Sample records for discovering rare malfeasors

  1. Strong profiling is not mathematically optimal for discovering rare malfeasors

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

    Press, William H

    2008-01-01

    In a large population of individuals labeled j = 1,2,...,N, governments attempt to find the rare malfeasor j = j, (terrorist, for example) by making use of priors p{sub j} that estimate the probability of individual j being a malfeasor. Societal resources for secondary random screening such as airport search or police investigation are concentrated against individuals with the largest priors. They may call this 'strong profiling' if the concentration is at least proportional to p{sub j} for the largest values. Strong profiling often results in higher probability, but otherwise innocent, individuals being repeatedly subjected to screening. They show heremore » that, entirely apart from considerations of social policy, strong profiling is not mathematically optimal at finding malfeasors. Even if prior probabilities were accurate, their optimal use would be only as roughly the geometric mean between a strong profiling and a completely uniform sampling of the population.« less

  2. [Breast tumor revealed by a gastric metastasis discovered incidentally].

    PubMed

    Moussaoui, Aziz El; Assi, Fadi; Bental, Abdeslam

    2016-01-01

    The gastric metastasis of breast cancer are rare, and their discovery is difficult, because the symptoms is often unspecific or even absent. We report an original case of ductal carcinoma of the breast revealed by a gastric metastasis discovered incidentally.

  3. DISCOVER-AQ

    Atmospheric Science Data Center

    2017-01-31

    ... Relevant Documents:  DISCOVER-AQ - Airborne Science Data for Atmospheric Composition DISCOVER-AQ - NASA Earth ... DISCOVER-AQ - Mission Highlight Featured Articles : Articles featuring DISCOVER-AQ data products SCAR-B ...

  4. [Fahr syndrome discovered following a bacterial meningitis].

    PubMed

    Sbai, H; Smail, L; Hamdani, S; Essatara, Y; Harrandou, M; Khatouf, M; Kanjaa, N

    2008-05-01

    Fahr's disease refers to a rare syndrome characterized by symmetrical and bilateral intracranial calcifications. The basal ganglia and dentate nucleus are the most common site of involvement and most cases present extrapyramidal symptoms. This disease is mostly associated with a phosphocalcic metabolism disorder, especially to hypoparathyroidism. The authors report a case of Fahr syndrome (FS) discovered when a young patient with hypocalcemia and bacterial meningitis had a cerebral CT scan disclosing intracerebral calcifications. She fully recovered after both meningitis and hypocalcemia were treated.

  5. Rare Variant Association Test with Multiple Phenotypes

    PubMed Central

    Lee, Selyeong; Won, Sungho; Kim, Young Jin; Kim, Yongkang; Kim, Bong-Jo; Park, Taesung

    2016-01-01

    Although genome-wide association studies (GWAS) have now discovered thousands of genetic variants associated with common traits, such variants cannot explain the large degree of “missing heritability,” likely due to rare variants. The advent of next generation sequencing technology has allowed rare variant detection and association with common traits, often by investigating specific genomic regions for rare variant effects on a trait. Although multiply correlated phenotypes are often concurrently observed in GWAS, most studies analyze only single phenotypes, which may lessen statistical power. To increase power, multivariate analyses, which consider correlations between multiple phenotypes, can be used. However, few existing multi-variant analyses can identify rare variants for assessing multiple phenotypes. Here, we propose Multivariate Association Analysis using Score Statistics (MAAUSS), to identify rare variants associated with multiple phenotypes, based on the widely used Sequence Kernel Association Test (SKAT) for a single phenotype. We applied MAAUSS to Whole Exome Sequencing (WES) data from a Korean population of 1,058 subjects, to discover genes associated with multiple traits of liver function. We then assessed validation of those genes by a replication study, using an independent dataset of 3,445 individuals. Notably, we detected the gene ZNF620 among five significant genes. We then performed a simulation study to compare MAAUSS's performance with existing methods. Overall, MAAUSS successfully conserved type 1 error rates and in many cases, had a higher power than the existing methods. This study illustrates a feasible and straightforward approach for identifying rare variants correlated with multiple phenotypes, with likely relevance to missing heritability. PMID:28039885

  6. Mining Rare Associations between Biological Ontologies

    PubMed Central

    Benites, Fernando; Simon, Svenja; Sapozhnikova, Elena

    2014-01-01

    The constantly increasing volume and complexity of available biological data requires new methods for their management and analysis. An important challenge is the integration of information from different sources in order to discover possible hidden relations between already known data. In this paper we introduce a data mining approach which relates biological ontologies by mining cross and intra-ontology pairwise generalized association rules. Its advantage is sensitivity to rare associations, for these are important for biologists. We propose a new class of interestingness measures designed for hierarchically organized rules. These measures allow one to select the most important rules and to take into account rare cases. They favor rules with an actual interestingness value that exceeds the expected value. The latter is calculated taking into account the parent rule. We demonstrate this approach by applying it to the analysis of data from Gene Ontology and GPCR databases. Our objective is to discover interesting relations between two different ontologies or parts of a single ontology. The association rules that are thus discovered can provide the user with new knowledge about underlying biological processes or help improve annotation consistency. The obtained results show that produced rules represent meaningful and quite reliable associations. PMID:24404165

  7. Mining rare associations between biological ontologies.

    PubMed

    Benites, Fernando; Simon, Svenja; Sapozhnikova, Elena

    2014-01-01

    The constantly increasing volume and complexity of available biological data requires new methods for their management and analysis. An important challenge is the integration of information from different sources in order to discover possible hidden relations between already known data. In this paper we introduce a data mining approach which relates biological ontologies by mining cross and intra-ontology pairwise generalized association rules. Its advantage is sensitivity to rare associations, for these are important for biologists. We propose a new class of interestingness measures designed for hierarchically organized rules. These measures allow one to select the most important rules and to take into account rare cases. They favor rules with an actual interestingness value that exceeds the expected value. The latter is calculated taking into account the parent rule. We demonstrate this approach by applying it to the analysis of data from Gene Ontology and GPCR databases. Our objective is to discover interesting relations between two different ontologies or parts of a single ontology. The association rules that are thus discovered can provide the user with new knowledge about underlying biological processes or help improve annotation consistency. The obtained results show that produced rules represent meaningful and quite reliable associations.

  8. Creating an effective clinical registry for rare diseases

    PubMed Central

    D’Agnolo, Hedwig MA; Kievit, Wietske; Andrade, Raul J; Karlsen, Tom Hemming; Wedemeyer, Heiner

    2015-01-01

    The exposure of clinicians to patients with rare gastrointestinal diseases is limited. This hurts clinical studies, which impedes accumulation of scientific knowledge on the natural disease course, treatment outcomes and prognosis in these patients. An excellent method to detect patterns on an aggregate level that would not be possible to discover in individual cases, is a registry study. This paper aims to describe a template to create a successful international registry for rare diseases. We focus mainly on rare hepatic diseases, but lessons from this paper serve other fields in medicine, as well. PMID:27403298

  9. Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study.

    PubMed

    Dewey, Frederick E; Murray, Michael F; Overton, John D; Habegger, Lukas; Leader, Joseph B; Fetterolf, Samantha N; O'Dushlaine, Colm; Van Hout, Cristopher V; Staples, Jeffrey; Gonzaga-Jauregui, Claudia; Metpally, Raghu; Pendergrass, Sarah A; Giovanni, Monica A; Kirchner, H Lester; Balasubramanian, Suganthi; Abul-Husn, Noura S; Hartzel, Dustin N; Lavage, Daniel R; Kost, Korey A; Packer, Jonathan S; Lopez, Alexander E; Penn, John; Mukherjee, Semanti; Gosalia, Nehal; Kanagaraj, Manoj; Li, Alexander H; Mitnaul, Lyndon J; Adams, Lance J; Person, Thomas N; Praveen, Kavita; Marcketta, Anthony; Lebo, Matthew S; Austin-Tse, Christina A; Mason-Suares, Heather M; Bruse, Shannon; Mellis, Scott; Phillips, Robert; Stahl, Neil; Murphy, Andrew; Economides, Aris; Skelding, Kimberly A; Still, Christopher D; Elmore, James R; Borecki, Ingrid B; Yancopoulos, George D; Davis, F Daniel; Faucett, William A; Gottesman, Omri; Ritchie, Marylyn D; Shuldiner, Alan R; Reid, Jeffrey G; Ledbetter, David H; Baras, Aris; Carey, David J

    2016-12-23

    The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic health records (EHRs). We sequenced the exomes of 50,726 adult participants in the DiscovEHR study to identify ~4.2 million rare single-nucleotide variants and insertion/deletion events, of which ~176,000 are predicted to result in a loss of gene function. Linking these data to EHR-derived clinical phenotypes, we find clinical associations supporting therapeutic targets, including genes encoding drug targets for lipid lowering, and identify previously unidentified rare alleles associated with lipid levels and other blood level traits. About 3.5% of individuals harbor deleterious variants in 76 clinically actionable genes. The DiscovEHR data set provides a blueprint for large-scale precision medicine initiatives and genomics-guided therapeutic discovery. Copyright © 2016, American Association for the Advancement of Science.

  10. Calocybe cyanea : a rare and beautiful agaric is discovered in Puerto Rico

    Treesearch

    Timothy J. Baroni; Nick W. Legon; Rytas Vilgalys; D. Jean. Lodge

    1999-01-01

    A rare find of Calocybe cyanea from Puerto Rico is described and illustrated. A discussion of all species of Calocybe found in the Caribbean is provided. Since nearly one-half of the described species of Calocybe can be found in the Neotropics (nine out of the 20 or so known taxa), a key to the species of Calocybe which are found in the Neotropics is included.

  11. Discover Earth

    NASA Technical Reports Server (NTRS)

    Steele, Colleen

    1998-01-01

    Discover Earth is a NASA-sponsored project for teachers of grades 5-12, designed to: (1) enhance understanding of the Earth as an integrated system; (2) enhance the interdisciplinary approach to science instruction; and (3) provide classroom materials that focus on those goals. Discover Earth is conducted by the Institute for Global Environmental Strategies in collaboration with Dr. Eric Barron, Director, Earth System Science Center, The Pennsylvania State University; and Dr. Robert Hudson, Chair, the Department of Meteorology, University of Maryland at College Park. The enclosed materials: (1) represent only part of the Discover Earth materials; (2) were developed by classroom teachers who are participating in the Discover Earth project; (3) utilize an investigative approach and on-line data; and (4) can be effectively adjusted to classrooms with greater/without technology access. The Discover Earth classroom materials focus on the Earth system and key issues of global climate change including topics such as the greenhouse effect, clouds and Earth's radiation balance, surface hydrology and land cover, and volcanoes and climate change. All the materials developed to date are available on line at (http://www.strategies.org) You are encouraged to submit comments and recommendations about these materials to the Discover Earth project manager, contact information is listed below. You are welcome to duplicate all these materials.

