanding of leptospiral biology, in particular how these organisms adapt to environmental changes. IMPORTANCE In this work, we describe the first transcriptome based on RNA-seq technology focused on studying transcriptional changes associated with biofilm growth

  18. 2. Photocopy of photograph (from Reading Co. Archives) Photographer unknown ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Photocopy of photograph (from Reading Co. Archives) Photographer unknown ca. 1937 NORTHEAST FRONT AND SOUTHEAST SIDE - Philadelphia & Reading Railroad, Terminal Station, 1115-1141 Market Street, Philadelphia, Philadelphia County, PA

  19. 62. photographer unknown undated ERECTING FORMS, PLACING REINFORCING STEEL, AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    62. photographer unknown undated ERECTING FORMS, PLACING REINFORCING STEEL, AND CONCRETING DRAFT PIER OF POWERHOUSE. - Bonneville Project, Powerhouse No.1, Spanning Bradford Slough, from Bradford Island, Bonneville, Multnomah County, OR

  20. 73. photographer unknown 9 January 1936 TOP OF DRAFT TUBE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    73. photographer unknown 9 January 1936 TOP OF DRAFT TUBE LINER AND SPEED RING PIERS. - Bonneville Project, Powerhouse No.1, Spanning Bradford Slough, from Bradford Island, Bonneville, Multnomah County, OR

  1. 60. photographer unknown undated CONCRETE BEING POURED ON CENTER PORTION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    60. photographer unknown undated CONCRETE BEING POURED ON CENTER PORTION OF DRAFT TUBE FLOOR SLAB. - Bonneville Project, Powerhouse No.1, Spanning Bradford Slough, from Bradford Island, Bonneville, Multnomah County, OR

  2. 80. photographer unknown 7 June 1937 PLACING MAIN THRUST BEARING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    80. photographer unknown 7 June 1937 PLACING MAIN THRUST BEARING ASSEMBLY IN UNIT NO 2. - Bonneville Project, Powerhouse No.1, Spanning Bradford Slough, from Bradford Island, Bonneville, Multnomah County, OR

  3. 6. FORSYTHIA WALK AFTER WIDENING Photocopy of photograph, date unknown ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. FORSYTHIA WALK AFTER WIDENING Photocopy of photograph, date unknown National Park Service, National Capital Region files - Dumbarton Oaks Park, Thirty-second & R Streets Northwest, Washington, District of Columbia, DC

  4. 22. Photographer unknown, 1956 AERIAL VIEW, LOOKING SOUTHSOUTHEAST, BUILDING 20 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Photographer unknown, 1956 AERIAL VIEW, LOOKING SOUTH-SOUTHEAST, BUILDING 20 AT LEFT. DARK AREAS ARE LANDSCAPED. - U. S. Veterans Administration Medical Center, 2100 Ridgecrest Southeast, Albuquerque, Bernalillo County, NM

  5. Gossypolhemiquinone, a dimeric sesquiterpenoid identified in cotton (Gossypium).

    PubMed

    Stipanovic, Robert; Puckhaber, Lorraine; Frelichowski, James; Esquivel, Jesus; Westbrook, John; O'Neil, Mike; Bell, Alois; Dowd, Michael; Hake, Kater; Duke, Sara

    2016-02-01

    The report that the cotton leaf perforator, Bucculatrix thurberiella, is one of the few insect herbivores to attack Gossypium thurberi prompted an investigation of the terpenoids present in the leaves of this wild species of cotton. Members of Gossypium produce subepidermal pigment glands in their leaves that contain the dimeric sesquiterpenoid gossypol as well as other biosynthetically related terpenoids. In addition to gossypol, a previously unknown dimeric sesquiterpenoid, gossypolhemiquinone (GHQ), was identified in trace amounts in G. thurberi, a member of the D genome. Other members of the D genome of Gossypium were subsequently found to contain this compound, but GHQ was not detected in commercial cotton cultivars. When fed to Helicoverpa zea in an artificial diet, GHQ delayed days-to-pupation, reduced pupal weights, and survival to adulthood to a lesser or equal extent than gossypol in comparison to the control diet. However, GHQ had a synergistic effect on survival and days-to-pupation when combined with gossypol at the highest dosage tested (0.18%; 15.5:84.5 GHQ:gossypol). Because gossypol exhibits anti-cancer activity, GHQ was also evaluated for its anti-cancer activity against the National Cancer Institute's 60-Human Tumor Cell Line Screen. Significant inhibitory activity against most of these cell lines was not observed, but the results may offer some promise against leukemia cancer cell lines. Published by Elsevier Ltd.

  6. Race Unknown

    ERIC Educational Resources Information Center

    Gray, Katti

    2011-01-01

    Bryan Lee, a senior at the University of California, Irvine, has noticed that some of his classmates adamantly declare their multiracial heritage while others choose not to identify themselves as being any particular ethnicity. The half-Korean, half-White biomedical engineering major is co-president of the university's Mixed Students Organization…

  7. Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins.

    PubMed

    Macaulay, Iain C; Tijssen, Marloes R; Thijssen-Timmer, Daphne C; Gusnanto, Arief; Steward, Michael; Burns, Philippa; Langford, Cordelia F; Ellis, Peter D; Dudbridge, Frank; Zwaginga, Jaap-Jan; Watkins, Nicholas A; van der Schoot, C Ellen; Ouwehand, Willem H

    2007-04-15

    To identify previously unknown platelet receptors we compared the transcriptomes of in vitro differentiated megakaryocytes (MKs) and erythroblasts (EBs). RNA was obtained from purified, biologically paired MK and EB cultures and compared using cDNA microarrays. Bioinformatical analysis of MK-up-regulated genes identified 151 transcripts encoding transmembrane domain-containing proteins. Although many of these were known platelet genes, a number of previously unidentified or poorly characterized transcripts were also detected. Many of these transcripts, including G6b, G6f, LRRC32, LAT2, and the G protein-coupled receptor SUCNR1, encode proteins with structural features or functions that suggest they may be involved in the modulation of platelet function. Immunoblotting on platelets confirmed the presence of the encoded proteins, and flow cytometric analysis confirmed the expression of G6b, G6f, and LRRC32 on the surface of platelets. Through comparative analysis of expression in platelets and other blood cells we demonstrated that G6b, G6f, and LRRC32 are restricted to the platelet lineage, whereas LAT2 and SUCNR1 were also detected in other blood cells. The identification of the succinate receptor SUCNR1 in platelets is of particular interest, because physiologically relevant concentrations of succinate were shown to potentiate the effect of low doses of a variety of platelet agonists.

  8. MXLKID: a maximum likelihood parameter identifier. [In LRLTRAN for CDC 7600

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

    Gavel, D.T.

    MXLKID (MaXimum LiKelihood IDentifier) is a computer program designed to identify unknown parameters in a nonlinear dynamic system. Using noisy measurement data from the system, the maximum likelihood identifier computes a likelihood function (LF). Identification of system parameters is accomplished by maximizing the LF with respect to the parameters. The main body of this report briefly summarizes the maximum likelihood technique and gives instructions and examples for running the MXLKID program. MXLKID is implemented LRLTRAN on the CDC7600 computer at LLNL. A detailed mathematical description of the algorithm is given in the appendices. 24 figures, 6 tables.

  9. An unbiased approach to identify genes involved in development in a turtle with temperature-dependent sex determination.

    PubMed

    Chojnowski, Jena L; Braun, Edward L

    2012-07-15

    Many reptiles exhibit temperature-dependent sex determination (TSD). The initial cue in TSD is incubation temperature, unlike genotypic sex determination (GSD) where it is determined by the presence of specific alleles (or genetic loci). We used patterns of gene expression to identify candidates for genes with a role in TSD and other developmental processes without making a priori assumptions about the identity of these genes (ortholog-based approach). We identified genes with sexually dimorphic mRNA accumulation during the temperature sensitive period of development in the Red-eared slider turtle (Trachemys scripta), a turtle with TSD. Genes with differential mRNA accumulation in response to estrogen (estradiol-17β; E(2)) exposure and developmental stages were also identified. Sequencing 767 clones from three suppression-subtractive hybridization libraries yielded a total of 581 unique sequences. Screening a macroarray with a subset of those sequences revealed a total of 26 genes that exhibited differential mRNA accumulation: 16 female biased and 10 male biased. Additional analyses revealed that C16ORF62 (an unknown gene) and MALAT1 (a long noncoding RNA) exhibited increased mRNA accumulation at the male producing temperature relative to the female producing temperature during embryonic sexual development. Finally, we identified four genes (C16ORF62, CCT3, MMP2, and NFIB) that exhibited a stage effect and five genes (C16ORF62, CCT3, MMP2, NFIB and NOTCH2) showed a response to E(2) exposure. Here we report a survey of genes identified using patterns of mRNA accumulation during embryonic development in a turtle with TSD. Many previous studies have focused on examining the turtle orthologs of genes involved in mammalian development. Although valuable, the limitations of this approach are exemplified by our identification of two genes (MALAT1 and C16ORF62) that are sexually dimorphic during embryonic development. MALAT1 is a noncoding RNA that has not been implicated

  10. 38. Historic photograph, photographer unknown, c. 1944. VIEW SHOWING BURROS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. Historic photograph, photographer unknown, c. 1944. VIEW SHOWING BURROS (OR MULES) CROSSING BRIDGE, LOOKING NORTHEAST. - Verde River Sheep Bridge, Spanning Verde River (Tonto National Forest), Cave Creek, Maricopa County, AZ

  11. 81. photographer unknown 11 June 1937 WORKMEN ON TURBINE BLADES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    81. photographer unknown 11 June 1937 WORKMEN ON TURBINE BLADES BEFORE LOWERING INTO DRAFT TUBE LINER. - Bonneville Project, Powerhouse No.1, Spanning Bradford Slough, from Bradford Island, Bonneville, Multnomah County, OR

  12. 4. VIEW OF BORING MILL IN OPERATION, operator unknown (note ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. VIEW OF BORING MILL IN OPERATION, operator unknown (note console in background). - Juniata Shops, Erecting Shop & Machine Shop, East of Fourth Avenue, between Fourth & Fifth Streets, Altoona, Blair County, PA

  13. 3. VIEW OF BORING MILL IN OPERATION, operator unknown (note ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. VIEW OF BORING MILL IN OPERATION, operator unknown (note console in background). - Juniata Shops, Erecting Shop & Machine Shop, East of Fourth Avenue, between Fourth & Fifth Streets, Altoona, Blair County, PA

  14. 7. Photographic copy of photograph (date unknown, original print in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Photographic copy of photograph (date unknown, original print in the possession of the Wisconsin Veterans Museums). LAKE IN FOREGROUND, COTTAGES IN BACK. - Wisconsin Home for Veterans, King, Waupaca County, WI

  15. Ability of the medical priority dispatch system protocol to predict the acuity of "unknown problem" dispatch response levels.

    PubMed

    Clawson, Jeff; Olola, Christopher; Heward, Andy; Patterson, Brett; Scott, Greg

    2008-01-01

    dispatcher (EMD) reliance on caller-volunteered information to identify predefined critical situations does not appear to add to the protocol's ability to differentiate high-acuity and CA patients. LSQ proved to be a better predictor of both CA and BI outcomes, when compared with the BRAVO-level determinant codes within the "unknown problem" chief complaint. The B-3 (completely unknown) determinant code is a better predictor of severe outcomes than nearly all of the clinically similar BRAVO determinant codes in the entire MPDS protocol. Hence, the B-3 coding should be considered-in terms of its predictability for severe outcome-as falling somewhere between a typical DELTA and a typical BRAVO determinant code.

  16. Screening for autism identifies behavioral disorders in children functional defecation disorders.

    PubMed

    Kuizenga-Wessel, Sophie; Di Lorenzo, Carlo; Nicholson, Lisa M; Butter, Eric M; Ratliff-Schaub, Karen L; Benninga, Marc A; Williams, Kent C

    2016-10-01

    This study prospectively assessed whether positive screening surveys for autism spectrum disorders (ASDs) in children with functional defecation disorders (FDDs) accurately identify ASD. Parents of children (4-12 years) who met Rome III criteria for functional constipation (FC), FC with fecal incontinence (FI) and functional nonretentive FI (FNRFI) completed two ASD screening surveys. Children with positive screens were referred for psychological evaluation, and a year later, follow-up surveys were conducted. Of the 97 study participants, 30.9 % were diagnosed with FC, 62.9 % with FC with FI, and 6.2 % with FNRFI. ASD surveys were positive for 27 children (27.8 %). New DSM diagnoses were made in 10 out of the 15 children that completed further evaluation. Two (2.1 %) met criteria for ASD, and 12 (12.4 %) met criteria for other behavioral disorders. Average SRS and SCQ-L scores were higher in subjects with FC with FI as compared to FC alone and in those who reported no improvement versus those who reported improvement 1 year later. While positive ASD screening surveys did not correctly identify ASD in the majority, it did help to identify other unrecognized behavioral disorders in children with FDD. High screening scores were more common in children with FC with FI and in children with poorer responses to current medical treatments. •A prior study found that 29 % of children with FDD scored positive on ASD screening questionnaires. •Whether positive screens correctly identify ASD in children with FDD is unknown. What is New: •This study shows that positive ASD screens do not correctly identify ASD in children with FDD. However, the use of ASD screening questionnaires can identify previously unrecognized and untreated behavioral/developmental disorders in children with FDD. •High screening scores are more common in children with FC with FI and in children with poorer responses to current medical treatments.

  17. Identifiability of Additive Actuator and Sensor Faults by State Augmentation

    NASA Technical Reports Server (NTRS)

    Joshi, Suresh; Gonzalez, Oscar R.; Upchurch, Jason M.

    2014-01-01

    A class of fault detection and identification (FDI) methods for bias-type actuator and sensor faults is explored in detail from the point of view of fault identifiability. The methods use state augmentation along with banks of Kalman-Bucy filters for fault detection, fault pattern determination, and fault value estimation. A complete characterization of conditions for identifiability of bias-type actuator faults, sensor faults, and simultaneous actuator and sensor faults is presented. It is shown that FDI of simultaneous actuator and sensor faults is not possible using these methods when all sensors have unknown biases. The fault identifiability conditions are demonstrated via numerical examples. The analytical and numerical results indicate that caution must be exercised to ensure fault identifiability for different fault patterns when using such methods.