  12. Pancreatic sarcoidosis discovered during Whipple procedure.

    PubMed

    Cook, Jonathan; Spees, Tanner; Telefus, Phillip; Ranaudo, Jeffrey M; Carryl, Stephen; Xiao, Philip

    2013-04-04

    Pancreatic sarcoidosis is a rare variant of systemic sarcoidosis, with cases described in literature as recently as January 2010. We present here a case of pancreatic involvement with non-caseating granulomas discovered on laparotomy in a patient with a preoperative diagnosis of pancreatic carcinoma. Computer tomography scan without contrast revealed a well-marginated smooth-shaped tumor in the head of the pancreas morphologically consistent with malignancy. During Whipple procedure, the mass was found to be a large lymph node that contained numerous non-caseating granulomas. Radiologically and clinically, non-caseating granulomas of the pancreas are often misdiagnosed as malignant tumor. Special attention given to this differential diagnosis by surgeons, pathologists and clinicians can avoid misdiagnosis and unnecessary treatment. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2013.

  13. Negligible impact of rare autoimmune-locus coding-region variants on missing heritability.

    PubMed

    Hunt, Karen A; Mistry, Vanisha; Bockett, Nicholas A; Ahmad, Tariq; Ban, Maria; Barker, Jonathan N; Barrett, Jeffrey C; Blackburn, Hannah; Brand, Oliver; Burren, Oliver; Capon, Francesca; Compston, Alastair; Gough, Stephen C L; Jostins, Luke; Kong, Yong; Lee, James C; Lek, Monkol; MacArthur, Daniel G; Mansfield, John C; Mathew, Christopher G; Mein, Charles A; Mirza, Muddassar; Nutland, Sarah; Onengut-Gumuscu, Suna; Papouli, Efterpi; Parkes, Miles; Rich, Stephen S; Sawcer, Steven; Satsangi, Jack; Simmonds, Matthew J; Trembath, Richard C; Walker, Neil M; Wozniak, Eva; Todd, John A; Simpson, Michael A; Plagnol, Vincent; van Heel, David A

    2013-06-13

    Genome-wide association studies (GWAS) have identified common variants of modest-effect size at hundreds of loci for common autoimmune diseases; however, a substantial fraction of heritability remains unexplained, to which rare variants may contribute. To discover rare variants and test them for association with a phenotype, most studies re-sequence a small initial sample size and then genotype the discovered variants in a larger sample set. This approach fails to analyse a large fraction of the rare variants present in the entire sample set. Here we perform simultaneous amplicon-sequencing-based variant discovery and genotyping for coding exons of 25 GWAS risk genes in 41,911 UK residents of white European origin, comprising 24,892 subjects with six autoimmune disease phenotypes and 17,019 controls, and show that rare coding-region variants at known loci have a negligible role in common autoimmune disease susceptibility. These results do not support the rare-variant synthetic genome-wide-association hypothesis (in which unobserved rare causal variants lead to association detected at common tag variants). Many known autoimmune disease risk loci contain multiple, independently associated, common and low-frequency variants, and so genes at these loci are a priori stronger candidates for harbouring rare coding-region variants than other genes. Our data indicate that the missing heritability for common autoimmune diseases may not be attributable to the rare coding-region variant portion of the allelic spectrum, but perhaps, as others have proposed, may be a result of many common-variant loci of weak effect.

  14. Discovering disease associations by integrating electronic clinical data and medical literature.

    PubMed

    Holmes, Antony B; Hawson, Alexander; Liu, Feng; Friedman, Carol; Khiabanian, Hossein; Rabadan, Raul

    2011-01-01

    Electronic health record (EHR) systems offer an exceptional opportunity for studying many diseases and their associated medical conditions within a population. The increasing number of clinical record entries that have become available electronically provides access to rich, large sets of patients' longitudinal medical information. By integrating and comparing relations found in the EHRs with those already reported in the literature, we are able to verify existing and to identify rare or novel associations. Of particular interest is the identification of rare disease co-morbidities, where the small numbers of diagnosed patients make robust statistical analysis difficult. Here, we introduce ADAMS, an Application for Discovering Disease Associations using Multiple Sources, which contains various statistical and language processing operations. We apply ADAMS to the New York-Presbyterian Hospital's EHR to combine the information from the relational diagnosis tables and textual discharge summaries with those from PubMed and Wikipedia in order to investigate the co-morbidities of the rare diseases Kaposi sarcoma, toxoplasmosis, and Kawasaki disease. In addition to finding well-known characteristics of diseases, ADAMS can identify rare or previously unreported associations. In particular, we report a statistically significant association between Kawasaki disease and diagnosis of autistic disorder.

  15. Discovering Disease Associations by Integrating Electronic Clinical Data and Medical Literature

    PubMed Central

    Holmes, Antony B.; Hawson, Alexander; Liu, Feng; Friedman, Carol; Khiabanian, Hossein; Rabadan, Raul

    2011-01-01

    Electronic health record (EHR) systems offer an exceptional opportunity for studying many diseases and their associated medical conditions within a population. The increasing number of clinical record entries that have become available electronically provides access to rich, large sets of patients' longitudinal medical information. By integrating and comparing relations found in the EHRs with those already reported in the literature, we are able to verify existing and to identify rare or novel associations. Of particular interest is the identification of rare disease co-morbidities, where the small numbers of diagnosed patients make robust statistical analysis difficult. Here, we introduce ADAMS, an Application for Discovering Disease Associations using Multiple Sources, which contains various statistical and language processing operations. We apply ADAMS to the New York-Presbyterian Hospital's EHR to combine the information from the relational diagnosis tables and textual discharge summaries with those from PubMed and Wikipedia in order to investigate the co-morbidities of the rare diseases Kaposi sarcoma, toxoplasmosis, and Kawasaki disease. In addition to finding well-known characteristics of diseases, ADAMS can identify rare or previously unreported associations. In particular, we report a statistically significant association between Kawasaki disease and diagnosis of autistic disorder. PMID:21731656

  16. Rare Earth Oxide Fluoride Nanoparticles And Hydrothermal Method For Forming Nanoparticles

    DOEpatents

    Fulton, John L.; Hoffmann, Markus M.

    2003-12-23

    A hydrothermal method for forming nanoparticles of a rare earth element, oxygen and fluorine has been discovered. Nanoparticles comprising a rare earth element, oxygen and fluorine are also described. These nanoparticles can exhibit excellent refractory properties as well as remarkable stability in hydrothermal conditions. The nanoparticles can exhibit excellent properties for numerous applications including fiber reinforcement of ceramic composites, catalyst supports, and corrosion resistant coatings for high-temperature aqueous solutions.

  17. Rare earth oxide fluoride nanoparticles and hydrothermal method for forming nanoparticles

    DOEpatents

    Fulton, John L [Richland, WA; Hoffmann, Markus M [Richland, WA

    2001-11-13

    A hydrothermal method for forming nanoparticles of a rare earth element, oxygen and fluorine has been discovered. Nanoparticles comprising a rare earth element, oxygen and fluorine are also described. These nanoparticles can exhibit excellent refractory properties as well as remarkable stability in hydrothermal conditions. The nanoparticles can exhibit excellent properties for numerous applications including fiber reinforcement of ceramic composites, catalyst supports, and corrosion resistant coatings for high-temperature aqueous solutions.

  18. A Rare SNP Identified a TCP Transcription Factor Essential for Tendril Development in Cucumber.

    PubMed

    Wang, Shenhao; Yang, Xueyong; Xu, Mengnan; Lin, Xingzhong; Lin, Tao; Qi, Jianjian; Shao, Guangjin; Tian, Nana; Yang, Qing; Zhang, Zhonghua; Huang, Sanwen

    2015-12-07

    Rare genetic variants are abundant in genomes but less tractable in genome-wide association study. Here we exploit a strategy of rare variation mapping to discover a gene essential for tendril development in cucumber (Cucumis sativus L.). In a collection of >3000 lines, we discovered a unique tendril-less line that forms branches instead of tendrils and, therefore, loses its climbing ability. We hypothesized that this unusual phenotype was caused by a rare variation and subsequently identified the causative single nucleotide polymorphism. The affected gene TEN encodes a TCP transcription factor conserved within the cucurbits and is expressed specifically in tendrils, representing a new organ identity gene. The variation occurs within a protein motif unique to the cucurbits and impairs its function as a transcriptional activator. Analyses of transcriptomes from near-isogenic lines identified downstream genes required for the tendril's capability to sense and climb a support. This study provides an example to explore rare functional variants in plant genomes. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  19. A rare case of non-metastatic cholangiocarcinoma in a long standing choledochal cyst

    PubMed Central

    Goukassian, ID; Kussman, SR; Toribo, Y; McAneny, DB; Rosen, JE

    2012-01-01

    Choledochal cysts are rare benign growths that can develop into cancerous lesions if left untreated. The cysts are commonly discovered incidentally during imaging procedures for other reasons. Surgical resection is recommended to avoid risk of cancer or metastatic disease. A rare case of a non-metastatic cholangiocarcinoma in a longstanding choledochal cyst is presented in this case report. PMID:24960829

  20. A rare case of non-metastatic cholangiocarcinoma in a long standing choledochal cyst.

    PubMed

    Goukassian, Id; Kussman, Sr; Toribo, Y; McAneny, Db; Rosen, Je

    2012-04-01

    Choledochal cysts are rare benign growths that can develop into cancerous lesions if left untreated. The cysts are commonly discovered incidentally during imaging procedures for other reasons. Surgical resection is recommended to avoid risk of cancer or metastatic disease. A rare case of a non-metastatic cholangiocarcinoma in a longstanding choledochal cyst is presented in this case report. © JSCR.

  1. How to See a Recently Discovered Supernova

    ScienceCinema

    Nugent, Peter

    2017-12-12

    Berkeley Lab scientist Peter Nugent discusses a recently discovered supernova that is closer to Earth — approximately 21 million light-years away — than any other of its kind in a generation. Astronomers believe they caught the supernova within hours of its explosion, a rare feat made possible with a specialized survey telescope and state-of-the-art computational tools. The finding of such a supernova so early and so close has energized the astronomical community as they are scrambling to observe it with as many telescopes as possible, including the Hubble Space Telescope. More info on how to see it: http://newscenter.lbl.gov/feature-stories/2011/08/31/glimpse-cosmic-explosion/ News release: http://newscenter.lbl.gov/feature-stories/2011/08/25/supernova/

  2. How to See a Recently Discovered Supernova

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

    Nugent, Peter

    2011-08-31

    Berkeley Lab scientist Peter Nugent discusses a recently discovered supernova that is closer to Earth — approximately 21 million light-years away — than any other of its kind in a generation. Astronomers believe they caught the supernova within hours of its explosion, a rare feat made possible with a specialized survey telescope and state-of-the-art computational tools. The finding of such a supernova so early and so close has energized the astronomical community as they are scrambling to observe it with as many telescopes as possible, including the Hubble Space Telescope. More info on how to see it: http://newscenter.lbl.gov/feature-stories/2011/08/31/glimpse-cosmic-explosion/ News release:more » http://newscenter.lbl.gov/feature-stories/2011/08/25/supernova/« less

  3. REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants.

    PubMed

    Ioannidis, Nilah M; Rothstein, Joseph H; Pejaver, Vikas; Middha, Sumit; McDonnell, Shannon K; Baheti, Saurabh; Musolf, Anthony; Li, Qing; Holzinger, Emily; Karyadi, Danielle; Cannon-Albright, Lisa A; Teerlink, Craig C; Stanford, Janet L; Isaacs, William B; Xu, Jianfeng; Cooney, Kathleen A; Lange, Ethan M; Schleutker, Johanna; Carpten, John D; Powell, Isaac J; Cussenot, Olivier; Cancel-Tassin, Geraldine; Giles, Graham G; MacInnis, Robert J; Maier, Christiane; Hsieh, Chih-Lin; Wiklund, Fredrik; Catalona, William J; Foulkes, William D; Mandal, Diptasri; Eeles, Rosalind A; Kote-Jarai, Zsofia; Bustamante, Carlos D; Schaid, Daniel J; Hastie, Trevor; Ostrander, Elaine A; Bailey-Wilson, Joan E; Radivojac, Predrag; Thibodeau, Stephen N; Whittemore, Alice S; Sieh, Weiva

    2016-10-06

    The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery of disease variants from exome sequencing studies. We developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. REVEL was trained with recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. When applied to two independent test sets, REVEL had the best overall performance (p < 10 -12 ) as compared to any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies <0.5%. The area under the receiver operating characteristic curve (AUC) for REVEL was 0.046-0.182 higher in an independent test set of 935 recent SwissVar disease variants and 123,935 putatively neutral exome sequencing variants and 0.027-0.143 higher in an independent test set of 1,953 pathogenic and 2,406 benign variants recently reported in ClinVar than the AUCs for other ensemble methods. We provide pre-computed REVEL scores for all possible human missense variants to facilitate the identification of pathogenic variants in the sea of rare variants discovered as sequencing studies expand in scale. Copyright © 2016 American Society of Human Genetics. All rights reserved.

  4. Primary breast lymphoma: a consideration in an HIV patient when a mass is discovered by screening mammography: a case report.

    PubMed

    Akinwande, Olagoke K; Paley, Robert

    2008-12-11

    Primary Breast lymphoma is a rare lesion that has been reported in patients without HIV. However, Primary Breast lymphoma occurring in a patient with HIV has rarely been reported despite the fact that HIV infection is known to increase the propensity to develop certain types of lymphoma. We report a case of an HIV patient with breast lymphoma that was discovered by screening mammography while presenting our argument for more cautionary management in this patient population.

  5. Whole-exome Sequence Analysis Implicates Rare Il17REL Variants in Familial and Sporadic Inflammatory Bowel Disease.

    PubMed

    Sasaki, Mark M; Skol, Andrew D; Hungate, Eric A; Bao, Riyue; Huang, Lei; Kahn, Stacy A; Allan, James M; Brant, Steven R; McGovern, Dermot P B; Peter, Inga; Silverberg, Mark S; Cho, Judy H; Kirschner, Barbara S; Onel, Kenan

    2016-01-01

    Rare variants (<1%) likely contribute significantly to risk for common diseases such as inflammatory bowel disease (IBD) in specific patient subsets, such as those with high familiality. They are, however, extraordinarily challenging to identify. To discover candidate rare variants associated with IBD, we performed whole-exome sequencing on 6 members of a pediatric-onset IBD family with multiple affected individuals. To determine whether the variants discovered in this family are also associated with nonfamilial IBD, we investigated their influence on disease in 2 large case-control (CC) series. We identified 2 rare variants, rs142430606 and rs200958270, both in the established IBD-susceptibility gene IL17REL, carried by all 4 affected family members and their obligate carrier parents. We then demonstrated that both variants are associated with sporadic ulcerative colitis (UC) in 2 independent data sets. For UC in CC 1: rs142430606 (odds ratio [OR] = 2.99, Padj = 0.028; minor allele frequency [MAF]cases = 0.0063, MAFcontrols = 0.0021); rs200958270 (OR = 2.61, Padj = 0.082; MAFcases = 0.0045, MAFcontrols = 0.0017). For UC in CC 2: rs142430606 (OR = 1.94, P = 0.0056; MAFcases = 0.0071, MAFcontrols = 0.0045); rs200958270 (OR = 2.08, P = 0.0028; MAFcases = 0.0071, MAFcontrols = 0.0042). We discover in a family and replicate in 2 CC data sets 2 rare susceptibility variants for IBD, both in IL17REL. Our results illustrate that whole-exome sequencing performed on disease-enriched families to guide association testing can be an efficient strategy for the discovery of rare disease-associated variants. We speculate that rare variants identified in families and confirmed in the general population may be important modifiers of disease risk for patients with a family history, and that genetic testing of these variants may be warranted in this patient subset.

  6. The discovery of medicines for rare diseases

    PubMed Central

    Swinney, David C; Xia, Shuangluo

    2015-01-01

    There is a pressing need for new medicines (new molecular entities; NMEs) for rare diseases as few of the 6800 rare diseases (according to the NIH) have approved treatments. Drug discovery strategies for the 102 orphan NMEs approved by the US FDA between 1999 and 2012 were analyzed to learn from past success: 46 NMEs were first in class; 51 were followers; and five were imaging agents. First-in-class medicines were discovered with phenotypic assays (15), target-based approaches (12) and biologic strategies (18). Identification of genetic causes in areas with more basic and translational research such as cancer and in-born errors in metabolism contributed to success regardless of discovery strategy. In conclusion, greater knowledge increases the chance of success and empirical solutions can be effective when knowledge is incomplete. PMID:25068983

  7. Thymolipoma combined with hyperthyroidism discovered by neurological symptoms.

    PubMed

    Takahashi, Hidenobu; Harada, Masahiko; Kimura, Masakazu; Kato, Harubumi

    2007-04-01

    Thymolipomas are rare slow-growing mediastinal thymic neoplasms. Most cases are asymptomatic and are sometimes discovered as a huge mass on chest x-ray films. A few cases have been discovered during examinations for other diseases. We report the second case of thymolipoma combined with hyperthyroidism in the English language literature. Neurological symptoms suddenly appeared in a 45-year-old woman. Central nervous system disorder was suggested but no significant abnormalities were found on brain MR nor were there any neurological signs. Several months later, neurological and systemic examinations on admission revealed hyperthyroidism and an anterior mediastinal tumor, 9.0x5.0x3.0 cm in size on chest CT films. Despite treatment of hyperthyroidism by medication, her neurological symptoms remained. Neurologists recommended resection of the mediastinal tumor. Malignancy could not be ruled out because of the irregularity of the tumor appearance on contrast-enhanced chest CT. Furthermore, the tumor appeared to be attached to the ascending aorta, so cytological and/or pathological diagnosis by CT-guided needle biopsy before operation were contraindicated. Extended thymectomy was performed in May 2005. The pathological diagnosis was benign thymolipoma consisting of mature fatty tissue and thymic tissue structures with Hassall's corpuscles. Her neurological symptoms seemed slightly but not markedly improved. The relationship between thymolipoma and hyperthyroidism is still unknown.

  8. Enlarging cystic lymphangioma of the mediastinum in an adult: is this a neoplastic lesion related to the recently discovered PIK3CA mutation?

    PubMed

    Tajima, Shogo; Takanashi, Yusuke; Koda, Kenji

    2015-01-01

    Cystic lymphangioma, a lymphatic system malformation, is usually observed in infants and children and is rarely found in adults. It most commonly occurs in the cervicofacial region, followed by the axilla. Mediastinal cystic lymphangioma is rare, accounting for 1.8% of all mediastinal cysts. Herein, we present an exceedingly rare adult case of mediastinal cystic lymphangioma that had increased in size over a 5-year period. Although fluid collection might be an alternative explanation for this increase in size, this lymphangioma might harbor a neoplastic nature related to the recently discovered PIK3CA mutation.

  9. Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility

    PubMed Central

    Kimura, Hiroki; Tsuboi, Daisuke; Wang, Chenyao; Kushima, Itaru; Koide, Takayoshi; Ikeda, Masashi; Iwayama, Yoshimi; Toyota, Tomoko; Yamamoto, Noriko; Kunimoto, Shohko; Nakamura, Yukako; Yoshimi, Akira; Banno, Masahiro; Xing, Jingrui; Takasaki, Yuto; Yoshida, Mami; Aleksic, Branko; Uno, Yota; Okada, Takashi; Iidaka, Tetsuya; Inada, Toshiya; Suzuki, Michio; Ujike, Hiroshi; Kunugi, Hiroshi; Kato, Tadafumi; Yoshikawa, Takeo; Iwata, Nakao; Kaibuchi, Kozo; Ozaki, Norio

    2015-01-01

    Background: Nuclear distribution E homolog 1 (NDE1), located within chromosome 16p13.11, plays an essential role in microtubule organization, mitosis, and neuronal migration and has been suggested by several studies of rare copy number variants to be a promising schizophrenia (SCZ) candidate gene. Recently, increasing attention has been paid to rare single-nucleotide variants (SNVs) discovered by deep sequencing of candidate genes, because such SNVs may have large effect sizes and their functional analysis may clarify etiopathology. Methods and Results: We conducted mutation screening of NDE1 coding exons using 433 SCZ and 145 pervasive developmental disorders samples in order to identify rare single nucleotide variants with a minor allele frequency ≤5%. We then performed genetic association analysis using a large number of unrelated individuals (3554 SCZ, 1041 bipolar disorder [BD], and 4746 controls). Among the discovered novel rare variants, we detected significant associations between SCZ and S214F (P = .039), and between BD and R234C (P = .032). Furthermore, functional assays showed that S214F affected axonal outgrowth and the interaction between NDE1 and YWHAE (14-3-3 epsilon; a neurodevelopmental regulator). Conclusions: This study strengthens the evidence for association between rare variants within NDE1 and SCZ, and may shed light into the molecular mechanisms underlying this severe psychiatric disorder. PMID:25332407

  10. Towards the automated generation of expert profiles for rare diseases through bibliometric analysis.

    PubMed

    Pflugrad, Andreas; Jurkat-Rott, Karin; Lehmann-Horn, Frank; Bernauer, Jochen

    2014-01-01

    For patients suffering from rare diseases it is often hard to find an expert clinician. Existing registries rely on manual registration procedures and cannot easily be kept up to date. A prototype data collection system for discovering experts on rare diseases using MEDLINE has been successfully deployed. Initial manual analyses demonstrate proof of concept and deliver promising results. Examining the associations between authors, diseases and MeSH-Terms is expected to open up a variety of possibilities beyond expert discovery.

  11. Digimarc Discover on Google Glass

    NASA Astrophysics Data System (ADS)

    Rogers, Eliot; Rodriguez, Tony; Lord, John; Alattar, Adnan

    2015-03-01

    This paper reports on the implementation of the Digimarc® Discover platform on Google Glass, enabling the reading of a watermark embedded in a printed material or audio. The embedded watermark typically contains a unique code that identifies the containing media or object and a synchronization signal that allows the watermark to be read robustly. The Digimarc Discover smartphone application can read the watermark from a small portion of printed image presented at any orientation or reasonable distance. Likewise, Discover can read the recently introduced Digimarc Barcode to identify and manage consumer packaged goods in the retail channel. The Digimarc Barcode has several advantages over the traditional barcode and is expected to save the retail industry millions of dollars when deployed at scale. Discover can also read an audio watermark from ambient audio captured using a microphone. The Digimarc Discover platform has been widely deployed on the iPad, iPhone and many Android-based devices, but it has not yet been implemented on a head-worn wearable device, such as Google Glass. Implementing Discover on Google Glass is a challenging task due to the current hardware and software limitations of the device. This paper identifies the challenges encountered in porting Discover to the Google Glass and reports on the solutions created to deliver a prototype implementation.