  18. Previous history of tuberculosis is associated with rheumatoid arthritis.

    PubMed

    Shen, T-C; Lin, C-L; Wei, C-C; Chen, C-H; Tu, C-Y; Hsia, T-C; Shih, C-M; Hsu, W-H; Chung, C-J; Sung, F-C; Kao, C-H

    2015-11-01

    Previous studies have suggested that mycobacterial infections could trigger autoimmune diseases, including rheumatoid arthritis (RA). To explore the association between previous tuberculosis (TB) and RA. We conducted a case-control study using data obtained from the National Health Insurance (NHI) system of Taiwan. We identified 26 535 adults with RA from 2002 to 2011, with the date of diagnosis as the index date. This number was randomly selected and frequency-matched four times by age, sex and the year of index date from among non-RA individuals. Odds ratios (ORs) of RA were calculated for associations with TB. Compared with controls, RA patients had a crude OR of 1.77 for TB (95%CI 1.61-1.94). The strength of the association between RA and TB remained at the same level after controlling for other potential risk factors (adjusted OR 1.73, 95%CI 1.57-1.90), although RA patients tended to have a higher prevalence of hypertension, coronary artery disease and kidney disease. TB was much more prevalent in RA patients than in control subjects. Prospective cohort studies are required to establish a causal relationship between previous TB and RA.

  19. Quadrotor Control in the Presence of Unknown Mass Properties

    NASA Astrophysics Data System (ADS)

    Duivenvoorden, Rikky Ricardo Petrus Rufino

    Quadrotor UAVs are popular due to their mechanical simplicity, as well as their capability to hover and vertically take-off and land. As applications diversify, quadrotors are increasingly required to operate under unknown mass properties, for example as a multirole sensor platform or for package delivery operations. The work presented here consists of the derivation of a generalized quadrotor dynamic model without the typical simplifying assumptions on the first and second moments of mass. The maximum payload capacity of a quadrotor in hover, and the observability of the unknown mass properties are discussed. A brief introduction of L1 adaptive control is provided, and three different L 1 adaptive controllers were designed for the Parrot AR.Drone quadrotor. Their tracking and disturbance rejection performance was compared to the baseline nonlinear controller in experiments. Finally, the results of the combination of L1 adaptive control with iterative learning control are presented, showing high performance trajectory tracking under uncertainty.

  20. 19. Photocopy of photograph Photographer unknown, ca. 1895 GENERAL VIEW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Photocopy of photograph Photographer unknown, ca. 1895 GENERAL VIEW OF KEY WEST WITH FORT TAYLOR IN THE BACKGROUND LOOKING WEST SOUTHWEST - Fort Taylor, Whitehead Spit Vicinity, Key West, Monroe County, FL

  1. 15. Photocopy of photograph (original in WACC), photographer unknown, c. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Photocopy of photograph (original in WACC), photographer unknown, c. 1917 BEN ERICKSON IN WWI UNIFORM STANDING IN FRONT OF SOUTH LIVING ROOM WINDOW (ADOBE WALLS) - Faraway Ranch, Willcox, Cochise County, AZ

  2. 71. photographer unknown 9 September 1935 DOWNSTREAM SIDE OF POWERHOUSE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    71. photographer unknown 9 September 1935 DOWNSTREAM SIDE OF POWERHOUSE SUBSTRUCTURE, SHOWING FISHWAY AND DRAFT TUBE OUTLETS. - Bonneville Project, Powerhouse No.1, Spanning Bradford Slough, from Bradford Island, Bonneville, Multnomah County, OR

  3. 41. Upstream end of emergency spillway excavation. Photographer unknown, 1929. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. Upstream end of emergency spillway excavation. Photographer unknown, 1929. Source: Arizona Department of Water Resources (ADWR). - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  4. 35. Photocopy of drawing (from Library of Congress) Artist unknown ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    35. Photocopy of drawing (from Library of Congress) Artist unknown 1891 SOUTH FRONT FROM THE SOUTHWEST - Patent Office Building, Bounded by Seventh, Ninth, F & G Streets, Northwest, Washington, District of Columbia, DC

  5. 3. Photocopy of photograph (location of original unknown) Mary Mather, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Photocopy of photograph (location of original unknown) Mary Mather, photographer, ca. 1920 PARTIAL EAST ELEVATION, OBSCURED BY FOLIAGE - Bagatelle Plantation, East River Road (moved to Iberville Parish), Donaldsonville, Ascension Parish, LA

  6. 51. BOILER ROOM. SMALL BOILER ON LEFT OF UNKNOWN MANUFACTURE, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    51. BOILER ROOM. SMALL BOILER ON LEFT OF UNKNOWN MANUFACTURE, WITH INDUCTION MOTORS. HARTLEY BOILER, MONTGOMERY, ALABAMA, ON RIGHT. - Prattville Manufacturing Company, Number One, 242 South Court Street, Prattville, Autauga County, AL

  7. Matrix- and tensor-based recommender systems for the discovery of currently unknown inorganic compounds

    NASA Astrophysics Data System (ADS)

    Seko, Atsuto; Hayashi, Hiroyuki; Kashima, Hisashi; Tanaka, Isao

    2018-01-01

    Chemically relevant compositions (CRCs) and atomic arrangements of inorganic compounds have been collected as inorganic crystal structure databases. Machine learning is a unique approach to search for currently unknown CRCs from vast candidates. Herein we propose matrix- and tensor-based recommender system approaches to predict currently unknown CRCs from database entries of CRCs. Firstly, the performance of the recommender system approaches to discover currently unknown CRCs is examined. A Tucker decomposition recommender system shows the best discovery rate of CRCs as the majority of the top 100 recommended ternary and quaternary compositions correspond to CRCs. Secondly, systematic density functional theory (DFT) calculations are performed to investigate the phase stability of the recommended compositions. The phase stability of the 27 compositions reveals that 23 currently unknown compounds are newly found to be stable. These results indicate that the recommender system has great potential to accelerate the discovery of new compounds.

  8. High dose intensity of cisplatin and etoposide in adenocarcinoma of unknown primary.

    PubMed

    Gill, I; Guaglianone, P; Grunberg, S M; Scholz, M; Muggia, F M

    1991-01-01

    Adenocarcinoma of unknown primary (AUP) has generally a poor prognosis. Previous studies have suggested that Cisplatin and Etoposide have activity in AUP. The aim of this study was to determine if dose intensification of this combination would result in increased efficacy. Each 28 day cycle consisted of Cisplatin 100 mg/m2 given on Day 1 and 8 with Etoposide 80 mg/m2 given on day 1, 2, 8 and 9. Sixteen patients (Pts) with no prior chemotherapy were accrued to this study. Predominant sites of disease were lung, liver, and bone. BHCG and AFP were not elevated. One complete remission was seen in a patient with a mediastinal mass (duration of remission = 59 weeks). Two other patients had a partial response. Overall response rate was 19%. Moderate to severe renal toxicity was recorded in 8 patients, with neuro- and ototoxicities in 2 patients each. Severe granulocytopenia occurred in 8 patients, and one patient died of congestive heart failure on day 1 of cycle 2. This excessive toxicity, without enhanced efficacy does not encourage a more extensive empiric trial by this dose schedule in the treatment of AUP.

  9. Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma.

    PubMed

    Chahal, Harvind S; Lin, Yuan; Ransohoff, Katherine J; Hinds, David A; Wu, Wenting; Dai, Hong-Ji; Qureshi, Abrar A; Li, Wen-Qing; Kraft, Peter; Tang, Jean Y; Han, Jiali; Sarin, Kavita Y

    2016-07-18

    Cutaneous squamous cell carcinoma represents the second most common cutaneous malignancy, affecting 7-11% of Caucasians in the United States. The genetic determinants of susceptibility to cutaneous squamous cell carcinoma remain largely unknown. Here we report the results of a two-stage genome-wide association study of cutaneous squamous cell carcinoma, totalling 7,404 cases and 292,076 controls. Eleven loci reached genome-wide significance (P<5 × 10(-8)) including seven previously confirmed pigmentation-related loci: MC1R, ASIP, TYR, SLC45A2, OCA2, IRF4 and BNC2. We identify an additional four susceptibility loci: 11q23.3 CADM1, a metastasis suppressor gene involved in modifying tumour interaction with cell-mediated immunity; 2p22.3; 7p21.1 AHR, the dioxin receptor involved in anti-apoptotic pathways and melanoma progression; and 9q34.3 SEC16A, a putative oncogene with roles in secretion and cellular proliferation. These susceptibility loci provide deeper insight into the pathogenesis of squamous cell carcinoma.

  10. 47. Photocopy of postcard (Pentran file), photographer unknown. Hampton's Old ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    47. Photocopy of postcard (Pentran file), photographer unknown. Hampton's Old Point Comfort electric trolley in 1921. - Newport News & Old Point Railway & Electric Company, Trolley Barn & Administration Building, 3400 Victoria Boulevard, Hampton, Hampton, VA

  11. LAPAROSCOPY AFTER PREVIOUS LAPAROTOMY

    PubMed Central

    Godinjak, Zulfo; Idrizbegović, Edin; Begić, Kerim

    2006-01-01

    Following the abdominal surgery, extensive adhesions often occur and they can cause difficulties during laparoscopic operations. However, previous laparotomy is not considered to be a contraindication for lap-aroscopy. The aim of this study is to present that an insertion of Veres needle in the region of umbilicus is a safe method for creating a pneumoperitoneum for laparoscopic operations after previous laparotomy. In the last three years, we have performed 144 laparoscopic operations in patients that previously underwent one or two laparotomies. Pathology of digestive system, genital organs, Cesarean Section or abdominal war injuries were the most common causes of previous laparotomy. During those operations or during entering into abdominal cavity we have not experienced any complications, while in 7 patients we performed conversion to laparotomy following the diagnostic laparoscopy. In all patients an insertion of Veres needle and trocar insertion in the umbilical region was performed, namely a technique of closed laparoscopy. Not even in one patient adhesions in the region of umbilicus were found, and no abdominal organs were injured. PMID:17177649

  12. Identifiability Results for Several Classes of Linear Compartment Models.

    PubMed

    Meshkat, Nicolette; Sullivant, Seth; Eisenberg, Marisa

    2015-08-01

    Identifiability concerns finding which unknown parameters of a model can be estimated, uniquely or otherwise, from given input-output data. If some subset of the parameters of a model cannot be determined given input-output data, then we say the model is unidentifiable. In this work, we study linear compartment models, which are a class of biological models commonly used in pharmacokinetics, physiology, and ecology. In past work, we used commutative algebra and graph theory to identify a class of linear compartment models that we call identifiable cycle models, which are unidentifiable but have the simplest possible identifiable functions (so-called monomial cycles). Here we show how to modify identifiable cycle models by adding inputs, adding outputs, or removing leaks, in such a way that we obtain an identifiable model. We also prove a constructive result on how to combine identifiable models, each corresponding to strongly connected graphs, into a larger identifiable model. We apply these theoretical results to several real-world biological models from physiology, cell biology, and ecology.

  13. 44. Reinforcement construction to Pleasant Dam. Photographer unknown, 1935. Source: ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    44. Reinforcement construction to Pleasant Dam. Photographer unknown, 1935. Source: Huber Collection, University of California, Berkeley, Water Resources Library. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  14. 47. Photocopy of plans. Draftsman unknown, 1916 ADDITION TO CAR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    47. Photocopy of plans. Draftsman unknown, 1916 ADDITION TO CAR BARN. LONGITUDINAL AND CROSS SECTIONS. VIEWS TO SOUTH AND WEST. - Milwaukee Light, Heat & Traction Company, 8336 West Lapham Street, West Allis, Milwaukee County, WI

  15. Robot-assisted laparoscopic prostatectomy and previous surgical history: a multidisciplinary approach.

    PubMed

    Bernstein, Adrien N; Lavery, Hugh J; Hobbs, Adele R; Chin, Edward; Samadi, David B

    2013-06-01

    Previous abdominal or prostate surgery can be a significant barrier to subsequent minimally invasive procedures, including radical prostatectomy (RP). This is relevant to a quarter of prostatectomy patients who have had previous surgery. The technological advances of robot-assisted laparoscopic RP (RALP) can mitigate some of these challenges. To that end, our objective was to elucidate the effect of previous surgery on RALP, and to describe a multidisciplinary approach to the previously entered abdomen. One-thousand four-hundred and fourteen RALP patients were identified from a single-surgeon database. Potentially difficult cases were discussed preoperatively and treated in a multidisciplinary fashion with a general surgeon. Operative, pathological, and functional outcomes were analyzed after stratification by previous surgical history. Four-hundred and twenty (30 %) patients underwent previous surgery at least once. Perioperative outcomes were similar among most groups. Previous major abdominal surgery was associated with increased operative time (147 vs. 119 min, p < 0.001), as was the presence of adhesions (120 vs. 154 min, p < 0.001). Incidence of complications was comparable, irrespective of surgical history. Major complications included two enterotomies diagnosed intraoperatively and one patient requiring reoperation. All cases were performed robotically, without conversion to open-RP. There was no difference in biochemical disease-free survival among surgical groups and continence and potency were equivalent between groups. In conclusion, previous abdominal surgery did not affect the safety or feasibility of RALP, with all patients experiencing comparable perioperative, functional, and oncologic outcomes.

  16. A multiwave range test for obstacle reconstructions with unknown physical properties

    NASA Astrophysics Data System (ADS)

    Potthast, Roland; Schulz, Jochen

    2007-08-01

    We develop a new multiwave version of the range test for shape reconstruction in inverse scattering theory. The range test [R. Potthast, et al., A `range test' for determining scatterers with unknown physical properties, Inverse Problems 19(3) (2003) 533-547] has originally been proposed to obtain knowledge about an unknown scatterer when the far field pattern for only one plane wave is given. Here, we extend the method to the case of multiple waves and show that the full shape of the unknown scatterer can be reconstructed. We further will clarify the relation between the range test methods, the potential method [A. Kirsch, R. Kress, On an integral equation of the first kind in inverse acoustic scattering, in: Inverse Problems (Oberwolfach, 1986), Internationale Schriftenreihe zur Numerischen Mathematik, vol. 77, Birkhauser, Basel, 1986, pp. 93-102] and the singular sources method [R. Potthast, Point sources and multipoles in inverse scattering theory, Habilitation Thesis, Gottingen, 1999]. In particular, we propose a new version of the Kirsch-Kress method using the range test and a new approach to the singular sources method based on the range test and potential method. Numerical examples of reconstructions for all four methods are provided.

  17. A novel algorithm for fast grasping of unknown objects using C-shape configuration

    NASA Astrophysics Data System (ADS)

    Lei, Qujiang; Chen, Guangming; Meijer, Jonathan; Wisse, Martijn

    2018-02-01

    Increasing grasping efficiency is very important for the robots to grasp unknown objects especially subjected to unfamiliar environments. To achieve this, a new algorithm is proposed based on the C-shape configuration. Specifically, the geometric model of the used under-actuated gripper is approximated as a C-shape. To obtain an appropriate graspable position, this C-shape configuration is applied to fit geometric model of an unknown object. The geometric model of unknown object is constructed by using a single-view partial point cloud. To examine the algorithm using simulations, a comparison of the commonly used motion planners is made. The motion planner with the highest number of solved runs, lowest computing time and the shortest path length is chosen to execute grasps found by this grasping algorithm. The simulation results demonstrate that excellent grasping efficiency is achieved by adopting our algorithm. To validate this algorithm, experiment tests are carried out using a UR5 robot arm and an under-actuated gripper. The experimental results show that steady grasping actions are obtained. Hence, this research provides a novel algorithm for fast grasping of unknown objects.