  12. Two rare cases of Diphyllobothrium latum parvum type infection in Korea.

    PubMed

    Lee, S H; Chai, J Y; Seo, M; Kook, J; Huh, S; Ryang, Y S; Ahn, Y K

    1994-06-01

    Two rare cases of human infection with parvum (dwarf) type of Diphyllobothrium latum [syn. D. parvum (Stephens, 1908)], were discovered in Korea. The first case was a 46-year old housewife, from whom a kind of pseudophyllidean tapeworm eggs was detected in the feces. She was treated with praziquantel and purged, and a complete strobila with scolex, 120 cm in total length, was recovered. She recalled that she had eaten raw trouts at a raw-fish restaurant near the Chungju Lake. Another patient was a 22-year old medical student (male), who used to eat raw sea-foods. He discovered a chain of tapeworm proglottids, 15 cm in length, discharged spontaneously in his stool and brought it for identification. The worms from the two cases were compatible with D. parvum (Stephens, 1908) of which the taxonomic significance has long been questioned. After a detailed morphological study and review of literature, we designated the worms as D. latum parvum type. This is the first report on the occurrence of this rare type of D. latum infection in Korea.

  13. [A rare cause of anosmia: nasosinusal tuberculosis].

    PubMed

    Hemmaoui, B; Fejjal, N; Errami, N; Temsamani, H; Benchafai, I; Jahidi, A; Benariba, F

    2014-10-01

    We report the case of a 46-year-old-woman who presented with anosmia and nasal obstruction. Primary nasal tuberculosis was discovered. Primary nasal tuberculosis is very rare. Women are more touched than men. Symptomatology is often unilateral with nasal obstruction, anterior rhinorrhea or epistaxis. Diagnosis relies on the anatomopathologic and bacteriological examinations. The treatment is mainly medical based on antituberculosis drugs. In the light of this case report, a review of the literature was made. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Rare Z boson decays to a hidden sector

    DOE PAGES

    Blinov, Nikita; Izaguirre, Eder; Shuve, Brian

    2018-01-18

    We demonstrate that rare decays of the Standard Model Z boson can be used to discover and characterize the nature of new hidden-sector particles. We propose new searches for these particles in soft, high-multiplicity leptonic final states at the Large Hadron Collider. The proposed searches are sensitive to low-mass particles produced in Z decays, and we argue that these striking signatures can shed light on the hidden-sector couplings and mechanism for mass generation.

  15. Rare Z boson decays to a hidden sector

    DOE PAGES

    Blinov, Nikita; Izaguirre, Eder; Shuve, Brian

    2018-01-01

    We demonstrate that rare decays of the Standard Model Z boson can be used to discover and characterize the nature of new hidden-sector particles. We propose new searches for these particles in soft, high-multiplicity leptonic final states at the Large Hadron Collider. The proposed searches are sensitive to low-mass particles produced in Z decays, and we argue that these striking signatures can shed light on the hidden-sector couplings and mechanism for mass generation.

  16. Rare Z boson decays to a hidden sector

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

    Blinov, Nikita; Izaguirre, Eder; Shuve, Brian

    We demonstrate that rare decays of the Standard Model Z boson can be used to discover and characterize the nature of new hidden-sector particles. We propose new searches for these particles in soft, high-multiplicity leptonic final states at the Large Hadron Collider. The proposed searches are sensitive to low-mass particles produced in Z decays, and we argue that these striking signatures can shed light on the hidden-sector couplings and mechanism for mass generation.

  17. Integrated rare variant-based risk gene prioritization in disease case-control sequencing studies.

    PubMed

    Lin, Jhih-Rong; Zhang, Quanwei; Cai, Ying; Morrow, Bernice E; Zhang, Zhengdong D

    2017-12-01

    Rare variants of major effect play an important role in human complex diseases and can be discovered by sequencing-based genome-wide association studies. Here, we introduce an integrated approach that combines the rare variant association test with gene network and phenotype information to identify risk genes implicated by rare variants for human complex diseases. Our data integration method follows a 'discovery-driven' strategy without relying on prior knowledge about the disease and thus maintains the unbiased character of genome-wide association studies. Simulations reveal that our method can outperform a widely-used rare variant association test method by 2 to 3 times. In a case study of a small disease cohort, we uncovered putative risk genes and the corresponding rare variants that may act as genetic modifiers of congenital heart disease in 22q11.2 deletion syndrome patients. These variants were missed by a conventional approach that relied on the rare variant association test alone.

  18. Letting students discover the power, and the limits, of simple models: Coulomb's law

    NASA Astrophysics Data System (ADS)

    Bohacek, Peter; Vonk, Matthew; Dill, Joseph; Boehm, Emma

    2017-09-01

    The inverse-square law pops up all over. It's a simplified model of reality that describes light, sound, gravity, and static electricity. But when it's brought up in class, students are often just handed the equations. They rarely have an opportunity to discover Coulomb's law or Newton's law of gravitation for themselves. It's not hard to understand why. A quantitative demonstration of Coulomb's law can be difficult. The forces are smaller than many force sensors can measure and static electricity tends to be finicky. In addition, off-the-shelf units are expensive or difficult to use. As a result, many instructors skip this lab in favor of qualitative demonstrations or simulations. Adolf Cortel sought to remedy this by designing a straightforward experiment for measuring Coulomb's law using charged metalized-glass spheres (Christmas ornaments) and an electronic balance. Building on Cortel's design, we've made a series of video-based experiments that students can use to discover the relationships that underlie electric force.

  19. HEALER: homomorphic computation of ExAct Logistic rEgRession for secure rare disease variants analysis in GWAS

    PubMed Central

    Wang, Shuang; Zhang, Yuchen; Dai, Wenrui; Lauter, Kristin; Kim, Miran; Tang, Yuzhe; Xiong, Hongkai; Jiang, Xiaoqian

    2016-01-01

    Motivation: Genome-wide association studies (GWAS) have been widely used in discovering the association between genotypes and phenotypes. Human genome data contain valuable but highly sensitive information. Unprotected disclosure of such information might put individual’s privacy at risk. It is important to protect human genome data. Exact logistic regression is a bias-reduction method based on a penalized likelihood to discover rare variants that are associated with disease susceptibility. We propose the HEALER framework to facilitate secure rare variants analysis with a small sample size. Results: We target at the algorithm design aiming at reducing the computational and storage costs to learn a homomorphic exact logistic regression model (i.e. evaluate P-values of coefficients), where the circuit depth is proportional to the logarithmic scale of data size. We evaluate the algorithm performance using rare Kawasaki Disease datasets. Availability and implementation: Download HEALER at http://research.ucsd-dbmi.org/HEALER/ Contact: shw070@ucsd.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26446135

  20. Development of Rare Bacterial Monosaccharide Analogs for Metabolic Glycan Labeling in Pathogenic Bacteria.

    PubMed

    Clark, Emily L; Emmadi, Madhu; Krupp, Katharine L; Podilapu, Ananda R; Helble, Jennifer D; Kulkarni, Suvarn S; Dube, Danielle H

    2016-12-16

    Bacterial glycans contain rare, exclusively bacterial monosaccharides that are frequently linked to pathogenesis and essentially absent from human cells. Therefore, bacterial glycans are intriguing molecular targets. However, systematic discovery of bacterial glycoproteins is hampered by the presence of rare deoxy amino sugars, which are refractory to traditional glycan-binding reagents. Thus, the development of chemical tools that label bacterial glycans is a crucial step toward discovering and targeting these biomolecules. Here, we explore the extent to which metabolic glycan labeling facilitates the studying and targeting of glycoproteins in a range of pathogenic and symbiotic bacterial strains. We began with an azide-containing analog of the naturally abundant monosaccharide N-acetylglucosamine and discovered that it is not broadly incorporated into bacterial glycans, thus revealing a need for additional azidosugar substrates to broaden the utility of metabolic glycan labeling in bacteria. Therefore, we designed and synthesized analogs of the rare deoxy amino d-sugars N-acetylfucosamine, bacillosamine, and 2,4-diacetamido-2,4,6-trideoxygalactose and established that these analogs are differentially incorporated into glycan-containing structures in a range of pathogenic and symbiotic bacterial species. Further application of these analogs will refine our knowledge of the glycan repertoire in diverse bacteria and may find utility in treating a variety of infectious diseases with selectivity.

  1. Computational search for rare-earth free hard-magnetic materials

    NASA Astrophysics Data System (ADS)

    Flores Livas, José A.; Sharma, Sangeeta; Dewhurst, John Kay; Gross, Eberhard; MagMat Team

    2015-03-01

    It is difficult to over state the importance of hard magnets for human life in modern times; they enter every walk of our life from medical equipments (NMR) to transport (trains, planes, cars, etc) to electronic appliances (for house hold use to computers). All the known hard magnets in use today contain rare-earth elements, extraction of which is expensive and environmentally harmful. Rare-earths are also instrumental in tipping the balance of world economy as most of them are mined in limited specific parts of the world. Hence it would be ideal to have similar characteristics as a hard magnet but without or at least with reduced amount of rare-earths. This is the main goal of our work: search for rare-earth-free magnets. To do so we employ a combination of density functional theory and crystal prediction methods. The quantities which define a hard magnet are magnetic anisotropy energy (MAE) and saturation magnetization (Ms), which are the quantities we maximize in search for an ideal magnet. In my talk I will present details of the computation search algorithm together with some potential newly discovered rare-earth free hard magnet. J.A.F.L. acknowledge financial support from EU's 7th Framework Marie-Curie scholarship program within the ``ExMaMa'' Project (329386).

  2. Discover Earth

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Discover Earth is a NASA-funded project for teachers of grades 5-12 who want to expand their knowledge of the Earth system, and prepare to become master teachers who promote Earth system science in their own schools, counties, and throughout their state. Participants from the following states are invited to apply: Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, and Washington, DC. Teachers selected for the project participate in a two-week summer workshop conducted at the University of Maryland, College Park; develop classroom-ready materials during the workshop for broad dissemination; conduct a minimum of two peer training activities during the coming school year; and participate in other enrichment/education opportunities as available and desired. Discover Earth is a team effort that utilizes expertise from a range of contributors, and balances science content with hands-on classroom applications.

  3. Utilising family-based designs for detecting rare variant disease associations.

    PubMed

    Preston, Mark D; Dudbridge, Frank

    2014-03-01

    Rare genetic variants are thought to be important components in the causality of many diseases but discovering these associations is challenging. We demonstrate how best to use family-based designs to improve the power to detect rare variant disease associations. We show that using genetic data from enriched families (those pedigrees with greater than one affected member) increases the power and sensitivity of existing case-control rare variant tests. However, we show that transmission- (or within-family-) based tests do not benefit from this enrichment. This means that, in studies where a limited amount of genotyping is available, choosing a single case from each of many pedigrees has greater power than selecting multiple cases from fewer pedigrees. Finally, we show how a pseudo-case-control design allows a greater range of statistical tests to be applied to family data. © 2014 The Authors. Annals of Human Genetics published by John Wiley & Sons Ltd/University College London.

  4. High-throughput discovery of rare human nucleotide polymorphisms by Ecotilling

    PubMed Central

    Till, Bradley J.; Zerr, Troy; Bowers, Elisabeth; Greene, Elizabeth A.; Comai, Luca; Henikoff, Steven

    2006-01-01

    Human individuals differ from one another at only ∼0.1% of nucleotide positions, but these single nucleotide differences account for most heritable phenotypic variation. Large-scale efforts to discover and genotype human variation have been limited to common polymorphisms. However, these efforts overlook rare nucleotide changes that may contribute to phenotypic diversity and genetic disorders, including cancer. Thus, there is an increasing need for high-throughput methods to robustly detect rare nucleotide differences. Toward this end, we have adapted the mismatch discovery method known as Ecotilling for the discovery of human single nucleotide polymorphisms. To increase throughput and reduce costs, we developed a universal primer strategy and implemented algorithms for automated band detection. Ecotilling was validated by screening 90 human DNA samples for nucleotide changes in 5 gene targets and by comparing results to public resequencing data. To increase throughput for discovery of rare alleles, we pooled samples 8-fold and found Ecotilling to be efficient relative to resequencing, with a false negative rate of 5% and a false discovery rate of 4%. We identified 28 new rare alleles, including some that are predicted to damage protein function. The detection of rare damaging mutations has implications for models of human disease. PMID:16893952

  5. EPR investigation of electronic excitations in rare gas solids (Review Article)

    NASA Astrophysics Data System (ADS)

    Zhitnikov, R. A.; Dmitriev, Yu. A.

    1998-10-01

    The methods are described for producing unstable paramagnetic excited states in rare gas cryocrystals Ne, Ar, Kr, and Xe through the trapping, in the cryocrystals growing from the gas phase, the products of the gas discharge taking place in the same or other rare gas. The paper presents a technique and results of an observation and investigation of excited states in rare gas cryocrystals with electron paramagnetic resonance (EPR). The discovered unstable paramagnetic centers are interpreted as being local metastable excited np5(n+1)s atomic-type states in rare gas cryocrystals which are subject to the action of the anisotropic electric field resulted from the crystal surroundings distorted by the center. An account is given of the mechanisms for formation of observed paramagnetic excited states in cryocrystals which arise owing to the excitation energy of the metastable 3P2 atoms of Ne, Ar, Kr, Xe and He 23S1 and 21S0 atoms that form in the discharge in an appropriate gas and trap in the growing cryocrystal.

  6. What can we learn about lipoprotein metabolism and coronary heart disease from studying rare variants?

    PubMed

    Jeff, Janina M; Peloso, Gina M; Do, Ron

    2016-04-01

    Rare variant association studies (RVAS) target the class of genetic variation with frequencies less than 1%. Recently, investigators have used exome sequencing in RVAS to identify rare alleles responsible for Mendelian diseases but have experienced greater difficulty discovering such alleles for complex diseases. In this review, we describe what we have learned about lipoprotein metabolism and coronary heart disease through the conduct of RVAS. Rare protein-altering genetic variation can provide important insights that are not as easily attainable from common variant association studies. First, RVAS can facilitate gene discovery by identifying novel rare protein-altering variants in specific genes that are associated with disease. Second, rare variant associations can provide supportive evidence for putative drug targets for novel therapies. Finally, rare variants can uncover new pathways and reveal new biologic mechanisms. The field of human genetics has already made tremendous progress in understanding lipoprotein metabolism and the causes of coronary heart disease in the context of rare variants. As next generation sequencing becomes more cost-effective, RVAS with larger sample sizes will be conducted. This will lead to more novel rare variant discoveries and the translation of genomic data into biological knowledge and clinical insights for cardiovascular disease.

  7. Rare events in finite and infinite dimensions

    NASA Astrophysics Data System (ADS)

    Reznikoff, Maria G.

    Thermal noise introduces stochasticity into deterministic equations and makes possible events which are never seen in the zero temperature setting. The driving force behind the thesis work is a desire to bring analysis and probability to bear on a class of relevant and intriguing physical problems, and in so doing, to allow applications to drive the development of new mathematical theory. The unifying theme is the study of rare events under the influence of small, random perturbations, and the manifold mathematical problems which ensue. In the first part, we apply large deviation theory and prefactor estimates to a coherent rotation micromagnetic model in order to analyze thermally activated magnetic switching. We consider recent physical experiments and the mathematical questions "asked" by them. A stochastic resonance type phenomenon is discovered, leading to the definition of finite temperature astroids. Non-Arrhenius behavior is discussed. The analysis is extended to ramped astroids. In addition, we discover that for low damping and ultrashort pulses, deterministic effects can override thermal effects, in accord with very recent ultrashort pulse experiments. Even more interesting, perhaps, is the study of large deviations in the infinite dimensional context, i.e. in spatially extended systems. Inspired by recent numerical investigations, we study the stochastically perturbed Allen Cahn and Cahn Hilliard equations. For the Allen Cahn equation, we study the action minimization problem (a deterministic variational problem) and prove the action scaling in four parameter regimes, via upper and lower bounds. The sharp interface limit is studied. We formally derive a reduced action functional which lends insight into the connection between action minimization and curvature flow. For the Cahn Hilliard equation, we prove upper and lower bounds for the scaling of the energy barrier in the nucleation and growth regime. Finally, we consider rare events in large or infinite

  8. DISCOVER-AQ Aircraft insitu TraceGas Data (ICT)

    Atmospheric Science Data Center

    2018-03-28

    DISCOVER-AQ Aircraft insitu TraceGas Data (ICT) Project Title:  N/A Platform:  NASA ... Relevant Documents:  DISCOVER-AQ - Airborne Science Data for Atmospheric Composition DISCOVER-AQ - NASA Earth ...

  9. Systematic Serendipity: A Method to Discover the Anomalous

    NASA Astrophysics Data System (ADS)

    Giles, Daniel; Walkowicz, Lucianne

    2018-01-01

    One of the challenges in the era of big data astronomical surveys is identifying anomalous data, data that exhibits as-of-yet unobserved behavior. These data may result from systematic errors, extreme (or rare) forms of known phenomena, or, most interestingly, truly novel phenomena that has historically required a trained eye and often fortuitous circumstance to identify. We describe a method that uses machine clustering techniques to discover anomalous data in Kepler lightcurves, as a step towards systematizing the detection of novel phenomena in the era of LSST. As a proof of concept, we apply our anomaly detection method to Kepler data including Boyajian's Star (KIC 8462852). We examine quarters 4, 8, 11, and 16 of the Kepler data which contain Boyajian’s Star acting normally (quarters 4 and 11) and anomalously (quarters 8 and 16). We demonstrate that our method is capable of identifying Boyajian’s Star’s anomalous behavior in quarters of interest, and we further identify other anomalous light curves that exhibit a range of interesting variability.

  10. Discovery of rare, diagnostic AluYb8/9 elements in diverse human populations.

    PubMed

    Feusier, Julie; Witherspoon, David J; Scott Watkins, W; Goubert, Clément; Sasani, Thomas A; Jorde, Lynn B

    2017-01-01

    Polymorphic human Alu elements are excellent tools for assessing population structure, and new retrotransposition events can contribute to disease. Next-generation sequencing has greatly increased the potential to discover Alu elements in human populations, and various sequencing and bioinformatics methods have been designed to tackle the problem of detecting these highly repetitive elements. However, current techniques for Alu discovery may miss rare, polymorphic Alu elements. Combining multiple discovery approaches may provide a better profile of the polymorphic Alu mobilome. Alu Yb8/9 elements have been a focus of our recent studies as they are young subfamilies (~2.3 million years old) that contribute ~30% of recent polymorphic Alu retrotransposition events. Here, we update our ME-Scan methods for detecting Alu elements and apply these methods to discover new insertions in a large set of individuals with diverse ancestral backgrounds. We identified 5,288 putative Alu insertion events, including several hundred novel Alu Yb8/9 elements from 213 individuals from 18 diverse human populations. Hundreds of these loci were specific to continental populations, and 23 non-reference population-specific loci were validated by PCR. We provide high-quality sequence information for 68 rare Alu Yb8/9 elements, of which 11 have hallmarks of an active source element. Our subfamily distribution of rare Alu Yb8/9 elements is consistent with previous datasets, and may be representative of rare loci. We also find that while ME-Scan and low-coverage, whole-genome sequencing (WGS) detect different Alu elements in 41 1000 Genomes individuals, the two methods yield similar population structure results. Current in-silico methods for Alu discovery may miss rare, polymorphic Alu elements. Therefore, using multiple techniques can provide a more accurate profile of Alu elements in individuals and populations. We improved our false-negative rate as an indicator of sample quality for future

  11. A rare presentation of hepatocellular carcinoma in non-cirrhotic liver.

    PubMed

    Kabbage, Lamia; El Kouhen, Meryem; Taghy, Ahmed; Znati, Kaoutar; Kabbaj, Nawal

    2017-01-01

    Hepatocellular carcinoma is the most frequent type of liver malignancy. Most cases of hepatocellular carcinoma are secondary to either viral hepatitis (hepatitis B, C) or alcoholic cirrhosis. Liver cirrhosis due to any other causes is considered as a risk factor for development of hepatocellular carcinoma; however, hepatocellular carcinoma in non cirrhotic livers remains a rare condition. The present case report describes a 59-year-old woman patient admitted to explore right hypochondriac and epigastric pain, with no evidence of pre-existing liver disease and with a good general condition. The computed tomography was very suggestive of a gastro-intestinal stromal tumor. But, at laparotomy, a huge hepatic tumor was discovered. Histopathological study confirmed the presence of primary hepatocellular carcinoma. Hepatocellular carcinoma occurs more frequently on a cirrhotic liver. However, it can occur on a non cirrhotic liver and remains and extremely rare case.

  12. Did the ancient egyptians discover Algol?

    NASA Astrophysics Data System (ADS)

    Jetsu, L.; Porceddu, S.; Porceddu, S.; Lyytinen, J.; Kajatkari, P.; Markkanen, T.; Toivari-Viitala, J.

    2013-02-01

    Fabritius discovered the first variable star, Mira, in 1596. Holwarda determined the 11 months period of Mira in 1638. Montanari discovered the next variable star, Algol, in 1669. Its period, 2.867 days, was determined by Goodricke (178). Algol was associated with demon-like creatures, "Gorgon" in ancient Greek and "ghoul" in ancient Arab mythology. This indicates that its variability was discovered much before 1669 (Wilk 1996), but this mythological evidence is ambiguous (Davis 1975). For thousands of years, the Ancient Egyptian Scribes (AES) observed stars for timekeeping in a region, where there are nearly 300 clear nights a year. We discovered a significant periodicity of 2.850 days in their calendar for lucky and unlucky days dated to 1224 BC, "the Cairo Calendar". Several astrophysical and astronomical tests supported our conclusion that this was the period of Algol three millennia ago. The "ghoulish habits" of Algol could explain this 0.017 days period increase (Battersby 2012).

  13. Conditionally Rare Taxa Disproportionately Contribute to Temporal Changes in Microbial Diversity

    DOE PAGES

    Shade, Ashley; Jones, Stuart E.; Caporaso, J. Gregory; ...

    2014-07-15

    Microbial communities typically contain many rare taxa that make up the majority of the observed membership, yet the contribution of this microbial “rare biosphere” to community dynamics is unclear. Using 16S rRNA amplicon sequencing of 3,237 samples from 42 time series of microbial communities from nine different ecosystems (air; marine; lake; stream; adult human skin, tongue, and gut; infant gut; and brewery wastewater treatment), we introduce a new method to detect typically rare microbial taxa that occasionally become very abundant (conditionally rare taxa [CRT]) and then quantify their contributions to temporal shifts in community structure. We discovered that CRT mademore » up 1.5 to 28% of the community membership, represented a broad diversity of bacterial and archaeal lineages, and explained large amounts of temporal community dissimilarity (i.e., up to 97% of Bray-Curtis dissimilarity). Most of the CRT were detected at multiple time points, though we also identified “one-hit wonder” CRT that were observed at only one time point. Using a case study from a temperate lake, we gained additional insights into the ecology of CRT by comparing routine community time series to large disturbance events. Our results reveal that many rare taxa contribute a greater amount to microbial community dynamics than is apparent from their low proportional abundances. In conclusion, this observation was true across a wide range of ecosystems, indicating that these rare taxa are essential for understanding community changes over time.« less

  14. Discovering the Solar System

    NASA Astrophysics Data System (ADS)

    Jones, Barrie W.