  18. The Unicorn Cave, Southern Harz Mountains, Germany: From known passages to unknown extensions with the help of geophysical surveys

    NASA Astrophysics Data System (ADS)

    Kaufmann, Georg; Nielbock, Ralf; Romanov, Douchko

    2015-12-01

    In soluble rocks (limestone, dolomite, anhydrite, gypsum, …), fissures and bedding partings can be enlarged with time by both physical and chemical dissolution of the host rock. With time, larger cavities evolve, and a network of cave passages can evolve. If the enlarged cave voids are not too deep under the surface, geophysical measurements can be used to detect, identify and trace these karst structures, e.g.: (i) gravity revealing air- and sediment-filled cave voids through negative Bouguer anomalies, (ii) electrical resistivity imaging (ERI) mapping different infillings of cavities either as high resistivities from air-filled voids or dry soft sediments, or low resistivities from saturated sediments, and (iii) groundwater flow through electrical potential differences (SP) arising from dislocated ionic charges from the walls of the underground flow paths. We have used gravity, ERI, and SP methods both in and above the Unicorn Cave located in the southern Harz Mountains in Germany. The Unicorn Cave is a show cave developed in the Werra dolomite formation of the Permian Zechstein sequence, characterised by large trunk passages interrupted by larger rooms. The overburden of the cave is only around 15 m, and passages are filled with sediments reaching infill thicknesses up to 40 m. We present results from our geophysical surveys above the known cave and its northern and southern extension, and from the cave interior. We identify the cave geometry and its infill from gravity and ERI measurements, predict previously unknown parts of the cave, and subsequently confirm the existence of these new passages through drilling. From the wealth of geophysical data acquired we derive a three-dimensional structural model of the Unicorn Cave and its surrounding, especially the cave infill.

  19. Using whole-exome sequencing to investigate the genetic bases of lysosomal storage diseases of unknown etiology.

    PubMed

    Wang, Nan; Zhang, Yeting; Gedvilaite, Erika; Loh, Jui Wan; Lin, Timothy; Liu, Xiuping; Liu, Chang-Gong; Kumar, Dibyendu; Donnelly, Robert; Raymond, Kimiyo; Schuchman, Edward H; Sleat, David E; Lobel, Peter; Xing, Jinchuan

    2017-11-01

    Lysosomes are membrane-bound, acidic eukaryotic cellular organelles that play important roles in the degradation of macromolecules. Mutations that cause the loss of lysosomal protein function can lead to a group of disorders categorized as the lysosomal storage diseases (LSDs). Suspicion of LSD is frequently based on clinical and pathologic findings, but in some cases, the underlying genetic and biochemical defects remain unknown. Here, we performed whole-exome sequencing (WES) on 14 suspected LSD cases to evaluate the feasibility of using WES for identifying causal mutations. By examining 2,157 candidate genes potentially associated with lysosomal function, we identified eight variants in five genes as candidate disease-causing variants in four individuals. These included both known and novel mutations. Variants were corroborated by targeted sequencing and, when possible, functional assays. In addition, we identified nonsense mutations in two individuals in genes that are not known to have lysosomal function. However, mutations in these genes could have resulted in phenotypes that were diagnosed as LSDs. This study demonstrates that WES can be used to identify causal mutations in suspected LSD cases. We also demonstrate cases where a confounding clinical phenotype may potentially reflect more than one lysosomal protein defect. © 2017 Wiley Periodicals, Inc.

  20. 25. Photocopy of photograph (Source unknown, c. 19231925) EXTERIOR, CLOSEUP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. Photocopy of photograph (Source unknown, c. 1923-1925) EXTERIOR, CLOSE-UP OF SOUTH FRONT OF MISSION AFTER RESTORATION, C. 1923-1925 - Mission San Francisco Solano de Sonoma, First & Spain Streets, Sonoma, Sonoma County, CA

  1. 43. Photocopy of photograph (Pentran file), photographer and date unknown ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    43. Photocopy of photograph (Pentran file), photographer and date unknown (circa 1960). VIEW WEST, EAST SIDE ADMINISTRATION BUILDING - Newport News & Old Point Railway & Electric Company, Trolley Barn & Administration Building, 3400 Victoria Boulevard, Hampton, Hampton, VA

  2. View of an unknown industrial building in the Dolphin Jute ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of an unknown industrial building in the Dolphin Jute Mill Complex, looking southwest. Note Garret Mountain at upper left and historic Dexter-Lambert smokestack. - Dolphin Manufacturing Company, Spruce & Barbour Streets, Paterson, Passaic County, NJ

  3. Unknown Gases: Student-Designed Experiments in the Introductory Laboratory.

    ERIC Educational Resources Information Center

    Hanson, John; Hoyt, Tim

    2002-01-01

    Introductory students design and carry-out experimental procedures to determine the identity of three unknown gases from a list of eight possibilities: air, nitrogen, oxygen, argon, carbon dioxide, helium, methane, and hydrogen. Students are excited and motivated by the opportunity to come up with their own experimental approach to solving a…

  4. Active learning for ontological event extraction incorporating named entity recognition and unknown word handling.

    PubMed

    Han, Xu; Kim, Jung-jae; Kwoh, Chee Keong

    2016-01-01

    Biomedical text mining may target various kinds of valuable information embedded in the literature, but a critical obstacle to the extension of the mining targets is the cost of manual construction of labeled data, which are required for state-of-the-art supervised learning systems. Active learning is to choose the most informative documents for the supervised learning in order to reduce the amount of required manual annotations. Previous works of active learning, however, focused on the tasks of entity recognition and protein-protein interactions, but not on event extraction tasks for multiple event types. They also did not consider the evidence of event participants, which might be a clue for the presence of events in unlabeled documents. Moreover, the confidence scores of events produced by event extraction systems are not reliable for ranking documents in terms of informativity for supervised learning. We here propose a novel committee-based active learning method that supports multi-event extraction tasks and employs a new statistical method for informativity estimation instead of using the confidence scores from event extraction systems. Our method is based on a committee of two systems as follows: We first employ an event extraction system to filter potential false negatives among unlabeled documents, from which the system does not extract any event. We then develop a statistical method to rank the potential false negatives of unlabeled documents 1) by using a language model that measures the probabilities of the expression of multiple events in documents and 2) by using a named entity recognition system that locates the named entities that can be event arguments (e.g. proteins). The proposed method further deals with unknown words in test data by using word similarity measures. We also apply our active learning method for the task of named entity recognition. We evaluate the proposed method against the BioNLP Shared Tasks datasets, and show that our method

  5. Spread-Spectrum Carrier Estimation With Unknown Doppler Shift

    NASA Technical Reports Server (NTRS)

    DeLeon, Phillip L.; Scaife, Bradley J.

    1998-01-01

    We present a method for the frequency estimation of a BPSK modulated, spread-spectrum carrier with unknown Doppler shift. The approach relies on a classic periodogram in conjunction with a spectral matched filter. Simulation results indicate accurate carrier estimation with processing gains near 40. A DSP-based prototype has been implemented for real-time carrier estimation for use in New Mexico State University's proposal for NASA's Demand Assignment Multiple Access service.

  6. Persistent Surveillance of Transient Events with Unknown Statistics

    DTIC Science & Technology

    2016-12-18

    different bird species by a documentary maker is shown in Fig. 1. Additional examples of scenarios following this setting include robots patrolling the...persistent monitoring application in which a documentary maker would like to monitor three different species of birds appearing in three discrete, species...specific locations. Bird sightings at each location follow a stochastic process with a rate that is initially unknown to the documentary maker and must

  7. Characterization of previously unidentified lunar pyroclastic deposits using Lunar Reconnaissance Orbiter Camera (LROC) data

    USGS Publications Warehouse

    Gustafson, J. Olaf; Bell, James F.; Gaddis, Lisa R.R.; Hawke, B. Ray Ray; Giguere, Thomas A.

    2012-01-01

    We used a Lunar Reconnaissance Orbiter Camera (LROC) global monochrome Wide-angle Camera (WAC) mosaic to conduct a survey of the Moon to search for previously unidentified pyroclastic deposits. Promising locations were examined in detail using LROC multispectral WAC mosaics, high-resolution LROC Narrow Angle Camera (NAC) images, and Clementine multispectral (ultraviolet-visible or UVVIS) data. Out of 47 potential deposits chosen for closer examination, 12 were selected as probable newly identified pyroclastic deposits. Potential pyroclastic deposits were generally found in settings similar to previously identified deposits, including areas within or near mare deposits adjacent to highlands, within floor-fractured craters, and along fissures in mare deposits. However, a significant new finding is the discovery of localized pyroclastic deposits within floor-fractured craters Anderson E and F on the lunar farside, isolated from other known similar deposits. Our search confirms that most major regional and localized low-albedo pyroclastic deposits have been identified on the Moon down to ~100 m/pix resolution, and that additional newly identified deposits are likely to be either isolated small deposits or additional portions of discontinuous, patchy deposits.

  8. Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. The GRI Study Group.

    PubMed

    Bellaïche, L; Laredo, J D; Lioté, F; Koeger, A C; Hamze, B; Ziza, J M; Pertuiset, E; Bardin, T; Tubiana, J M

    1997-11-01

    A prospective multicenter study. To evaluate the use of magnetic resonance imaging, in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. Although multiple myeloma has been studied extensively with magnetic resonance imaging, to the authors' knowledge, no study has evaluated the clinical interest of magnetic resonance imaging in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. The magnetic resonance examinations of the thoracolumbar spine in 24 patients with newly diagnosed monoclonal gammopathies of unknown significance were compared with those performed in 44 patients with newly diagnosed nontreated multiple myeloma. All findings on magnetic resonance examination performed in patients with monoclonal gammopathies of unknown significance were normal, whereas findings on 38 (86%) of the 44 magnetic resonance examinations performed in patients with multiple myeloma were abnormal. Magnetic resonance imaging can be considered as an additional diagnostic tool in differentiating between monoclonal gammopathies of unknown significance and multiple myeloma, which may be helpful when routine criteria are not sufficient. An abnormal finding on magnetic resonance examination in a patient with monoclonal gammopathies of unknown significance should suggest the diagnosis of multiple myeloma after other causes of marrow signal abnormalities are excluded. Magnetic resonance imaging also may be proposed in the long-term follow-up of monoclonal gammopathies of unknown significance when a new biologic or clinical event suggests the diagnosis of malignant monoclonal gammopathy.

  9. 43. Photocopy of photograph, photographer unknown, ca January 1929 (original ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    43. Photocopy of photograph, photographer unknown, ca January 1929 (original print located at Arizona Department of Transportation, Phoenix AZ). COMPLETED BRIDGE. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  10. 356. Delineator Unknown March 1946 STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    356. Delineator Unknown March 1946 STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; GENERAL DATA; PLAT III - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  11. 6. Photographic copy of photograph (date unknown, original print in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photographic copy of photograph (date unknown, original print in the possession of the Wisconsin Veterans Museums). COTTAGES, INCLUDING 'J.P. McPHERSON POST NO. 27 CAFE GENEVA'. - Wisconsin Home for Veterans, King, Waupaca County, WI

  12. A Next-Generation Sequencing Data Analysis Pipeline for Detecting Unknown Pathogens from Mixed Clinical Samples and Revealing Their Genetic Diversity.

    PubMed

    Gong, Yu-Nong; Chen, Guang-Wu; Yang, Shu-Li; Lee, Ching-Ju; Shih, Shin-Ru; Tsao, Kuo-Chien

    2016-01-01

    Forty-two cytopathic effect (CPE)-positive isolates were collected from 2008 to 2012. All isolates could not be identified for known viral pathogens by routine diagnostic assays. They were pooled into 8 groups of 5-6 isolates to reduce the sequencing cost. Next-generation sequencing (NGS) was conducted for each group of mixed samples, and the proposed data analysis pipeline was used to identify viral pathogens in these mixed samples. Polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA) was individually conducted for each of these 42 isolates depending on the predicted viral types in each group. Two isolates remained unknown after these tests. Moreover, iteration mapping was implemented for each of these 2 isolates, and predicted human parechovirus (HPeV) in both. In summary, our NGS pipeline detected the following viruses among the 42 isolates: 29 human rhinoviruses (HRVs), 10 HPeVs, 1 human adenovirus (HAdV), 1 echovirus and 1 rotavirus. We then focused on the 10 identified Taiwanese HPeVs because of their reported clinical significance over HRVs. Their genomes were assembled and their genetic diversity was explored. One novel 6-bp deletion was found in one HPeV-1 virus. In terms of nucleotide heterogeneity, 64 genetic variants were detected from these HPeVs using the mapped NGS reads. Most importantly, a recombination event was found between our HPeV-3 and a known HPeV-4 strain in the database. Similar event was detected in the other HPeV-3 strains in the same clade of the phylogenetic tree. These findings demonstrated that the proposed NGS data analysis pipeline identified unknown viruses from the mixed clinical samples, revealed their genetic identity and variants, and characterized their genetic features in terms of viral evolution.

  13. Relationships between Causes of Fever of Unknown Origin and Inflammatory Markers: A Multicenter Collaborative Retrospective Study.

    PubMed

    Naito, Toshio; Torikai, Keito; Mizooka, Masafumi; Mitsumoto, Fujiko; Kanazawa, Kenji; Ohno, Shiro; Morita, Hiroyuki; Ukimura, Akira; Mishima, Nobuhiko; Otsuka, Fumio; Ohyama, Yoshio; Nara, Noriko; Murakami, Kazunari; Mashiba, Kouichi; Akazawa, Kenichiro; Yamamoto, Koji; Tanei, Mika; Yamanouchi, Masashi; Senda, Shoichi; Tazuma, Susumu; Hayashi, Jun

    2015-01-01

    Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers. A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted. This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011. The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/μL than for a WBC count of 4,000-8,000/μL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease. The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.

  14. Fever of Unknown Origin in Children: A 6 year- Experience in a Tertiary Pediatric Egyptian Hospital

    PubMed Central

    Hassan, Rasha H; Fouda, Ashraf E; Kandil, Shaimaa M

    2014-01-01

    Background Fever of unknown origin (FUO) is among the most conditions which poses challenge in diagnosis. The presence of information on regional patterns of FUO will shorten the time for diagnosis and reduces health services costs. There are almost no previous studies describing the etiology of FUO in children of Egypt or nearby countries. Aim of the Study To determine different causes of FUO and the possible diagnostic procedures. Methods Data of patients with FUO, presented to the Infectious Diseases Unit of Mansoura University Children Hospital, were retrospectively collected in a 6 year-period from May 2006 to May 2011. The study included children with a fever of 38.3° C or more documented by a health care provider and for which the cause could not be identified after 3 weeks of evaluation as an outpatient or after a week of evaluation in hospital. Patients were then categorized into 5 groups. Results 127 patients met the diagnostic criteria. Infectious diseases were the commonest causes of FUO in 46 cases (36.22%) followed by the miscellaneous causes in 38 cases (29.9%). Meanwhile, collagen vascular diseases and malignancy were diagnosed in 13 cases (10.2%) and 10 cases (7.87%) respectively. While, 20 cases (15.75%) remained undiagnosed. Conclusions Infectious diseases are the commonest cause of FUO. The delay in diagnosis was due to atypical presentations or inappropriate use of antibiotic prior to the referral. Non infectious causes, malignancy and collagen or vascular disorders were diagnosed in rest of the patients. However, about 15% of our patients remained undiagnosed. The diagnosis was established by non-invasive means in more than two-third of the cases. PMID:24899875

  15. [Integrated DNA barcoding database for identifying Chinese animal medicine].

    PubMed

    Shi, Lin-Chun; Yao, Hui; Xie, Li-Fang; Zhu, Ying-Jie; Song, Jing-Yuan; Zhang, Hui; Chen, Shi-Lin

    2014-06-01

    In order to construct an integrated DNA barcoding database for identifying Chinese animal medicine, the authors and their cooperators have completed a lot of researches for identifying Chinese animal medicines using DNA barcoding technology. Sequences from GenBank have been analyzed simultaneously. Three different methods, BLAST, barcoding gap and Tree building, have been used to confirm the reliabilities of barcode records in the database. The integrated DNA barcoding database for identifying Chinese animal medicine has been constructed using three different parts: specimen, sequence and literature information. This database contained about 800 animal medicines and the adulterants and closely related species. Unknown specimens can be identified by pasting their sequence record into the window on the ID page of species identification system for traditional Chinese medicine (www. tcmbarcode. cn). The integrated DNA barcoding database for identifying Chinese animal medicine is significantly important for animal species identification, rare and endangered species conservation and sustainable utilization of animal resources.

  16. 12. Photocopy of lithograph (source unknown) The Armor Lithograph Company, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Photocopy of lithograph (source unknown) The Armor Lithograph Company, Ltd., Pittsburgh, Pennsylvania, ca. 1888 COURTHOUSE AND JAIL, FROM THE WEST - Allegheny County Courthouse & Jail, 436 Grant Street (Courthouse), 420 Ross Street (Jail), Pittsburgh, Allegheny County, PA

  17. 11. Photocopy of photograph (from St. Paul's Church) Photographer unknown ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Photocopy of photograph (from St. Paul's Church) Photographer unknown 1886 'EPISCOPAL CHURCH, CORNER OF 1ST AND J ST. BENICIA' WEST AND SOUTH SIDES - St. Paul's Episcopal Church, 120 East J Street, Benicia, Solano County, CA

  18. [Focal myositis: An unknown disease].

    PubMed

    Gallay, L; Streichenberger, N; Benveniste, O; Allenbach, Y

    2017-10-01

    Focal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual. Copyright © 2017. Published by Elsevier SAS.

  19. 2. Photocopy of photograph (location of original unknown) Mary Mather, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Photocopy of photograph (location of original unknown) Mary Mather, photographer, ca. 1920 GENERAL VIEW OF WEST (LEFT) AND SOUTH (RIGHT) FACADES, TAKEN FROM LEVEE - Bagatelle Plantation, East River Road (moved to Iberville Parish), Donaldsonville, Ascension Parish, LA

  20. Preparation and Identification of Benzoic Acids and Benzamides: An Organic "Unknown" Lab

    NASA Astrophysics Data System (ADS)

    Taber, Douglass F.; Nelson, Jade D.; Northrop, John P.

    1999-06-01

    The reaction of an unknown substituted benzene derivative (illustrated by toluene) with oxalyl chloride and aluminum chloride gives the acid chloride. Hydrolysis of the acid chloride gives the acid, and reaction of the acid with concentrated aqueous ammonia gives the benzamide.

    The equivalent weight of the acid can be determined by titration with standardized aqueous sodium hydroxide. Given this information and the melting points of the acid and the benzamide, it is possible to deduce the structure of the initial unknown.

  1. Gene expression profile and immunological evaluation of unique hypothetical unknown proteins of Mycobacterium leprae by using quantitative real-time PCR.

    PubMed

    Kim, Hee Jin; Prithiviraj, Kalyani; Groathouse, Nathan; Brennan, Patrick J; Spencer, John S

    2013-02-01

    The cell-mediated immunity (CMI)-based in vitro gamma interferon release assay (IGRA) of Mycobacterium leprae-specific antigens has potential as a promising diagnostic means to detect those individuals in the early stages of M. leprae infection. Diagnosis of leprosy is a major obstacle toward ultimate disease control and has been compromised in the past by the lack of specific markers. Comparative bioinformatic analysis among mycobacterial genomes identified potential M. leprae-specific proteins called "hypothetical unknowns." Due to massive gene decay and the prevalence of pseudogenes, it is unclear whether any of these proteins are expressed or are immunologically relevant. In this study, we performed cDNA-based quantitative real-time PCR to investigate the expression status of 131 putative open reading frames (ORFs) encoding hypothetical unknowns. Twenty-six of the M. leprae-specific antigen candidates showed significant levels of gene expression compared to that of ESAT-6 (ML0049), which is an important T cell antigen of low abundance in M. leprae. Fifteen of 26 selected antigen candidates were expressed and purified in Escherichia coli. The seroreactivity to these proteins of pooled sera from lepromatous leprosy patients and cavitary tuberculosis patients revealed that 9 of 15 recombinant hypothetical unknowns elicited M. leprae-specific immune responses. These nine proteins may be good diagnostic reagents to improve both the sensitivity and specificity of detection of individuals with asymptomatic leprosy.

  2. 48. Photographer unknown February 1925 MENDOCINO COUNTY, SECTION K, HIGHWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    48. Photographer unknown February 1925 MENDOCINO COUNTY, SECTION K, HIGHWAY 1. 1-MEN-1-K #39, LOG GUARD RAIL, 2-25. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  3. 41. Photocopy of photograph (Pentran file), photographer and date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. Photocopy of photograph (Pentran file), photographer and date unknown. Shows trolley with Trolley Barn and Administration Building in background. VIEW NORTHEAST - Newport News & Old Point Railway & Electric Company, Trolley Barn & Administration Building, 3400 Victoria Boulevard, Hampton, Hampton, VA

  4. Three-dimensional cinematography with control object of unknown shape.

    PubMed

    Dapena, J; Harman, E A; Miller, J A

    1982-01-01

    A technique for reconstruction of three-dimensional (3D) motion which involves a simple filming procedure but allows the deduction of coordinates in large object volumes was developed. Internal camera parameters are calculated from measurements of the film images of two calibrated crosses while external camera parameters are calculated from the film images of points in a control object of unknown shape but at least one known length. The control object, which includes the volume in which the activity is to take place, is formed by a series of poles placed at unknown locations, each carrying two targets. From the internal and external camera parameters, and from locations of the images of point in the films of the two cameras, 3D coordinates of the point can be calculated. Root mean square errors of the three coordinates of points in a large object volume (5m x 5m x 1.5m) were 15 mm, 13 mm, 13 mm and 6 mm, and relative errors in lengths averaged 0.5%, 0.7% and 0.5%, respectively.

  5. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

    PubMed Central

    Guo, Xiuqing; Franceschini, Nora; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K.; Li, Changwei; Schwander, Karen; Richard, Melissa A.; Noordam, Raymond; Aschard, Hugues; Bartz, Traci M.; Bielak, Lawrence F.; Dorajoo, Rajkumar; Fisher, Virginia; Hartwig, Fernando P.; Horimoto, Andrea R. V. R.; Lohman, Kurt K.; Manning, Alisa K.; Rankinen, Tuomo; Smith, Albert V.; Wojczynski, Mary K.; Alver, Maris; Boissel, Mathilde; Cai, Qiuyin; Divers, Jasmin; Gao, Chuan; Goel, Anuj; Harris, Sarah E.; He, Meian; Hsu, Fang-Chi; Jackson, Anne U.; Kähönen, Mika; Kasturiratne, Anuradhani; Komulainen, Pirjo; Kühnel, Brigitte; Laguzzi, Federica; Luan, Jian'an; Nolte, Ilja M.; Padmanabhan, Sandosh; Robino, Antonietta; Scott, Robert A.; Sofer, Tamar; Stančáková, Alena; Takeuchi, Fumihiko; Tayo, Bamidele O.; Varga, Tibor V.; Vitart, Veronique; Wang, Yajuan; Warren, Helen R.; Wen, Wanqing; Yanek, Lisa R.; Zhang, Weihua; Zhao, Jing Hua; Afaq, Saima; Amin, Najaf; Arking, Dan E.; Aung, Tin; Boerwinkle, Eric; Borecki, Ingrid; Broeckel, Ulrich; Brown, Morris; Brumat, Marco; Burke, Gregory L.; Chakravarti, Aravinda; Charumathi, Sabanayagam; Ida Chen, Yii-Der; Connell, John M.; Correa, Adolfo; de las Fuentes, Lisa; de Mutsert, Renée; de Silva, H. Janaka; Deng, Xuan; Ding, Jingzhong; Duan, Qing; Eaton, Charles B.; Ehret, Georg; Eppinga, Ruben N.; Faul, Jessica D.; Felix, Stephan B.; Forouhi, Nita G.; Forrester, Terrence; Franco, Oscar H.; Friedlander, Yechiel; Gandin, Ilaria; Gao, He; Ghanbari, Mohsen; Gigante, Bruna; Gu, C. Charles; Gu, Dongfeng; Hagenaars, Saskia P.; Hallmans, Göran; Harris, Tamara B.; He, Jiang; Heng, Chew-Kiat; Hirata, Makoto; Howard, Barbara V.; Ikram, M. Arfan; John, Ulrich; Katsuya, Tomohiro; Khor, Chiea Chuen; Kilpeläinen, Tuomas O.; Koh, Woon-Puay; Krieger, José E.; Kritchevsky, Stephen B.; Kubo, Michiaki; Kuusisto, Johanna; Lakka, Timo A.; Langefeld, Carl D.; Langenberg, Claudia; Launer, Lenore J.; Lehne, Benjamin; Lewis, Cora E.; Li, Yize; Lin, Shiow; Liu, Jianjun; Liu, Jingmin; Loh, Marie; Louie, Tin; Mägi, Reedik; McKenzie, Colin A.; Meitinger, Thomas; Milaneschi, Yuri; Milani, Lili; Mohlke, Karen L.; Momozawa, Yukihide; Nalls, Mike A.; Nelson, Christopher P.; Sotoodehnia, Nona; Norris, Jill M.; O'Connell, Jeff R.; Palmer, Nicholette D.; Perls, Thomas; Pedersen, Nancy L.; Peters, Annette; Peyser, Patricia A.; Poulter, Neil; Raffel, Leslie J.; Raitakari, Olli T.; Roll, Kathryn; Rose, Lynda M.; Rosendaal, Frits R.; Rotter, Jerome I.; Schmidt, Carsten O.; Schreiner, Pamela J.; Schupf, Nicole; Scott, William R.; Shi, Yuan; Sidney, Stephen; Sims, Mario; Sitlani, Colleen M.; Smith, Jennifer A.; Snieder, Harold; Starr, John M.; Strauch, Konstantin; Stringham, Heather M.; Tan, Nicholas Y. Q.; Tang, Hua; Taylor, Kent D.; Teo, Yik Ying; Tham, Yih Chung; Turner, Stephen T.; Uitterlinden, André G.; Vollenweider, Peter; Waldenberger, Melanie; Wang, Lihua; Wang, Ya Xing; Wei, Wen Bin; Williams, Christine; Yao, Jie; Yu, Caizheng; Yuan, Jian-Min; Zhao, Wei; Zonderman, Alan B.; Becker, Diane M.; Boehnke, Michael; Bowden, Donald W.; Chambers, John C.; Deary, Ian J.; Esko, Tõnu; Farrall, Martin; Franks, Paul W.; Freedman, Barry I.; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Kamatani, Yoichiro; Kato, Norihiro; Kooner, Jaspal S.; Kutalik, Zoltán; Laakso, Markku; Laurie, Cathy C.; Leander, Karin; Lehtimäki, Terho; Study, Lifelines Cohort; Magnusson, Patrik K. E.; Oldehinkel, Albertine J.; Penninx, Brenda W. J. H.; Polasek, Ozren; Porteous, David J.; Rauramaa, Rainer; Samani, Nilesh J.; Scott, James; Shu, Xiao-Ou; van der Harst, Pim; Wagenknecht, Lynne E.; Watkins, Hugh; Weir, David R.; Wickremasinghe, Ananda R.; Wu, Tangchun; Zheng, Wei; Bouchard, Claude; Christensen, Kaare; Evans, Michele K.; Gudnason, Vilmundur; Horta, Bernardo L.; Kardia, Sharon L. R.; Liu, Yongmei; Pereira, Alexandre C.; Psaty, Bruce M.; Ridker, Paul M.; van Dam, Rob M.; Gauderman, W. James; Zhu, Xiaofeng; Mook-Kanamori, Dennis O.; Fornage, Myriam; Rotimi, Charles N.; Cupples, L. Adrienne; Kelly, Tanika N.; Fox, Ervin R.; Hayward, Caroline; van Duijn, Cornelia M.; Tai, E Shyong; Wong, Tien Yin; Kooperberg, Charles; Palmas, Walter; Morrison, Alanna C.; Caulfield, Mark J.; Munroe, Patricia B.; Rao, Dabeeru C.; Province, Michael A.; Levy, Daniel

    2018-01-01

    Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10−5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10−8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension. PMID:29912962