    1999-04-01

    Discovering the Solar System Barrie W. Jones The Open University, Milton Keynes, UK Discovering the Solar System is a comprehensive, up-to-date account of the Solar System and of the ways in which the various bodies have been investigated and modelled. The approach is thematic, with sequences of chapters on the interiors of planetary bodies, on their surfaces, and on their atmospheres. Within each sequence there is a chapter on general principles and processes followed by one or two chapters on specific bodies. There is also an introductory chapter, a chapter on the origin of the Solar System, and a chapter on asteroids, comets and meteorites. Liberally illustrated with diagrams, black and white photographs and colour plates, Discovering the Solar System also features: * tables of essential data * question and answers within the text * end of section review questions with answers and comments Discovering the Solar System is essential reading for all undergraduate students for whom astronomy or planetary science are components of their degrees, and for those at a more advanced level approaching the subject for the first time. It will also be of great interest to non-specialists with a keen interest in astronomy. A small amount of scientific knowledge is assumed plus familiarity with basic algebra and graphs. There is no calculus. Praise for this book includes: ".certainly qualifies as an authoritative text. The author clearly has an encyclopedic knowledge of the subject." Meteorics and Planetary Science ".liberally doused with relevant graphs, tables, and black and white figures of good quality." EOS, Transactions of the American Geophysical Union ".one of the best books on the Solar System I have seen. The general accuracy and quality of the content is excellent." Journal of the British Astronomical Association

  15. Discovering Mendeleev's Model.

    ERIC Educational Resources Information Center

    Sterling, Donna

    1996-01-01

    Presents an activity that introduces the historical developments in science that led to the discovery of the periodic table and lets students experience scientific discovery firsthand. Enables students to learn about patterns among the elements and experience how scientists analyze data to discover patterns and build models. (JRH)

  16. BETASEQ: a powerful novel method to control type-I error inflation in partially sequenced data for rare variant association testing.

    PubMed

    Yan, Song; Li, Yun

    2014-02-15

    Despite its great capability to detect rare variant associations, next-generation sequencing is still prohibitively expensive when applied to large samples. In case-control studies, it is thus appealing to sequence only a subset of cases to discover variants and genotype the identified variants in controls and the remaining cases under the reasonable assumption that causal variants are usually enriched among cases. However, this approach leads to inflated type-I error if analyzed naively for rare variant association. Several methods have been proposed in recent literature to control type-I error at the cost of either excluding some sequenced cases or correcting the genotypes of discovered rare variants. All of these approaches thus suffer from certain extent of information loss and thus are underpowered. We propose a novel method (BETASEQ), which corrects inflation of type-I error by supplementing pseudo-variants while keeps the original sequence and genotype data intact. Extensive simulations and real data analysis demonstrate that, in most practical situations, BETASEQ leads to higher testing powers than existing approaches with guaranteed (controlled or conservative) type-I error. BETASEQ and associated R files, including documentation, examples, are available at http://www.unc.edu/~yunmli/betaseq

  17. Asymptomatic tracheal MALT lymphoma discovered on spirometric findings presenting with elevated respiratory resistance.

    PubMed

    Kadota, Naoki; Shinohara, Tsutomu; Machida, Hisanori; Nakanishi, Hirofumi; Suehiro, Fumie; Toda, Hiroko; Yoshino, Tadashi; Ogushi, Fumitaka

    2015-06-06

    Central airway obstruction (CAO) may be caused by various etiologies. However, conventional chest X-rays are rarely diagnostic for patients with CAO. We here described a 64-year-old asymptomatic female with tracheal mucosa-associated lymphoid tissue lymphoma discovered on spirometric findings during a complete physical examination. The plateau of forced expiratory flow was consistent with CAO. A decreased peak expiratory flow rate was noted at least 3 years before the diagnosis, and was attributed to an insufficient effort by the patient. Impulse oscillometric measurements, which were taken during quiet breathing and were effort-independent, suggested elevated respiratory resistance. These abnormalities completely disappeared after radiation therapy. The addition of impulse oscillometry to spirometry may be useful for screening CAO in routine health examinations.

  18. Mangrove rare actinobacteria: taxonomy, natural compound, and discovery of bioactivity

    PubMed Central

    Azman, Adzzie-Shazleen; Othman, Iekhsan; Velu, Saraswati S.; Chan, Kok-Gan; Lee, Learn-Han

    2015-01-01

    Actinobacteria are one of the most important and efficient groups of natural metabolite producers. The genus Streptomyces have been recognized as prolific producers of useful natural compounds as they produced more than half of the naturally-occurring antibiotics isolated to-date and continue as the primary source of new bioactive compounds. Lately, Streptomyces groups isolated from different environments produced the same types of compound, possibly due to frequent genetic exchanges between species. As a result, there is a dramatic increase in demand to look for new compounds which have pharmacological properties from another group of Actinobacteria, known as rare actinobacteria; which is isolated from special environments such as mangrove. Recently, mangrove ecosystem is becoming a hot spot for studies of bioactivities and the discovery of natural products. Many novel compounds discovered from the novel rare actinobacteria have been proven as potential new drugs in medical and pharmaceutical industries such as antibiotics, antimicrobials, antibacterials, anticancer, and antifungals. This review article highlights the latest studies on the discovery of natural compounds from the novel mangrove rare actinobacteria and provides insight on the impact of these findings. PMID:26347734

  19. Mangrove rare actinobacteria: taxonomy, natural compound, and discovery of bioactivity.

    PubMed

    Azman, Adzzie-Shazleen; Othman, Iekhsan; Velu, Saraswati S; Chan, Kok-Gan; Lee, Learn-Han

    2015-01-01

    Actinobacteria are one of the most important and efficient groups of natural metabolite producers. The genus Streptomyces have been recognized as prolific producers of useful natural compounds as they produced more than half of the naturally-occurring antibiotics isolated to-date and continue as the primary source of new bioactive compounds. Lately, Streptomyces groups isolated from different environments produced the same types of compound, possibly due to frequent genetic exchanges between species. As a result, there is a dramatic increase in demand to look for new compounds which have pharmacological properties from another group of Actinobacteria, known as rare actinobacteria; which is isolated from special environments such as mangrove. Recently, mangrove ecosystem is becoming a hot spot for studies of bioactivities and the discovery of natural products. Many novel compounds discovered from the novel rare actinobacteria have been proven as potential new drugs in medical and pharmaceutical industries such as antibiotics, antimicrobials, antibacterials, anticancer, and antifungals. This review article highlights the latest studies on the discovery of natural compounds from the novel mangrove rare actinobacteria and provides insight on the impact of these findings.

  20. Report of a rare case and review of adult intestinal duplication at the opposite side of mesenteric margin.

    PubMed

    Huang, Zhi-Hao; Wan, Zi-Hao; Vikash, Vikash; Vikash, Sindhu; Jiang, Cong-Qing

    2018-01-01

    To study the previously discovered clinical entity of adult intestinal duplication and its treatment, and propose an extension to its existing classification. We report the case of an adult male with abdominal pain, constipation and vomiting. This patient underwent surgical separation of adhesions, reduction of torsion and intestinal decompression. Postoperative pathological findings confirmed the rare diagnosis of intestinal duplication. Adult intestinal duplication is quite rare. Its clinical manifestations are nonspecific. From this finding of intestinal duplication originating at the opposite side of the mesenteric margin, a further extension of the existing anatomical classification is proposed.

  1. Searching for missing heritability: Designing rare variant association studies

    PubMed Central

    Zuk, Or; Schaffner, Stephen F.; Samocha, Kaitlin; Do, Ron; Hechter, Eliana; Kathiresan, Sekar; Daly, Mark J.; Neale, Benjamin M.; Sunyaev, Shamil R.; Lander, Eric S.

    2014-01-01

    Genetic studies have revealed thousands of loci predisposing to hundreds of human diseases and traits, revealing important biological pathways and defining novel therapeutic hypotheses. However, the genes discovered to date typically explain less than half of the apparent heritability. Because efforts have largely focused on common genetic variants, one hypothesis is that much of the missing heritability is due to rare genetic variants. Studies of common variants are typically referred to as genomewide association studies, whereas studies of rare variants are often simply called sequencing studies. Because they are actually closely related, we use the terms common variant association study (CVAS) and rare variant association study (RVAS). In this paper, we outline the similarities and differences between RVAS and CVAS and describe a conceptual framework for the design of RVAS. We apply the framework to address key questions about the sample sizes needed to detect association, the relative merits of testing disruptive alleles vs. missense alleles, frequency thresholds for filtering alleles, the value of predictors of the functional impact of missense alleles, the potential utility of isolated populations, the value of gene-set analysis, and the utility of de novo mutations. The optimal design depends critically on the selection coefficient against deleterious alleles and thus varies across genes. The analysis shows that common variant and rare variant studies require similarly large sample collections. In particular, a well-powered RVAS should involve discovery sets with at least 25,000 cases, together with a substantial replication set. PMID:24443550

  2. Melorheostosis – Case Report of Rare Disease

    PubMed Central

    Kumar, Rakesh; Sankhala, S.S.; Bijarnia, Isha

    2014-01-01

    Introduction: Melorheostosis(synonyms: candle bone disease, melting wax syndrome, Leri disease) is a rare chronic bone disorder, first described in 1922 by Leri and Joanny. Men and women are equally affected, and no hereditary features have been discovered. Onset is insidious, and most common symptom is pain. Most common part of bone is diaphysis of the long bone of lower limb rarely the axial skeleton. Classical radiological appearance of ’flowing hyperosteosis’ resembling hardened wax that has dripped down the side of a candle. Case Report: A 35 years old woman presented with left leg pain with mild swelling and limitation of knee movement. On examination non tender bony heard swelling, hyperpigmented and restriction of knee movement present. Plain radiographs showed extensive, dense, undulating or irregular cortical hyperostosis, resembling candle wax, extending along the length of bone. Pamidronate as well asanalgesic were given to the patient. Physiotherepy started for the deformity. Conclusion: Routine laboratory findings usually are normal. The exact cause remain unclear. There is no definite treatment available for this disease. Only symptomatic treatment improve the condition of the patients, more fruitful result obtain with pamidronate and physiotherapy. PMID:27298954

  3. Demographic history and rare allele sharing among human populations.

    PubMed

    Gravel, Simon; Henn, Brenna M; Gutenkunst, Ryan N; Indap, Amit R; Marth, Gabor T; Clark, Andrew G; Yu, Fuli; Gibbs, Richard A; Bustamante, Carlos D

    2011-07-19

    High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2-4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence.