  6. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

    PubMed

    Feitosa, Mary F; Kraja, Aldi T; Chasman, Daniel I; Sung, Yun J; Winkler, Thomas W; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K; Li, Changwei; Bentley, Amy R; Brown, Michael R; Schwander, Karen; Richard, Melissa A; Noordam, Raymond; Aschard, Hugues; Bartz, Traci M; Bielak, Lawrence F; Dorajoo, Rajkumar; Fisher, Virginia; Hartwig, Fernando P; Horimoto, Andrea R V R; Lohman, Kurt K; Manning, Alisa K; Rankinen, Tuomo; Smith, Albert V; Tajuddin, Salman M; Wojczynski, Mary K; Alver, Maris; Boissel, Mathilde; Cai, Qiuyin; Campbell, Archie; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gao, Chuan; Goel, Anuj; Hagemeijer, Yanick; Harris, Sarah E; He, Meian; Hsu, Fang-Chi; Jackson, Anne U; Kähönen, Mika; Kasturiratne, Anuradhani; Komulainen, Pirjo; Kühnel, Brigitte; Laguzzi, Federica; Luan, Jian'an; Matoba, Nana; Nolte, Ilja M; Padmanabhan, Sandosh; Riaz, Muhammad; Rueedi, Rico; Robino, Antonietta; Said, M Abdullah; Scott, Robert A; Sofer, Tamar; Stančáková, Alena; Takeuchi, Fumihiko; Tayo, Bamidele O; van der Most, Peter J; Varga, Tibor V; Vitart, Veronique; Wang, Yajuan; Ware, Erin B; Warren, Helen R; Weiss, Stefan; Wen, Wanqing; Yanek, Lisa R; Zhang, Weihua; Zhao, Jing Hua; Afaq, Saima; Amin, Najaf; Amini, Marzyeh; Arking, Dan E; Aung, Tin; Boerwinkle, Eric; Borecki, Ingrid; Broeckel, Ulrich; Brown, Morris; Brumat, Marco; Burke, Gregory L; Canouil, Mickaël; Chakravarti, Aravinda; Charumathi, Sabanayagam; Ida Chen, Yii-Der; Connell, John M; Correa, Adolfo; de Las Fuentes, Lisa; de Mutsert, Renée; de Silva, H Janaka; Deng, Xuan; Ding, Jingzhong; Duan, Qing; Eaton, Charles B; Ehret, Georg; Eppinga, Ruben N; Evangelou, Evangelos; Faul, Jessica D; Felix, Stephan B; Forouhi, Nita G; Forrester, Terrence; Franco, Oscar H; Friedlander, Yechiel; Gandin, Ilaria; Gao, He; Ghanbari, Mohsen; Gigante, Bruna; Gu, C Charles; Gu, Dongfeng; Hagenaars, Saskia P; Hallmans, Göran; Harris, Tamara B; He, Jiang; Heikkinen, Sami; Heng, Chew-Kiat; Hirata, Makoto; Howard, Barbara V; Ikram, M Arfan; John, Ulrich; Katsuya, Tomohiro; Khor, Chiea Chuen; Kilpeläinen, Tuomas O; Koh, Woon-Puay; Krieger, José E; Kritchevsky, Stephen B; Kubo, Michiaki; Kuusisto, Johanna; Lakka, Timo A; Langefeld, Carl D; Langenberg, Claudia; Launer, Lenore J; Lehne, Benjamin; Lewis, Cora E; Li, Yize; Lin, Shiow; Liu, Jianjun; Liu, Jingmin; Loh, Marie; Louie, Tin; Mägi, Reedik; McKenzie, Colin A; Meitinger, Thomas; Metspalu, Andres; Milaneschi, Yuri; Milani, Lili; Mohlke, Karen L; Momozawa, Yukihide; Nalls, Mike A; Nelson, Christopher P; Sotoodehnia, Nona; Norris, Jill M; O'Connell, Jeff R; Palmer, Nicholette D; Perls, Thomas; Pedersen, Nancy L; Peters, Annette; Peyser, Patricia A; Poulter, Neil; Raffel, Leslie J; Raitakari, Olli T; Roll, Kathryn; Rose, Lynda M; Rosendaal, Frits R; Rotter, Jerome I; Schmidt, Carsten O; Schreiner, Pamela J; Schupf, Nicole; Scott, William R; Sever, Peter S; Shi, Yuan; Sidney, Stephen; Sims, Mario; Sitlani, Colleen M; Smith, Jennifer A; Snieder, Harold; Starr, John M; Strauch, Konstantin; Stringham, Heather M; Tan, Nicholas Y Q; Tang, Hua; Taylor, Kent D; Teo, Yik Ying; Tham, Yih Chung; Turner, Stephen T; Uitterlinden, André G; Vollenweider, Peter; Waldenberger, Melanie; Wang, Lihua; Wang, Ya Xing; Wei, Wen Bin; Williams, Christine; Yao, Jie; Yu, Caizheng; Yuan, Jian-Min; Zhao, Wei; Zonderman, Alan B; Becker, Diane M; Boehnke, Michael; Bowden, Donald W; Chambers, John C; Deary, Ian J; Esko, Tõnu; Farrall, Martin; Franks, Paul W; Freedman, Barry I; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Jonas, Jost Bruno; Kamatani, Yoichiro; Kato, Norihiro; Kooner, Jaspal S; Kutalik, Zoltán; Laakso, Markku; Laurie, Cathy C; Leander, Karin; Lehtimäki, Terho; Study, Lifelines Cohort; Magnusson, Patrik K E; Oldehinkel, Albertine J; Penninx, Brenda W J H; Polasek, Ozren; Porteous, David J; Rauramaa, Rainer; Samani, Nilesh J; Scott, James; Shu, Xiao-Ou; van der Harst, Pim; Wagenknecht, Lynne E; Wareham, Nicholas J; Watkins, Hugh; Weir, David R; Wickremasinghe, Ananda R; Wu, Tangchun; Zheng, Wei; Bouchard, Claude; Christensen, Kaare; Evans, Michele K; Gudnason, Vilmundur; Horta, Bernardo L; Kardia, Sharon L R; Liu, Yongmei; Pereira, Alexandre C; Psaty, Bruce M; Ridker, Paul M; van Dam, Rob M; Gauderman, W James; Zhu, Xiaofeng; Mook-Kanamori, Dennis O; Fornage, Myriam; Rotimi, Charles N; Cupples, L Adrienne; Kelly, Tanika N; Fox, Ervin R; Hayward, Caroline; van Duijn, Cornelia M; Tai, E Shyong; Wong, Tien Yin; Kooperberg, Charles; Palmas, Walter; Rice, Kenneth; Morrison, Alanna C; Elliott, Paul; Caulfield, Mark J; Munroe, Patricia B; Rao, Dabeeru C; Province, Michael A; Levy, Daniel

    2018-01-01

    Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

  7. Integrating Gene Expression with Summary Association Statistics to Identify Genes Associated with 30 Complex Traits.

    PubMed

    Mancuso, Nicholas; Shi, Huwenbo; Goddard, Pagé; Kichaev, Gleb; Gusev, Alexander; Pasaniuc, Bogdan

    2017-03-02

    Although genome-wide association studies (GWASs) have identified thousands of risk loci for many complex traits and diseases, the causal variants and genes at these loci remain largely unknown. Here, we introduce a method for estimating the local genetic correlation between gene expression and a complex trait and utilize it to estimate the genetic correlation due to predicted expression between pairs of traits. We integrated gene expression measurements from 45 expression panels with summary GWAS data to perform 30 multi-tissue transcriptome-wide association studies (TWASs). We identified 1,196 genes whose expression is associated with these traits; of these, 168 reside more than 0.5 Mb away from any previously reported GWAS significant variant. We then used our approach to find 43 pairs of traits with significant genetic correlation at the level of predicted expression; of these, eight were not found through genetic correlation at the SNP level. Finally, we used bi-directional regression to find evidence that BMI causally influences triglyceride levels and that triglyceride levels causally influence low-density lipoprotein. Together, our results provide insight into the role of gene expression in the susceptibility of complex traits and diseases. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Unknown loads affect force production capacity in early phases of bench press throws.

    PubMed

    Hernández Davó, J L; Sabido Solana, R; Sarabia Marínm, J M; Sánchez Martos, Á; Moya Ramón, M

    2015-10-01

    Explosive strength training aims to improve force generation in early phases of movement due to its importance in sport performance. The present study examined the influence of lack of knowledge about the load lifted in explosive parameters during bench press throws. Thirteen healthy young men (22.8±2.0 years) participated in the study. Participants performed bench press throws with three different loads (30, 50 and 70% of 1 repetition maximum) in two different conditions (known and unknown loads). In unknown condition, loads were changed within sets in each repetition and participants did not know the load, whereas in known condition the load did not change within sets and participants had knowledge about the load lifted. Results of repeated-measures ANOVA revealed that unknown conditions involves higher power in the first 30, 50, 100 and 150 ms with the three loads, higher values of ratio of force development in those first instants, and differences in time to reach maximal rate of force development with 50 and 70% of 1 repetition maximum. This study showed that unknown conditions elicit higher values of explosive parameters in early phases of bench press throws, thereby this kind of methodology could be considered in explosive strength training.

  9. Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis

    PubMed Central

    Alamgir, Md; Eroukova, Veronika; Jessulat, Matthew; Xu, Jianhua; Golshani, Ashkan

    2008-01-01

    Background Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s) for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, ~4700 strains) for increased sensitivity to paromomycin, which targets the process of protein synthesis. Results As expected, our analysis indicated that the majority of deletion strains (134) with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45), cellular component biogenesis and organization (28), DNA maintenance (21), transport (20), others (38) and unknown (39). These may represent minor cellular target sites (side-effects) for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. Conclusion We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s). PMID:19055778

  10. Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis.

    PubMed

    Alamgir, Md; Eroukova, Veronika; Jessulat, Matthew; Xu, Jianhua; Golshani, Ashkan

    2008-12-03

    Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s) for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, approximately 4700 strains) for increased sensitivity to paromomycin, which targets the process of protein synthesis. As expected, our analysis indicated that the majority of deletion strains (134) with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45), cellular component biogenesis and organization (28), DNA maintenance (21), transport (20), others (38) and unknown (39). These may represent minor cellular target sites (side-effects) for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s).

  11. Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: A multicenter retrospective cohort study.

    PubMed

    Fujimoto, Daichi; Yoshioka, Hiroshige; Kataoka, Yuki; Morimoto, Takeshi; Kim, Young Hak; Tomii, Keisuke; Ishida, Tadashi; Hirabayashi, Masataka; Hara, Satoshi; Ishitoko, Manabu; Fukuda, Yasushi; Hwang, Moon Hee; Sakai, Naoki; Fukui, Motonari; Nakaji, Hitoshi; Morita, Mitsunori; Mio, Tadashi; Yasuda, Takehiro; Sugita, Takakazu; Hirai, Toyohiro

    2018-05-01

    Nivolumab has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials. We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016. Of 613 patients included in our study, 141 had poor performance status (PS) and 106 were EGFR mutation - or ALK rearrangement-positive. The response and disease control rates were 20% and 44%, respectively; the estimated 1-year progression-free survival (PFS) was 18%. Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK rearrangement as independent negative predictors of PFS. The most frequently reported grade ≥3 adverse event was pneumonitis (5% of patients). Severe pneumonitis (grade ≥3) occurred significantly earlier than mild pneumonitis (1.6 vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months, respectively; P = 0.002). Smoking status, PS, and EGFR mutation/ALK rearrangement were independent predictors of PFS. Our study elucidated nivolumab's efficacy in previously underreported patient populations; i.e., those with poor PS and/or with driver oncogenes. We also found that pneumonitis is not infrequent, and carries key implications for outcomes. These data should be useful for improving the clinical courses of nivolumab-treated patients with NSCLC. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. 17. Photocopy of a photograph, source and date unknown GENERAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. Photocopy of a photograph, source and date unknown GENERAL VIEW OF FRONT FACADE OF MT. CLARE STATION; PASSENGER CAR SHOP IN REAR - Baltimore & Ohio Railroad, Mount Clare Passenger Car Shop, Southwest corner of Pratt & Poppleton Streets, Baltimore, Independent City, MD

  13. Carcinoma of Unknown Primary Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Carcinoma of unknown primary (CUP) treatment depends on the best determination of the primary site, if possible. Treatment options may include surgery, radiation therapy, and systemic treatment. Get detailed information about diagnosis and treatment of CUP in this summary for clinicians.

  14. 42. Photocopy of photograph, photographer unknown, 12 September 1928 (original ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    42. Photocopy of photograph, photographer unknown, 12 September 1928 (original print located at Arizona Department of Transportation, Phoenix AZ). BRIDGE IMMEDIATELY AFTER INSERTION OF CENTER PIN. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  15. 42. Photocopy of photograph (Pentran file), photographer and date unknown ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    42. Photocopy of photograph (Pentran file), photographer and date unknown (circa 1950). Shows Trolley Barn in background and Administration Building on right. VIEW SOUTH - Newport News & Old Point Railway & Electric Company, Trolley Barn & Administration Building, 3400 Victoria Boulevard, Hampton, Hampton, VA

  16. 54. Photographer unknown February 1925 HUMBOLDT COUNTY, SECTION J, HIGHWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    54. Photographer unknown February 1925 HUMBOLDT COUNTY, SECTION J, HIGHWAY 1. HUM-1-J #34, SINKS ALONG HIGH. NEAR OCEAN, 2-25. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  17. Iron overload patients with unknown etiology from national survey in Japan.

    PubMed

    Ikuta, Katsuya; Hatayama, Mayumi; Addo, Lynda; Toki, Yasumichi; Sasaki, Katsunori; Tatsumi, Yasuaki; Hattori, Ai; Kato, Ayako; Kato, Koichi; Hayashi, Hisao; Suzuki, Takahiro; Kobune, Masayoshi; Tsutsui, Miyuki; Gotoh, Akihiko; Aota, Yasuo; Matsuura, Motoo; Hamada, Yuzuru; Tokuda, Takahiro; Komatsu, Norio; Kohgo, Yutaka

    2017-03-01

    Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

  18. Characterizing heterogeneous properties of cerebral aneurysms with unknown stress-free geometry: a precursor to in vivo identification.

    PubMed

    Zhao, Xuefeng; Raghavan, Madhavan L; Lu, Jia

    2011-05-01

    Knowledge of elastic properties of cerebral aneurysms is crucial for understanding the biomechanical behavior of the lesion. However, characterizing tissue properties using in vivo motion data presents a tremendous challenge. Aside from the limitation of data accuracy, a pressing issue is that the in vivo motion does not expose the stress-free geometry. This is compounded by the nonlinearity, anisotropy, and heterogeneity of the tissue behavior. This article introduces a method for identifying the heterogeneous properties of aneurysm wall tissue under unknown stress-free configuration. In the proposed approach, an accessible configuration is taken as the reference; the unknown stress-free configuration is represented locally by a metric tensor describing the prestrain from the stress-free configuration to the reference configuration. Material parameters are identified together with the metric tensor pointwisely. The paradigm is tested numerically using a forward-inverse analysis loop. An image-derived sac is considered. The aneurysm tissue is modeled as an eightply laminate whose constitutive behavior is described by an anisotropic hyperelastic strain-energy function containing four material parameters. The parameters are assumed to vary continuously in two assigned patterns to represent two types of material heterogeneity. Nine configurations between the diastolic and systolic pressures are generated by forward quasi-static finite element analyses. These configurations are fed to the inverse analysis to delineate the material parameters and the metric tensor. The recovered and the assigned distributions are in good agreement. A forward verification is conducted by comparing the displacement solutions obtained from the recovered and the assigned material parameters at a different pressure. The nodal displacements are found in excellent agreement.

  19. Teleportation of Unknown Superpositions of Collective Atomic Coherent States

    NASA Astrophysics Data System (ADS)

    Zheng, Shi-Biao

    2001-06-01

    We propose a scheme to teleport an unknown superposition of two atomic coherent states with different phases. Our scheme is based on resonant and dispersive atom-field interaction. Our scheme provides a possibility of teleporting macroscopic superposition states of many atoms first time. The project supported by National Natural Science Foundation of China under Grant No. 60008003

  20. MetaMapR: pathway independent metabolomic network analysis incorporating unknowns.

    PubMed

    Grapov, Dmitry; Wanichthanarak, Kwanjeera; Fiehn, Oliver

    2015-08-15

    Metabolic network mapping is a widely used approach for integration of metabolomic experimental results with biological domain knowledge. However, current approaches can be limited by biochemical domain or pathway knowledge which results in sparse disconnected graphs for real world metabolomic experiments. MetaMapR integrates enzymatic transformations with metabolite structural similarity, mass spectral similarity and empirical associations to generate richly connected metabolic networks. This open source, web-based or desktop software, written in the R programming language, leverages KEGG and PubChem databases to derive associations between metabolites even in cases where biochemical domain or molecular annotations are unknown. Network calculation is enhanced through an interface to the Chemical Translation System, which allows metabolite identifier translation between >200 common biochemical databases. Analysis results are presented as interactive visualizations or can be exported as high-quality graphics and numerical tables which can be imported into common network analysis and visualization tools. Freely available at http://dgrapov.github.io/MetaMapR/. Requires R and a modern web browser. Installation instructions, tutorials and application examples are available at http://dgrapov.github.io/MetaMapR/. ofiehn@ucdavis.edu. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Developing Probabilistic Safety Performance Margins for Unknown and Underappreciated Risks

    NASA Technical Reports Server (NTRS)

    Benjamin, Allan; Dezfuli, Homayoon; Everett, Chris

    2015-01-01

    Probabilistic safety requirements currently formulated or proposed for space systems, nuclear reactor systems, nuclear weapon systems, and other types of systems that have a low-probability potential for high-consequence accidents depend on showing that the probability of such accidents is below a specified safety threshold or goal. Verification of compliance depends heavily upon synthetic modeling techniques such as PRA. To determine whether or not a system meets its probabilistic requirements, it is necessary to consider whether there are significant risks that are not fully considered in the PRA either because they are not known at the time or because their importance is not fully understood. The ultimate objective is to establish a reasonable margin to account for the difference between known risks and actual risks in attempting to validate compliance with a probabilistic safety threshold or goal. In this paper, we examine data accumulated over the past 60 years from the space program, from nuclear reactor experience, from aircraft systems, and from human reliability experience to formulate guidelines for estimating probabilistic margins to account for risks that are initially unknown or underappreciated. The formulation includes a review of the safety literature to identify the principal causes of such risks.

  2. An Alternative Approach to "Identification of Unknowns": Designing a Protocol to Verify the Identities of Nitrogen Fixing Bacteria.

    PubMed

    Martinez-Vaz, Betsy M; Denny, Roxanne; Young, Nevin D; Sadowsky, Michael J

    2015-12-01

    Microbiology courses often include a laboratory activity on the identification of unknown microbes. This activity consists of providing students with microbial cultures and running biochemical assays to identify the organisms. This approach lacks molecular techniques such as sequencing of genes encoding 16S rRNA, which is currently the method of choice for identification of unknown bacteria. A laboratory activity was developed to teach students how to identify microorganisms using 16S rRNA polymerase chain reaction (PCR) and validate microbial identities using biochemical techniques. We hypothesized that designing an experimental protocol to confirm the identity of a bacterium would improve students' knowledge of microbial identification techniques and the physiological characteristics of bacterial species. Nitrogen-fixing bacteria were isolated from the root nodules of Medicago truncatula and prepared for 16S rRNA PCR analysis. Once DNA sequencing revealed the identity of the organisms, the students designed experimental protocols to verify the identity of rhizobia. An assessment was conducted by analyzing pre- and posttest scores and by grading students' verification protocols and presentations. Posttest scores were higher than pretest scores at or below p = 0.001. Normalized learning gains (G) showed an improvement of students' knowledge of microbial identification methods (LO4, G = 0.46), biochemical properties of nitrogen-fixing bacteria (LO3, G = 0.45), and the events leading to the establishment of nitrogen-fixing symbioses (LO1&2, G = 0.51, G = 0.37). An evaluation of verification protocols also showed significant improvement with a p value of less than 0.001.

  3. Realtime motion planning for a mobile robot in an unknown environment using a neurofuzzy based approach

    NASA Astrophysics Data System (ADS)

    Zheng, Taixiong

    2005-12-01

    A neuro-fuzzy network based approach for robot motion in an unknown environment was proposed. In order to control the robot motion in an unknown environment, the behavior of the robot was classified into moving to the goal and avoiding obstacles. Then, according to the dynamics of the robot and the behavior character of the robot in an unknown environment, fuzzy control rules were introduced to control the robot motion. At last, a 6-layer neuro-fuzzy network was designed to merge from what the robot sensed to robot motion control. After being trained, the network may be used for robot motion control. Simulation results show that the proposed approach is effective for robot motion control in unknown environment.

  4. Adenylosuccinate lyase (ADSL) and infantile autism: Absence of previously reported point mutation

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

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

    Autism is a heterogeneous neuropsychiatric syndrome of unknown etiology. There is evidence that a deficiency in the enzyme adenylosuccinate lyase (ADSL), essential for de novo purine biosynthesis, could be involved in the pathogenesis of certain cases. A point mutation in the ADSL gene, resulting in a predicted serine-to-proline substitution and conferring structural instability to the mutant enzyme, has been reported previously in 3 affected siblings. In order to determine the prevalence of the mutation, we PCR-amplified the exon spanning the site of this mutation from the genomic DNA of patients fulfilling DSM-III-R criteria for autistic disorder. None of the 119more » patients tested were found to have this mutation. Furthermore, on preliminary screening using single-strand conformation polymorphism (SSCP), no novel mutations were detected in the coding sequence of four ADSL exons, spanning approximately 50% of the cDNA. In light of these findings, it appears that mutations in the ADSL gene represent a distinctly uncommon cause of autism. 12 refs., 2 figs.« less

  5. Detecting unknown attacks in wireless sensor networks that contain mobile nodes.

    PubMed

    Banković, Zorana; Fraga, David; Moya, José M; Vallejo, Juan Carlos

    2012-01-01

    As wireless sensor networks are usually deployed in unattended areas, security policies cannot be updated in a timely fashion upon identification of new attacks. This gives enough time for attackers to cause significant damage. Thus, it is of great importance to provide protection from unknown attacks. However, existing solutions are mostly concentrated on known attacks. On the other hand, mobility can make the sensor network more resilient to failures, reactive to events, and able to support disparate missions with a common set of sensors, yet the problem of security becomes more complicated. In order to address the issue of security in networks with mobile nodes, we propose a machine learning solution for anomaly detection along with the feature extraction process that tries to detect temporal and spatial inconsistencies in the sequences of sensed values and the routing paths used to forward these values to the base station. We also propose a special way to treat mobile nodes, which is the main novelty of this work. The data produced in the presence of an attacker are treated as outliers, and detected using clustering techniques. These techniques are further coupled with a reputation system, in this way isolating compromised nodes in timely fashion. The proposal exhibits good performances at detecting and confining previously unseen attacks, including the cases when mobile nodes are compromised.

  6. 19. Photographer unknown, circa 1950 'THE LOOP OVER' BRIDGE WAS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Photographer unknown, circa 1950 'THE LOOP OVER' BRIDGE WAS CONSTRUCTED ON NEWFOUND GAP ROAD TO REPLACE A SERIES OF DANGEROUS SWITCHBACKS. THIS ENGINEERING FEATURE QUICKLY BECAME A POPULAR TOURIST ATTRACTION. - Great Smoky Mountains National Park Roads & Bridges, Gatlinburg, Sevier County, TN

  7. 44. Photocopy of photograph, photographer unknown, 1415 June 1929 (original ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    44. Photocopy of photograph, photographer unknown, 14-15 June 1929 (original print located at Utah State Historical Society Photograph Collection, Salt Lake City UT). DEDICATION CEREMONY AT BRIDGE. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  8. 38. Photocopy of photograph (Pentran file), photographer unknown. Bus garage ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. Photocopy of photograph (Pentran file), photographer unknown. Bus garage to left now demolished. Trolley car drivers, maintenance personnel and management staff in 1915. VIEW SOUTH - Newport News & Old Point Railway & Electric Company, Trolley Barn & Administration Building, 3400 Victoria Boulevard, Hampton, Hampton, VA

  9. Photocopy of photograph (from NBPPNSY) photographer unknown, 1988 view east ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of photograph (from NBP-PNSY) photographer unknown, 1988 view east of marine railway (Haer no. Pa-387-W). The railway was being dismantled at the time this photograph was taken. - Naval Base Philadelphia-Philadelphia Naval Shipyard, League Island, Philadelphia, Philadelphia County, PA

  10. Photographic copy of photograph, photographer unknown, 1942 (original print located ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph, photographer unknown, 1942 (original print located at Southern UTE Agency, Bureau of Indian Affairs Office, Ignacio, Colorado). West front and south side of boy's dormitory. - Southern Ute Boarding School, Boy's Dormitory, Ouray & Capote Drives, Ignacio, La Plata County, CO

  11. Photographic copy of photograph, photographer unknown, 1942 (original print located ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph, photographer unknown, 1942 (original print located at Southern UTE Agency, Bureau of Indian Affairs Office, Ignacio, Colorado). East rear and north side of boy's dormitory. - Southern Ute Boarding School, Boy's Dormitory, Ouray & Capote Drives, Ignacio, La Plata County, CO

  12. 188. Photocopy of drawing, Twin Falls Canal Company, date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    188. Photocopy of drawing, Twin Falls Canal Company, date unknown. DETAILS OF GATE RAISING MECHANISM, NO COUNTY; BLUEPRINT. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  13. 45. Photocopy of photograph, photographer unknown, 1415 June 1929 (original ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. Photocopy of photograph, photographer unknown, 14-15 June 1929 (original print located at Arizona Department of Transportation, Phoenix AZ). AIRPLANE STUNT DURING DEDICATION CEREMONY AT BRIDGE. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  14. 4. VIEW NORTHEAST, radar tower (unknown function), prime search radar ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. VIEW NORTHEAST, radar tower (unknown function), prime search radar tower, emergency power building, and height finder radar tower - Fort Custer Military Reservation, P-67 Radar Station, .25 mile north of Dickman Road, east of Clark Road, Battle Creek, Calhoun County, MI

  15. 56. Photographer unknown February 1925 HUMBOLDT COUNTY, SECTION J, HIGHWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    56. Photographer unknown February 1925 HUMBOLDT COUNTY, SECTION J, HIGHWAY 1. HUM-1-J #36, SINKS ALONG OCEAN SHORE, 2-25. Stamped office copy. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  16. Education Through Exploration: Evaluating the Unknown

    NASA Astrophysics Data System (ADS)

    Anbar, A. D.

    2015-12-01

    Mastery of the peculiar and powerful practices of science is increasingly important for the average citizen. With the rise of the Internet, most of human knowledge is at our fingertips. As content becomes a commodity, success and survival aren't about who knows the most, but who is better able to explore the unknown, actively applying and extending knowledge through critical thinking and hypothesis-driven problem-solving. This applies to the economic livelihoods of individuals and to society at large as we grapple with climate change and other science-infused challenges. Unfortunately, science is too often taught as an encyclopedic collection of settled facts to be mastered rather than as a process of exploration that embraces curiosity, inquiry, testing, and communication to reduce uncertainty about the unknown. This problem is exacerbated by the continued prevalence of teacher-centric pedagogy, which promotes learning-from-authority and passive learning. The initial wave of massively open online courses (MOOCs) generally mimic this teaching style in virtual form. It is hypothesized that emerging digital teaching technologies can help address this challenge at Internet scale in "next generation" MOOCs and flipped classroom experiences. Interactive simulations, immersive virtual field trips, gamified elements, rapid adaptive feedback, intelligent tutoring systems, and personalized pathways, should motivate and enhance learning. Through lab-like projects and tutorials, students should be able to construct knowledge from interactive experiences, modeling the authentic practice of science while mastering complex concepts. Freed from lecturing, teaching staff should be available for direct and intense student-teacher interactions. These claims are difficult to evaluate with traditional assessment instruments, but digital technologies provide powerful new ways to evaluate student learning and learn from student behaviors. We will describe ongoing experiences with such

  17. Recent meta-analyses neglect previous systematic reviews and meta-analyses about the same topic: a systematic examination.

    PubMed

    Helfer, Bartosz; Prosser, Aaron; Samara, Myrto T; Geddes, John R; Cipriani, Andrea; Davis, John M; Mavridis, Dimitris; Salanti, Georgia; Leucht, Stefan

    2015-04-14

    As the number of systematic reviews is growing rapidly, we systematically investigate whether meta-analyses published in leading medical journals present an outline of available evidence by referring to previous meta-analyses and systematic reviews. We searched PubMed for recent meta-analyses of pharmacological treatments published in high impact factor journals. Previous systematic reviews and meta-analyses were identified with electronic searches of keywords and by searching reference sections. We analyzed the number of meta-analyses and systematic reviews that were cited, described and discussed in each recent meta-analysis. Moreover, we investigated publication characteristics that potentially influence the referencing practices. We identified 52 recent meta-analyses and 242 previous meta-analyses on the same topics. Of these, 66% of identified previous meta-analyses were cited, 36% described, and only 20% discussed by recent meta-analyses. The probability of citing a previous meta-analysis was positively associated with its publication in a journal with a higher impact factor (odds ratio, 1.49; 95% confidence interval, 1.06 to 2.10) and more recent publication year (odds ratio, 1.19; 95% confidence interval 1.03 to 1.37). Additionally, the probability of a previous study being described by the recent meta-analysis was inversely associated with the concordance of results (odds ratio, 0.38; 95% confidence interval, 0.17 to 0.88), and the probability of being discussed was increased for previous studies that employed meta-analytic methods (odds ratio, 32.36; 95% confidence interval, 2.00 to 522.85). Meta-analyses on pharmacological treatments do not consistently refer to and discuss findings of previous meta-analyses on the same topic. Such neglect can lead to research waste and be confusing for readers. Journals should make the discussion of related meta-analyses mandatory.

  18. Sliding Mode Observer-Based Current Sensor Fault Reconstruction and Unknown Load Disturbance Estimation for PMSM Driven System.