  4. Demographic history and rare allele sharing among human populations

    PubMed Central

    Gravel, Simon; Henn, Brenna M.; Gutenkunst, Ryan N.; Indap, Amit R.; Marth, Gabor T.; Clark, Andrew G.; Yu, Fuli; Gibbs, Richard A.; Bustamante, Carlos D.; Altshuler, David L.; Durbin, Richard M.; Abecasis, Gonçalo R.; Bentley, David R.; Chakravarti, Aravinda; Clark, Andrew G.; Collins, Francis S.; De La Vega, Francisco M.; Donnelly, Peter; Egholm, Michael; Flicek, Paul; Gabriel, Stacey B.; Gibbs, Richard A.; Knoppers, Bartha M.; Lander, Eric S.; Lehrach, Hans; Mardis, Elaine R.; McVean, Gil A.; Nickerson, Debbie A.; Peltonen, Leena; Schafer, Alan J.; Sherry, Stephen T.; Wang, Jun; Wilson, Richard K.; Gibbs, Richard A.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Wheeler, David; Wang, Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Lander, Eric S.; Altshuler, David L.; Ambrogio, Lauren; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Bentley, David R.; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; McKernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Sudbrak, Ralf; Lehrach, Hans; Borodina, Tatiana A.; Dahl, Andreas; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Rosenstiel, Philip; Schreiber, Stefan; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Egholm, Michael; Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Mardis, Elaine R.; Wilson, Richard K.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; Durbin, Richard M.; Burton, John; Carter, David M.; Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Quail, Michael; Skelly, Tom; Stalker, James; Swerdlow, Harold P.; Turner, Daniel; De Witte, Anniek; Giles, Shane; Gibbs, Richard A.; Wheeler, David; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Wang, Jun; Fang, Xiaodong; Guo, Xiaosen; Li, Ruiqiang; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Li, Guoqing; Wang, Jian; Yang, Huanming; Marth, Gabor T.; Garrison, Erik P.; Huang, Weichun; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Daly, Mark J.; DePristo, Mark A.; Altshuler, David L.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Browning, Brian L.; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Grossman, Sharon R.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Price, Alkes; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Shefler, Erica; Shlyakhter, Ilya A.; Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Bustamante, Carlos D.; Clark, Andrew G.; Boyko, Adam; Degenhardt, Jeremiah; Gravel, Simon; Gutenkunst, Ryan N.; Kaganovich, Mark; Keinan, Alon; Lacroute, Phil; Ma, Xin; Reynolds, Andy; Clarke, Laura; Flicek, Paul; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, William M.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Stütz, Adrian M.; Humphray, Sean; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott; Murray, Lisa; Chakravarti, Aravinda; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Hyland, Fiona C. L.; Manning, Jonathan M.; McLaughlin, Stephen F.; Peckham, Heather E.; Sakarya, Onur; Sun, Yongming A.; Tsung, Eric F.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Sudbrak, Ralf; Albrecht, Marcus W.; Amstislavskiy, Vyacheslav S.; Herwig, Ralf; Parkhomchuk, Dimitri V.; Sherry, Stephen T.; Agarwala, Richa; Khouri, Hoda M.; Morgulis, Aleksandr O.; Paschall, Justin E.; Phan, Lon D.; Rotmistrovsky, Kirill E.; Sanders, Robert D.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Auton, Adam; Iqbal, Zamin; Lunter, Gerton; Marchini, Jonathan L.; Moutsianas, Loukas; Myers, Simon; Tumian, Afidalina; Desany, Brian; Knight, James; Winer, Roger; Craig, David W.; Beckstrom-Sternberg, Steve M.; Christoforides, Alexis; Kurdoglu, Ahmet A.; Pearson, John V.; Sinari, Shripad A.; Tembe, Waibhav D.; Haussler, David; Hinrichs, Angie S.; Katzman, Sol J.; Kern, Andrew; Kuhn, Robert M.; Przeworski, Molly; Hernandez, Ryan D.; Howie, Bryan; Kelley, Joanna L.; Melton, S. Cord; Abecasis, Gonçalo R.; Li, Yun; Anderson, Paul; Blackwell, Tom; Chen, Wei; Cookson, William O.; Ding, Jun; Kang, Hyun Min; Lathrop, Mark; Liang, Liming; Moffatt, Miriam F.; Scheet, Paul; Sidore, Carlo; Snyder, Matthew; Zhan, Xiaowei; Zöllner, Sebastian; Awadalla, Philip; Casals, Ferran; Idaghdour, Youssef; Keebler, John; Stone, Eric A.; Zilversmit, Martine; Jorde, Lynn; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Sahinalp, S. Cenk; Sudmant, Peter H.; Mardis, Elaine R.; Chen, Ken; Chinwalla, Asif; Ding, Li; Koboldt, Daniel C.; McLellan, Mike D.; Dooling, David; Weinstock, George; Wallis, John W.; Wendl, Michael C.; Zhang, Qunyuan; Durbin, Richard M.; Albers, Cornelis A.; Ayub, Qasim; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Carter, David M.; Chen, Yuan; Conrad, Donald F.; Danecek, Petr; Dermitzakis, Emmanouil T.; Hu, Min; Huang, Ni; Hurles, Matt E.; Jin, Hanjun; Jostins, Luke; Keane, Thomas M.; Le, Si Quang; Lindsay, Sarah; Long, Quan; MacArthur, Daniel G.; Montgomery, Stephen B.; Parts, Leopold; Stalker, James; Tyler-Smith, Chris; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Balasubramanian, Suganthi; Bjornson, Robert; Du, Jiang; Grubert, Fabian; Habegger, Lukas; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Li, Yingrui; Luo, Ruibang; Marth, Gabor T.; Garrison, Erik P.; Kural, Deniz; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; McCarroll, Steven A.; Banks, Eric; DePristo, Mark A.; Handsaker, Robert E.; Hartl, Chris; Korn, Joshua M.; Li, Heng; Nemesh, James C.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Degenhardt, Jeremiah; Kaganovich, Mark; Clarke, Laura; Smith, Richard E.; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Humphray, Sean; Cheetham, R. Keira; Eberle, Michael; Kahn, Scott; Murray, Lisa; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Peckham, Heather E.; Sun, Yongming A.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Xiao, Chunlin; Iqbal, Zamin; Desany, Brian; Blackwell, Tom; Snyder, Matthew; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Chen, Ken; Chinwalla, Asif; Ding, Li; McLellan, Mike D.; Wallis, John W.; Hurles, Matt E.; Conrad, Donald F.; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Du, Jiang; Grubert, Fabian; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Gibbs, Richard A.; Bainbridge, Matthew; Challis, Danny; Coafra, Cristian; Dinh, Huyen; Kovar, Christie; Lee, Sandy; Muzny, Donna; Nazareth, Lynne; Reid, Jeff; Sabo, Aniko; Yu, Fuli; Yu, Jin; Marth, Gabor T.; Garrison, Erik P.; Indap, Amit; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Ward, Alistair N.; Wu, Jiantao; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Garimella, Kiran V.; Hartl, Chris; Shefler, Erica; Sougnez, Carrie L.; Wilkinson, Jane; Clark, Andrew G.; Gravel, Simon; Grubert, Fabian; Clarke, Laura; Flicek, Paul; Smith, Richard E.; Zheng-Bradley, Xiangqun; Sherry, Stephen T.; Khouri, Hoda M.; Paschall, Justin E.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Katzman, Sol J.; Abecasis, Gonçalo R.; Blackwell, Tom; Mardis, Elaine R.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Koboldt, Daniel C.; Durbin, Richard M.; Balasubramaniam, Senduran; Coffey, Allison; Keane, Thomas M.; MacArthur, Daniel G.; Palotie, Aarno; Scott, Carol; Stalker, James; Tyler-Smith, Chris; Gerstein, Mark B.; Balasubramanian, Suganthi; Chakravarti, Aravinda; Knoppers, Bartha M.; Abecasis, Gonçalo R.; Bustamante, Carlos D.; Gharani, Neda; Gibbs, Richard A.; Jorde, Lynn; Kaye, Jane S.; Kent, Alastair; Li, Taosha; McGuire, Amy L.; McVean, Gil A.; Ossorio, Pilar N.; Rotimi, Charles N.; Su, Yeyang; Toji, Lorraine H.; TylerSmith, Chris; Brooks, Lisa D.; Felsenfeld, Adam L.; McEwen, Jean E.; Abdallah, Assya; Juenger, Christopher R.; Clemm, Nicholas C.; Collins, Francis S.; Duncanson, Audrey; Green, Eric D.; Guyer, Mark S.; Peterson, Jane L.; Schafer, Alan J.; Abecasis, Gonçalo R.; Altshuler, David L.; Auton, Adam; Brooks, Lisa D.; Durbin, Richard M.; Gibbs, Richard A.; Hurles, Matt E.; McVean, Gil A.

    2011-01-01

    High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence. PMID:21730125

  5. Dive and discover: Expeditions to the seafloor

    NASA Astrophysics Data System (ADS)

    Lawrence, Lisa Ayers

    The Dive and Discover Web site is a virtual treasure chest of deep sea science and classroom resources. The goals of Dive and Discover are to engage students, teachers, and the general public in the excitement of ocean disco very through an interactive educational Web site. You can follow scientists on oceanographic research cruises by reading their daily cruise logs, viewing photos and video clips of the discoveries, and even e-mailing questions to the scientists and crew. WHOI has also included an “Educator's Companion” section with teaching strategies, activities, and assessments, making Dive and Discover an excellent resource for the classroom.

  6. Dive and discover: Expeditions to the seafloor

    NASA Astrophysics Data System (ADS)

    Ayers Lawrence, Lisa

    The Dive and Discover Web site is a virtual treasure chest of deep sea science and classroom resources. The goals of Dive and Discover are to engage students, teachers, and the general public in the excitement of ocean disco very through an interactive educational Web site. You can follow scientists on oceanographic research cruises by reading their daily cruise logs, viewing photos and video clips of the discoveries, and even e-mailing questions to the scientists and crew. WHOI has also included an "Educator's Companion" section with teaching strategies, activities, and assessments, making Dive and Discover an excellent resource for the classroom.

  7. Discovering Diabetes Complications: an Ontology Based Model.

    PubMed

    Daghistani, Tahani; Shammari, Riyad Al; Razzak, Muhammad Imran

    2015-12-01

    Diabetes is a serious disease that spread in the world dramatically. The diabetes patient has an average of risk to experience complications. Take advantage of recorded information to build ontology as information technology solution will help to predict patients who have average of risk level with certain complication. It is helpful to search and present patient's history regarding different risk factors. Discovering diabetes complications could be useful to prevent or delay the complications. We designed ontology based model, using adult diabetes patients' data, to discover the rules of diabetes with its complications in disease to disease relationship. Various rules between different risk factors of diabetes Patients and certain complications generated. Furthermore, new complications (diseases) might be discovered as new finding of this study, discovering diabetes complications could be useful to prevent or delay the complications. The system can identify the patients who are suffering from certain risk factors such as high body mass index (obesity) and starting controlling and maintaining plan.