    PubMed

    Zhao, Kaihui; Li, Peng; Zhang, Changfan; Li, Xiangfei; He, Jing; Lin, Yuliang

    2017-12-06

    This paper proposes a new scheme of reconstructing current sensor faults and estimating unknown load disturbance for a permanent magnet synchronous motor (PMSM)-driven system. First, the original PMSM system is transformed into two subsystems; the first subsystem has unknown system load disturbances, which are unrelated to sensor faults, and the second subsystem has sensor faults, but is free from unknown load disturbances. Introducing a new state variable, the augmented subsystem that has sensor faults can be transformed into having actuator faults. Second, two sliding mode observers (SMOs) are designed: the unknown load disturbance is estimated by the first SMO in the subsystem, which has unknown load disturbance, and the sensor faults can be reconstructed using the second SMO in the augmented subsystem, which has sensor faults. The gains of the proposed SMOs and their stability analysis are developed via the solution of linear matrix inequality (LMI). Finally, the effectiveness of the proposed scheme was verified by simulations and experiments. The results demonstrate that the proposed scheme can reconstruct current sensor faults and estimate unknown load disturbance for the PMSM-driven system.

  19. Compensating Unknown Time-Varying Delay in Opto-Electronic Platform Tracking Servo System.

    PubMed

    Xie, Ruihong; Zhang, Tao; Li, Jiaquan; Dai, Ming

    2017-05-09

    This paper investigates the problem of compensating miss-distance delay in opto-electronic platform tracking servo system. According to the characteristic of LOS (light-of-sight) motion, we setup the Markovian process model and compensate this unknown time-varying delay by feed-forward forecasting controller based on robust H∞ control. Finally, simulation based on double closed-loop PI (Proportion Integration) control system indicates that the proposed method is effective for compensating unknown time-varying delay. Tracking experiments on the opto-electronic platform indicate that RMS (root-mean-square) error is 1.253 mrad when tracking 10° 0.2 Hz signal.

  20. A highly precise frequency-based method for estimating the tension of an inclined cable with unknown boundary conditions

    NASA Astrophysics Data System (ADS)

    Ma, Lin

    2017-11-01

    This paper develops a method for precisely determining the tension of an inclined cable with unknown boundary conditions. First, the nonlinear motion equation of an inclined cable is derived, and a numerical model of the motion of the cable is proposed using the finite difference method. The proposed numerical model includes the sag-extensibility, flexural stiffness, inclination angle and rotational stiffness at two ends of the cable. Second, the influence of the dynamic parameters of the cable on its frequencies is discussed in detail, and a method for precisely determining the tension of an inclined cable is proposed based on the derivatives of the eigenvalues of the matrices. Finally, a multiparameter identification method is developed that can simultaneously identify multiple parameters, including the rotational stiffness at two ends. This scheme is applicable to inclined cables with varying sag, varying flexural stiffness and unknown boundary conditions. Numerical examples indicate that the method provides good precision. Because the parameters of cables other than tension (e.g., the flexural stiffness and rotational stiffness at the ends) are not accurately known in practical engineering, the multiparameter identification method could further improve the accuracy of cable tension measurements.

  1. Accounting for unknown foster dams in the genetic evaluation of embryo transfer progeny.

    PubMed

    Suárez, M J; Munilla, S; Cantet, R J C

    2015-02-01

    Animals born by embryo transfer (ET) are usually not included in the genetic evaluation of beef cattle for preweaning growth if the recipient dam is unknown. This is primarily to avoid potential bias in the estimation of the unknown age of dam. We present a method that allows including records of calves with unknown age of dam. Assumptions are as follows: (i) foster cows belong to the same breed being evaluated, (ii) there is no correlation between the breeding value (BV) of the calf and the maternal BV of the recipient cow, and (iii) cows of all ages are used as recipients. We examine the issue of bias for the fixed level of unknown age of dam (AOD) and propose an estimator of the effect based on classical measurement error theory (MEM) and a Bayesian approach. Using stochastic simulation under random mating or selection, the MEM estimating equations were compared with BLUP in two situations as follows: (i) full information (FI); (ii) missing AOD information on some dams. Predictions of breeding value (PBV) from the FI situation had the smallest empirical average bias followed by PBV obtained without taking measurement error into account. In turn, MEM displayed the highest bias, although the differences were small. On the other hand, MEM showed the smallest MSEP, for either random mating or selection, followed by FI, whereas ignoring measurement error produced the largest MSEP. As a consequence from the smallest MSEP with a relatively small bias, empirical accuracies of PBV were larger for MEM than those for full information, which in turn showed larger accuracies than the situation ignoring measurement error. It is concluded that MEM equations are a useful alternative for analysing weaning weight data when recipient cows are unknown, as it mitigates the effects of bias in AOD by decreasing MSEP. © 2014 Blackwell Verlag GmbH.

  2. Photographic copy of photograph, photographer unknown, August 1912 (original print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph, photographer unknown, August 1912 (original print located at U.S. Bureau of Reclamation Upper Columbia Area Office, Yakima, Washington). "A VIEW OF METHOD OF DAM CONSTRUCTION" - Kachess Dam, Kachess River, 1.5 miles north of Interstate 90, Easton, Kittitas County, WA

  3. 45. Photocopy of photograph (Pentran file), photographer and date unknown ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. Photocopy of photograph (Pentran file), photographer and date unknown (circa 1900). A single truck, solid mahagony car which ran between Hampton, Phoebus and Old Point Comfort. - Newport News & Old Point Railway & Electric Company, Trolley Barn & Administration Building, 3400 Victoria Boulevard, Hampton, Hampton, VA

  4. 197. Photocopy of drawing, Twin Falls, Canal Company, date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    197. Photocopy of drawing, Twin Falls, Canal Company, date unknown. GATE STEMS AND LIFTING DEVICES, NO COUNTY; BLUEPRINT SKETCHES. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  5. 193. Photocopy of Photograph, Twin Falls Canal Company, date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    193. Photocopy of Photograph, Twin Falls Canal Company, date unknown. MILNER DAM PROFILE, TWIN FALLS COUNTY, MILNER, IDAHO; BLUEPRINT. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  6. 186. Photocopy of drawing, Twin Falls Canal Company, date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    186. Photocopy of drawing, Twin Falls Canal Company, date unknown. DRY CREEK RESERVOIR, CASSIA COUNTY (NOW TWIN FALLS COUNTY); MAP. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  7. 191. Photocopy of drawing, Twin Falls Canal Company, date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    191. Photocopy of drawing, Twin Falls Canal Company, date unknown. SPILLWAY GATES, MILNER DAM, TWIN FALLS COUNTY, MILNER, IDAHO; BLUEPRINT. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  8. Photographic copy of photograph, photographer unknown, ca. 1930 (original print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph, photographer unknown, ca. 1930 (original print located at Colorado Historical Society, Denver, Colorado). Overall view of Southern UTE Agency Boarding School, with boys dormitory at center. - Southern Ute Boarding School, Boy's Dormitory, Ouray & Capote Drives, Ignacio, La Plata County, CO

  9. 3. Photocopy of 184060 oil painting, artist unknown (from Chester ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Photocopy of 1840-60 oil painting, artist unknown (from Chester County Historical Society, West Chester, Pennsylvania) Photocopy taken by Ned Goode, July 1958 SOUTH FRONT AND EAST SIDE CIRCA 1850 - West Chester Young Ladies Seminary, 300 Maple Avenue, West Chester, Chester County, PA

  10. 5. VIEW EAST, height finder radar towers, radar tower (unknown ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW EAST, height finder radar towers, radar tower (unknown function), prime search radar tower, operations building, and central heating plant - Fort Custer Military Reservation, P-67 Radar Station, .25 mile north of Dickman Road, east of Clark Road, Battle Creek, Calhoun County, MI

  11. 359. Delineator Unknown April 1935 STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    359. Delineator Unknown April 1935 STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; BRIDGE RAILWAY SAN FRANCISCO LOOP; DETAILS OF VIADUCT; FINAL REPORT; DRG. NO. 92 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  12. 38. Photographic copy of photograph, photographer unknown, 26 March 1915 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. Photographic copy of photograph, photographer unknown, 26 March 1915 (original print located at U.S. Bureau of Reclamation Upper Columbia Area Office, Yakima, Washington). " Dredge after failure of control dam." - Keechelus Dam, Yakima River, 10 miles northwest of Easton, Easton, Kittitas County, WA

  13. 39. Photographic copy of photograph, photographer unknown, 26 March 1915 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    39. Photographic copy of photograph, photographer unknown, 26 March 1915 (original print located at U.S. Bureau of Reclamation Upper Columbia Area Office, Yakima, Washington). "View of control dam after failure." - Keechelus Dam, Yakima River, 10 miles northwest of Easton, Easton, Kittitas County, WA

  14. 403. Delineator Unknown May 2, 1933 STUDY FOR SUSPENSION TOWERS; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    403. Delineator Unknown May 2, 1933 STUDY FOR SUSPENSION TOWERS; SAN FRANCISCO - OAKLAND BAY BRIDGE; TIMOTHY L. PFLUEGER, ARTHUR BROWN JR., JOHN J. DONOVAN; BOARD OF CONSULTING ARCHITECTS; SCHEME 2 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  15. Stochastic Online Learning in Dynamic Networks under Unknown Models

    DTIC Science & Technology

    2016-08-02

    Repeated Game with Incomplete Information, IEEE International Conference on Acoustics, Speech, and Signal Processing. 20-MAR-16, Shanghai, China...in a game theoretic framework for the application of multi-seller dynamic pricing with unknown demand models. We formulated the problem as an...infinitely repeated game with incomplete information and developed a dynamic pricing strategy referred to as Competitive and Cooperative Demand Learning

  16. Coma of unknown origin in the emergency department: implementation of an in-house management routine.

    PubMed

    Braun, Mischa; Schmidt, Wolf Ulrich; Möckel, Martin; Römer, Michael; Ploner, Christoph J; Lindner, Tobias

    2016-04-27

    Coma of unknown origin is an emergency caused by a variety of possibly life-threatening pathologies. Although lethality is high, there are currently no generally accepted management guidelines. We implemented a new interdisciplinary standard operating procedure (SOP) for patients presenting with non-traumatic coma of unknown origin. It includes a new in-house triage process, a new alert call, a new composition of the clinical response team and a new management algorithm (altogether termed "coma alarm"). It is triggered by two simple criteria to be checked with out-of-hospital emergency response teams before the patient arrives. A neurologist in collaboration with an internal specialist leads the in-hospital team. Collaboration with anaesthesiology, trauma surgery and neurosurgery is organised along structured pathways that include standardised laboratory tests and imaging. Patients were prospectively enrolled. We calculated response times as well as sensitivity and false positive rates, thus proportions of over- and undertriaged patients, as quality measures for the implementation in the SOP. During 24 months after implementation, we identified 325 eligible patients. Sensitivity was 60 % initially (months 1-4), then fluctuated between 84 and 94 % (months 5-24). Overtriage never exceeded 15 % and undertriage could be kept low at a maximum of 11 % after a learning period. We achieved a median door-to-CT time of 20 minutes. 85 % of patients needed subsequent ICU treatment, 40 % of which required specialised neuro-ICUs. Our results indicate that our new simple in-house triage criteria may be sufficient to identify eligible patients before arrival. We aimed at ensuring the fastest possible proceedings given high portions of underlying time-sensitive neurological and medical pathologies while using all available resources as purposefully as possible. Our SOP may provide an appropriate tool for efficient management of patients with non-traumatic coma. Our results

  17. Identifiability and Identification of Trace Continuous Pollutant Source

    PubMed Central

    Qu, Hongquan; Liu, Shouwen; Pang, Liping; Hu, Tao

    2014-01-01

    Accidental pollution events often threaten people's health and lives, and a pollutant source is very necessary so that prompt remedial actions can be taken. In this paper, a trace continuous pollutant source identification method is developed to identify a sudden continuous emission pollutant source in an enclosed space. The location probability model is set up firstly, and then the identification method is realized by searching a global optimal objective value of the location probability. In order to discuss the identifiability performance of the presented method, a conception of a synergy degree of velocity fields is presented in order to quantitatively analyze the impact of velocity field on the identification performance. Based on this conception, some simulation cases were conducted. The application conditions of this method are obtained according to the simulation studies. In order to verify the presented method, we designed an experiment and identified an unknown source appearing in the experimental space. The result showed that the method can identify a sudden trace continuous source when the studied situation satisfies the application conditions. PMID:24892041

  18. Identifiability and identification of trace continuous pollutant source.

    PubMed

    Qu, Hongquan; Liu, Shouwen; Pang, Liping; Hu, Tao

    2014-01-01

    Accidental pollution events often threaten people's health and lives, and a pollutant source is very necessary so that prompt remedial actions can be taken. In this paper, a trace continuous pollutant source identification method is developed to identify a sudden continuous emission pollutant source in an enclosed space. The location probability model is set up firstly, and then the identification method is realized by searching a global optimal objective value of the location probability. In order to discuss the identifiability performance of the presented method, a conception of a synergy degree of velocity fields is presented in order to quantitatively analyze the impact of velocity field on the identification performance. Based on this conception, some simulation cases were conducted. The application conditions of this method are obtained according to the simulation studies. In order to verify the presented method, we designed an experiment and identified an unknown source appearing in the experimental space. The result showed that the method can identify a sudden trace continuous source when the studied situation satisfies the application conditions.

  19. Using a New Crustal Thickness Model to Test Previous Candidate Lunar Basins and to Search for New Candidates

    NASA Technical Reports Server (NTRS)

    Meyer, H. M.; Frey, H. V.

    2012-01-01

    A new crustal thickness model was used to test the viability of 110 candidate large lunar basins previously identified using older topographic and crustal thickness data as well as photogeologic data. The new model was also used to search for new candidate lunar basins greater than 300 km in diameter. We eliminated 11 of 27 candidates previously identified in the older crustal thickness model, and found strong evidence for at least 8 new candidates.

  20. 18. AERIAL VIEW OF PRISON COMPLEX, CIRCA 1930s Photographer unknown; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. AERIAL VIEW OF PRISON COMPLEX, CIRCA 1930s Photographer unknown; National Archives and Records Administration photograph No. 18-AN-31716. - New Jersey State Prison, Second & Federal Streets, Trenton, Mercer County, NJ

  1. Chronic Traumatic Encephalopathy: Known Causes, Unknown Effects.

    PubMed

    Iacono, Diego; Shively, Sharon B; Edlow, Brian L; Perl, Daniel P

    2017-05-01

    Chronic traumatic encephalopathy (CTE) is a neuropathologic diagnosis typically made in human brains with a history of repetitive traumatic brain injury (rTBI). It remains unknown whether CTE occurs exclusively after rTBI, or whether a single TBI (sTBI) can cause CTE. Similarly, it is unclear whether impact (eg, motor vehicle accidents) and non-impact (eg, blasts) types of energy transfer trigger divergent or common pathologies. While it is established that a history of rTBI increases the risk of multiple neurodegenerative diseases (eg, dementia, parkinsonism, and CTE), the possible pathophysiologic and molecular mechanisms underlying these risks have yet to be elucidated. Published by Elsevier Inc.

  2. Photographic copy of photograph, photographer unknown, August 1912 (original print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph, photographer unknown, August 1912 (original print located at U.S. Bureau of Reclamation Upper Columbia Area Office, Yakima, Washington). "METHOD OF CONSTRUCTING DAM AFTER REMOVING OF TRESTLE" - Kachess Dam, Kachess River, 1.5 miles north of Interstate 90, Easton, Kittitas County, WA

  3. 6. Photographic copy of photograph. No date. Photographer unknown. (Source: ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Photographic copy of photograph. No date. Photographer unknown. (Source: SCIP office, Coolidge, AZ) CHINA WASH FLUME UNDER CONSTRUCTION - San Carlos Irrigation Project, China Wash Flume, Main (Florence-Case Grande) Canal at Station 137+00, T4S, R10E, S14, Coolidge, Pinal County, AZ

  4. 185. Photocopy of drawing, Twin Falls Canal Company, date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    185. Photocopy of drawing, Twin Falls Canal Company, date unknown. MILNER DAM CROSS SECTION PLAN, TWIN FALLS COUNTY, MILNER, IDAHO; BLUEPRINT. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  5. 195. Photocopy of drawing, Twin Falls Canal Company, date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    195. Photocopy of drawing, Twin Falls Canal Company, date unknown. PLAN OF CONSTRUCTION AREA PLANT, TWIN FALLS COUNTY, MILNER, IDAHO; BLUEPRINT. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  6. 190. Photocopy of drawing, Twin Falls Canal Company, date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    190. Photocopy of drawing, Twin Falls Canal Company, date unknown. GENERAL PLAN OF MILNER DAM TUNNELS, TWIN FALLS COUNTY, MILNER, IDAHO; BLUEPRINT. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  7. Photographic copy of photograph, photographer unknown, ca. 1930 (original print ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photographic copy of photograph, photographer unknown, ca. 1930 (original print located at Colorado Historical Society, Denver, Colorado). Overall views of Southern Ute Agency Boarding School, with boys' dormitory at left of lower view. - Southern Ute Boarding School, Boy's Dormitory, Ouray & Capote Drives, Ignacio, La Plata County, CO

  8. 15. Photocopy of color photograph (Photographer unknown, 1974) SACRISTY ATTIC, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Photocopy of color photograph (Photographer unknown, 1974) SACRISTY ATTIC, LOOKING SOUTHWEST. NOTE RAMMED EARTH WALL (NORTH WALL OF CHANCEL) AT LEFT; HOLES WERE LEFT BY WOODEN BRACES USED TO HOLD WALL FORMS DURING CONSTRUCTION - Church of the Holy Cross, State Route 261, Stateburg, Sumter County, SC

  9. 402. Delineator Unknown May 2, 1933 STUDY FOR SUSPENSION TOWERS; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    402. Delineator Unknown May 2, 1933 STUDY FOR SUSPENSION TOWERS; SAN FRANCISCO - OAKLAND BAY BRIDGE; TIMOTHY L. PFLUEGER, ARTHUR BROWN JR., JOHN J. DONOVAN; BOARD OF CONSULTING ARCHITECTS; SCHEME 1A - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  10. 46. Photographic copy of photograph, photographer unknown, 24 July 1916 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    46. Photographic copy of photograph, photographer unknown, 24 July 1916 (original print located at U.S. Bureau of Reclamation Upper Columbia Area Office, Yakima, Washington). "Scheme for shelter for cransemen on bucyrus steam shovel." - Keechelus Dam, Yakima River, 10 miles northwest of Easton, Easton, Kittitas County, WA

  11. 380. Delineator Unknown December 1932 STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    380. Delineator Unknown December 1932 STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; CABLES & ATTACHMENTS WEST BAY CROSSING; CABLE BANDS; CONTRACT NO. 6A; DRAWING NO. 3 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  12. 385. Delineator Unknown December 1932 STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    385. Delineator Unknown December 1932 STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; SUPERSTRUCTURE - WEST BAY CROSSING; ROCKER POSTS AND BEARING; CONTRACT NO. 6; DRAWINGS NO. 42 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  13. 379. Delineator Unknown December 1932 STATE OF CALIFORNIA; DEPARTMENT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    379. Delineator Unknown December 1932 STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; CABLES AND ATTACHMENTS - WEST BAY CROSSING; SPLAY CASTINGS; CONTRACT NO. 6A; DRAWING NO. 4 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  14. Chronic kidney disease of unknown etiology in agricultural communities.

    PubMed

    Almaguer, Miguel; Herrera, Raúl; Orantes, Carlos M

    2014-04-01

    In recent years, Central America, Egypt, India and Sri Lanka have reported a high prevalence of chronic kidney disease of unknown etiology in agricultural communities, predominantly among male farmworkers. This essay examines the disease's case definitions, epidemiology (disease burden, demographics, associated risk factors) and causal hypotheses, by reviewing published findings from El Salvador, Nicaragua, Costa Rica, Sri Lanka, Egypt and India. The range of confirmed chronic kidney disease prevalence was 17.9%-21.1%. Prevalence of reduced glomerular filtration (<60 mL/min/1.73 m2 body surface area) based on a single serum creatinine measurement was 0%-67% men and 0%-57% women. Prevalence was generally higher in male farmworkers aged 20-50 years, and varied by community economic activity and altitude. Cause was unknown in 57.4%-66.7% of patients. The dominant histopathological diagnosis was chronic tubulointerstitial nephritis. Associations were reported with agricultural work, agrochemical exposure, dehydration, hypertension, homemade alcohol use and family history of chronic kidney disease. There is no strong evidence for a single cause, and multiple environmental, occupational and social factors are probably involved. Further etiological research is needed, plus interventions to reduce preventable risk factors.

  15. [Multiplex Ligation - dependent Probe Amplification (MLPA) as a screening test in children with developmental defects and intellectual disability of unknown etiology].

    PubMed

    Laczmańska, Izabela; Jakubiak, Aleksandra; Slęzak, Ryszard; Pesz, Karolina; Stembalska, Agnieszka; Laczmański, Lukasz; Sąsiadek, Maria M; Smigiel, Robert

    2011-01-01

    Developmental delay and intellectual disability are significant medical and social problems which concern 1-3% of population. The etiology remains unknown in over half of the cases. To evaluate the efficiency of MLPA (Multiplex Ligation-dependent Probe Amplification) as a screening test in diagnosis of patients with developmental delay and/or intellectual disability. 313 MLPA tests were performed in 256 patients with developmental delay and/ or intellectual disability with unknown etiology. MLPA test was made after exclusion of genetic disorders possible to diagnose by dysmorphological examination or using specifi c genetic tests. Positive results were confirmed by FISH analysis with appropriate probes. Chromosomal microaberrations were identifi ed in 15 patients (4,8%): deletions of 1p36 in 4 cases, in one case deletion of 22q11.21, 22q13.33, SNRPN1, 4ptel, 6qtel, 7q11.23, 16ptel, 18qtel as well as one ca se of deletion 3ptel/duplication 15qtel; deletion 18qtel/duplication Xqtel, and also duplication 7q11.23. Detail clinical analysis was performed in patients with diagnosed microaberrations in MLPA test. The molecular MLPA test, screening for chromosomal microaberration syndromes, should be performed in each patient with developmental delay and/or intellectual disability of unknown etiology and normal cytogenetic analysis, even if congenital defects and positive familial history do not exist.

  16. Population-based incidence, treatment and survival of patients with peritoneal metastases of unknown origin.

    PubMed

    Thomassen, Irene; Verhoeven, Rob H A; van Gestel, Yvette R B M; van de Wouw, Agnes J; Lemmens, Valery E P P; de Hingh, Ignace H J T

    2014-01-01

    Until recently, peritoneal metastases (PM) were regarded as an untreatable condition, regardless of the organ of origin. Currently, promising treatment options are available for selected patients with PM from colorectal, appendiceal, ovarian or gastric carcinoma. The aim of this study was to investigate the incidence, treatment and survival of patients presenting with PM in whom the origin of PM remains unknown. Data from patients diagnosed with PM of unknown origin during 1984-2010 were extracted from the Eindhoven Cancer Registry. European age-standardised incidence rates were calculated and data on treatment and survival were analysed. In total 1051 patients were diagnosed with PM of unknown origin. In 606 patients (58%) the peritoneum was the only site of metastasis, and 445 patients also had other metastases. Chemotherapy usage has increased from 8% in the earliest period to 16% in most recent years (p=.016). Median survival was extremely poor with only 42days (95% confidence interval (CI) 39-47days) and did not change over time. Median survival of patients not receiving chemotherapy was significantly worse than of those receiving chemotherapy (36 versus 218days, p<.0001). The prognosis of PM of unknown origin is extremely poor and did not improve over time. Given the recent progress that has been achieved in selected patients presenting with PM, maximum efforts should be undertaken in order to diagnose the origin of PM as accurately as possible. Potentially effective treatment strategies should be further explored for patients in whom the organ of origin remains unknown. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.

    PubMed

    Kim, Young Jin; Go, Min Jin; Hu, Cheng; Hong, Chang Bum; Kim, Yun Kyoung; Lee, Ji Young; Hwang, Joo-Yeon; Oh, Ji Hee; Kim, Dong-Joon; Kim, Nam Hee; Kim, Soeui; Hong, Eun Jung; Kim, Ji-Hyun; Min, Haesook; Kim, Yeonjung; Zhang, Rong; Jia, Weiping; Okada, Yukinori; Takahashi, Atsushi; Kubo, Michiaki; Tanaka, Toshihiro; Kamatani, Naoyuki; Matsuda, Koichi; Park, Taesung; Oh, Bermseok; Kimm, Kuchan; Kang, Daehee; Shin, Chol; Cho, Nam H; Kim, Hyung-Lae; Han, Bok-Ghee; Lee, Jong-Young; Cho, Yoon Shin

    2011-09-11

    To identify the genetic bases for nine metabolic traits, we conducted a meta-analysis combining Korean genome-wide association results from the KARE project (n = 8,842) and the HEXA shared control study (n = 3,703). We verified the associations of the loci selected from the discovery meta-analysis in the replication stage (30,395 individuals from the BioBank Japan genome-wide association study and individuals comprising the Health2 and Shanghai Jiao Tong University Diabetes cohorts). We identified ten genome-wide significant signals newly associated with traits from an overall meta-analysis. The most compelling associations involved 12q24.11 (near MYL2) and 12q24.13 (in C12orf51) for high-density lipoprotein cholesterol, 2p21 (near SIX2-SIX3) for fasting plasma glucose, 19q13.33 (in RPS11) and 6q22.33 (in RSPO3) for renal traits, and 12q24.11 (near MYL2), 12q24.13 (in C12orf51 and near OAS1), 4q31.22 (in ZNF827) and 7q11.23 (near TBL2-BCL7B) for hepatic traits. These findings highlight previously unknown biological pathways for metabolic traits investigated in this study.

  18. Causality Analysis: Identifying the Leading Element in a Coupled Dynamical System

    PubMed Central

    BozorgMagham, Amir E.; Motesharrei, Safa; Penny, Stephen G.; Kalnay, Eugenia

    2015-01-01

    Physical systems with time-varying internal couplings are abundant in nature. While the full governing equations of these systems are typically unknown due to insufficient understanding of their internal mechanisms, there is often interest in determining the leading element. Here, the leading element is defined as the sub-system with the largest coupling coefficient averaged over a selected time span. Previously, the Convergent Cross Mapping (CCM) method has been employed to determine causality and dominant component in weakly coupled systems with constant coupling coefficients. In this study, CCM is applied to a pair of coupled Lorenz systems with time-varying coupling coefficients, exhibiting switching between dominant sub-systems in different periods. Four sets of numerical experiments are carried out. The first three cases consist of different coupling coefficient schemes: I) Periodic–constant, II) Normal, and III) Mixed Normal/Non-normal. In case IV, numerical experiment of cases II and III are repeated with imposed temporal uncertainties as well as additive normal noise. Our results show that, through detecting directional interactions, CCM identifies the leading sub-system in all cases except when the average coupling coefficients are approximately equal, i.e., when the dominant sub-system is not well defined. PMID:26125157

  19. 13-fold resolution gain through turbid layer via translated unknown speckle illumination

    PubMed Central

    Guo, Kaikai; Zhang, Zibang; Jiang, Shaowei; Liao, Jun; Zhong, Jingang; Eldar, Yonina C.; Zheng, Guoan

    2017-01-01

    Fluorescence imaging through a turbid layer holds great promise for various biophotonics applications. Conventional wavefront shaping techniques aim to create and scan a focus spot through the turbid layer. Finding the correct input wavefront without direct access to the target plane remains a critical challenge. In this paper, we explore a new strategy for imaging through turbid layer with a large field of view. In our setup, a fluorescence sample is sandwiched between two turbid layers. Instead of generating one focus spot via wavefront shaping, we use an unshaped beam to illuminate the turbid layer and generate an unknown speckle pattern at the target plane over a wide field of view. By tilting the input wavefront, we raster scan the unknown speckle pattern via the memory effect and capture the corresponding low-resolution fluorescence images through the turbid layer. Different from the wavefront-shaping-based single-spot scanning, the proposed approach employs many spots (i.e., speckles) in parallel for extending the field of view. Based on all captured images, we jointly recover the fluorescence object, the unknown optical transfer function of the turbid layer, the translated step size, and the unknown speckle pattern. Without direct access to the object plane or knowledge of the turbid layer, we demonstrate a 13-fold resolution gain through the turbid layer using the reported strategy. We also demonstrate the use of this technique to improve the resolution of a low numerical aperture objective lens allowing to obtain both large field of view and high resolution at the same time. The reported method provides insight for developing new fluorescence imaging platforms and may find applications in deep-tissue imaging. PMID:29359102

  20. Psorophora (Grabhamia) varinervis (Diptera: Culicidae) morphological description including pupa and fourth-stage larva previously unknown.

    PubMed

    Rossi, Gustavo C; Stein, Marina; Almirón, Walter R

    2008-05-01

    Psorophora (Grabhamia) varinervis Edwards (Diptera: Culicidae) is redescribed in the adult stage. Pupa and fourth-stage larva are described and illustrated for the first time. Information about distribution, bionomics, and taxonomy also is included. Adults of Ps. varinervis can be separated from the closely related species Ps. (Gra.) discolor (Coquillett) on the basis of the wing characters, and the larva by the siphon and antenna characters.