  8. A rare type of Usher's syndrome.

    PubMed

    Antunica, Antonela Gverović; Kastelan, Snjezana; Bućan, Kajo; Ivanković, Mira; Radman, Maja; Karaman, Ksenija

    2013-12-01

    A case is presented of a very rare type of Usher's syndrome detected in a 30-year-old woman in her 28th week of pregnancy. She reported left eye visual impairment with a one-month history. She underwent standard ophthalmologic examination with additional procedures scheduled after childbirth, including fluorescein angiography, visual field (Goldman and Octopus) and electroretinography. Fundus examination revealed pallor of the optic disk, diffuse retinal blood vessel narrowing, no retinal pigmentation, left macular edema, vitreous liquefaction, and posterior vitreous detachment. Goldman perimetry showed narrowing of all isopters to 10 degrees, and Octopus perimetry showed peripheral decrease of retinal sensitivity. Electroretinography confirmed the diagnosis of retinitis pigmentosa sine pigmento. Upon collecting case history records, hearing disorders originating from childhood were discovered. To our knowledge, this type of retinitis in Usher's syndrome has been reported only once in the available literature.

  9. GiniClust: detecting rare cell types from single-cell gene expression data with Gini index.

    PubMed

    Jiang, Lan; Chen, Huidong; Pinello, Luca; Yuan, Guo-Cheng

    2016-07-01

    High-throughput single-cell technologies have great potential to discover new cell types; however, it remains challenging to detect rare cell types that are distinct from a large population. We present a novel computational method, called GiniClust, to overcome this challenge. Validation against a benchmark dataset indicates that GiniClust achieves high sensitivity and specificity. Application of GiniClust to public single-cell RNA-seq datasets uncovers previously unrecognized rare cell types, including Zscan4-expressing cells within mouse embryonic stem cells and hemoglobin-expressing cells in the mouse cortex and hippocampus. GiniClust also correctly detects a small number of normal cells that are mixed in a cancer cell population.

  10. Adrenal ganglioneuroma in a patient with polycystic ovarian disease (PCOD): a rare association.

    PubMed

    Kumar, Arvind; Singh, Vishwajeet; Sankhwar, Satyanarayan; Babu, Suresh

    2013-10-21

    Adrenal ganglioneuromas are rare, benign incidentalomas of a neural crest origin. A majority of these tumours are clinically silent and discovered on imaging for unrelated reasons. Polycystic ovarian disease (PCOD) is an endocrine disorder characterised by bilateral polycystic ovaries, anovulation leading to infertility, irregular menstrual cycles and features of androgen hormone excess. Herein we report a rare case of adrenal ganglioneuroma in a 14-year-old girl with PCOD. She was referred to us by the gynaecologist after incidental detection of adrenal mass on ultrasonography. Except for raised 24 h urinary metanephrines, rest of the hormones measured were in normal range. Transperitoneal adrenalectomy was performed and histopathology was suggestive of ganglioneuroma. Postoperative recovery was excellent and she is doing well. To our knowledge it is the first such type of case to be reported.

  11. A Systematic Mid-Infrared Survey of A Sample of Tidal Disruption Events Discovered by ZTF

    NASA Astrophysics Data System (ADS)

    Yan, Lin; Van, Sjoert; Kulkarni, Shri; Kasliwal, Mansi; Gezari, Suvi; Cenko, Brad; Blagorodnova, Nadia; Hung, Tiara

    2017-12-01

    Zwicky Transient Facility (ZTF) saw its first light (press release on Nov 14, 2017) and is currently in the commissioning phase. The science operation is scheduled to start on Feb 1, 2018. Based on the data from Palomar Transient Factory (PTF), ZTF is expected to discover 30 new tidal disruption events (TDE) in the centers of galaxies containing supermassive blackholes. TDEs are rare transient events, and have only been discovered in recent years by large area transient surveys. Observations of optically discovered TDEs appear to show common characteristics, including blackbody temperatures of a few 10,000K, derived bolometric peak luminosities of several 10^43 - 10^44 erg/s, and photospheric radius of 10^15 - 10^16 cm. These properties are in conflict with the classic TDE model predictions, which suggest an order of magnitude higher temperature and peak luminosity. One proposed explanation is the possible existence of a reprocessing gas layer which absorbs X-ray, UV/optical photons and produces a cooler spectral energy distribution (SED). So far, there are only two published mid-IR light curves of TDEs, each with two epochal data. To solve this mystery, we require higher cadence Spitzer observations of a sample of uniformly selected TDEs. Next year is the only opportunity to obtain the critical observations because Spitzer is expected to operate only to March 2019. We request 24.1 hours of Spitzer time to observe 7 ZTF TDEs. This will produce a unique legacy dataset for many future studies of physics of TDEs.

  12. DISCOVER-AQ Featured Articles

    Atmospheric Science Data Center

    2017-01-31

    ...     Not Your Average Video Traffic Report : Earth Matters Blogs  - DISCOVER-AQ planes have been flying over roadways, ... of air quality during “rush hour” and throughout the day. News Roundup: Arctic Ice, Spacesuit Satellites and More : Earth ...

  13. Lenomyrmex hoelldobleri: a new ant species discovered in the stomach of the dendrobatid poison frog, Oophaga sylvatica (Funkhouser)

    PubMed Central

    Rabeling, Christian; Sosa-Calvo, Jeffrey; O'Connell, Lauren A.; Coloma, Luis A.; Fernández, Fernando

    2016-01-01

    Abstract The ant genus Lenomyrmex was recently discovered and described from mid to high elevation rainforests in southern Central and northwestern South America. Lenomyrmex currently consists of six described species, which are only rarely collected. Here, we add a new species, Lenomyrmex hoelldobleri sp. n., which was discovered in a stomach content sample of the dendrobatid frog, Oophaga sylvatica, from northwestern Ecuador. Lenomyrmex hoelldobleri can be distinguished from other species in the genus by the presence of a well-developed petiolar node, whereas in all other species the node of the petiole is ill-defined. In addition to the shape of the petiolar node, Lenomyrmex hoelldobleri can be distinguished from the morphologically similar Lenomyrmex costatus by (i) the presence of the metanotal suture, (ii) the direction of the striae on dorsum of propodeum (concentrically transverse in Lenomyrmex hoelldobleri, longitudinal in Lenomyrmex costatus), (iii) the finely striate dorsum of postpetiole, (iv) its larger size, and (v) distinctly darker coloration. We also describe the gyne of Lenomyrmex foveolatus. This collection record from northwestern Ecuador extends the geographic distribution of Lenomyrmex foveolatus 400 km south from its previous record in Colombia. A revised taxonomic key to the workers and gynes of all described Lenomyrmex species is provided. We discuss the taxonomic relationship of Lenomyrmex hoelldobleri to other species in the genus and its biology based on the limited information that is currently available. Finally, we briefly discuss the feeding ecology of dendrobatid poison frogs in the context of providing a valuable source of rarely collected and cryptic new ant species. PMID:27853401

  14. Lenomyrmex hoelldobleri: a new ant species discovered in the stomach of the dendrobatid poison frog, Oophaga sylvatica (Funkhouser).

    PubMed

    Rabeling, Christian; Sosa-Calvo, Jeffrey; O'Connell, Lauren A; Coloma, Luis A; Fernández, Fernando

    2016-01-01

    The ant genus Lenomyrmex was recently discovered and described from mid to high elevation rainforests in southern Central and northwestern South America. Lenomyrmex currently consists of six described species, which are only rarely collected. Here, we add a new species, Lenomyrmex hoelldobleri sp. n. , which was discovered in a stomach content sample of the dendrobatid frog, Oophaga sylvatica , from northwestern Ecuador. Lenomyrmex hoelldobleri can be distinguished from other species in the genus by the presence of a well-developed petiolar node, whereas in all other species the node of the petiole is ill-defined. In addition to the shape of the petiolar node, Lenomyrmex hoelldobleri can be distinguished from the morphologically similar Lenomyrmex costatus by (i) the presence of the metanotal suture, (ii) the direction of the striae on dorsum of propodeum (concentrically transverse in Lenomyrmex hoelldobleri , longitudinal in Lenomyrmex costatus ), (iii) the finely striate dorsum of postpetiole, (iv) its larger size, and (v) distinctly darker coloration. We also describe the gyne of Lenomyrmex foveolatus . This collection record from northwestern Ecuador extends the geographic distribution of Lenomyrmex foveolatus 400 km south from its previous record in Colombia. A revised taxonomic key to the workers and gynes of all described Lenomyrmex species is provided. We discuss the taxonomic relationship of Lenomyrmex hoelldobleri to other species in the genus and its biology based on the limited information that is currently available. Finally, we briefly discuss the feeding ecology of dendrobatid poison frogs in the context of providing a valuable source of rarely collected and cryptic new ant species.

  15. Discovering Diabetes Complications: an Ontology Based Model

    PubMed Central

    Daghistani, Tahani; Shammari, Riyad Al; Razzak, Muhammad Imran

    2015-01-01

    Background: Diabetes is a serious disease that spread in the world dramatically. The diabetes patient has an average of risk to experience complications. Take advantage of recorded information to build ontology as information technology solution will help to predict patients who have average of risk level with certain complication. It is helpful to search and present patient’s history regarding different risk factors. Discovering diabetes complications could be useful to prevent or delay the complications. Method: We designed ontology based model, using adult diabetes patients’ data, to discover the rules of diabetes with its complications in disease to disease relationship. Result: Various rules between different risk factors of diabetes Patients and certain complications generated. Furthermore, new complications (diseases) might be discovered as new finding of this study, discovering diabetes complications could be useful to prevent or delay the complications. Conclusion: The system can identify the patients who are suffering from certain risk factors such as high body mass index (obesity) and starting controlling and maintaining plan. PMID:26862251

  16. [An ophthalmologic diagnostic error leading to a rare systemic diagnosis: Erdheim-Chester disease].

    PubMed

    Gilles, M; Alberti, N; Seguy, C; Leger, F; Frulio, N; Pechmeja, J; Longueville, E; Korobelnik, J-F

    2014-05-01

    Erdheim-Chester disease is a rare systemic disease. The diagnosis is difficult due to significant clinical and morphological polymorphism. Orbital involvement is rare, but constitutes a classic means of detection. We report the case of a 60-year-old man, who consulted for evaluation of bilateral retro-orbital tumors. These tumors had been discovered on head CT two years previously during work-up of proptosis. Two biopsies were performed. The first one revealed polymorphous inflammatory tissue. The second one revealed intense granulomatous reaction, rich in non-specific foamy histiocytes. Thoracic-abdominal-pelvic CT scan detected peri-aortic and retroperitoneal infiltration. The association of these signs pointed to a diagnosis of Erdheim-Chester disease, confirmed by the re-examination of the histological samples. Erdheim-Chester disease is a rare non-Langerhans histiocytosis with a specific tropism for perivascular and fatty connective tissue. The cause is not known. The diagnosis of this systemic disease is histological. In the case of bilateral intra-orbital tumors, the diagnosis of Erdheim-Chester disease must be considered. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Cor triatriatum dexter, atrial septal defects, and pulmonary stenosis-a rare association.

    PubMed

    Simsek, Ziya; Koza, Yavuzer; Tas, Hakan

    2014-04-01

    Cor triatriatum dexter (CTD) is an extremely rare congenital anomaly in which the right atrium is divided into 2 chambers by a membrane. The estimated incidence of cor triatriatum has been reported as 0.1% of congenital cardiac malformations. The septation of the right atrium in the setting of CTD is the result of failed resorption of the right valve of the sinus venosus. This results in anterolateral and posteromedial portions of the divided right atrium. CTD can be diagnosed at any age, especially if it is incidentally discovered. © 2014, Wiley Periodicals, Inc.

  18. DISCOVER AQ Research Plane Arrives

    NASA Image and Video Library

    2011-06-28

    James Crawford, principal investigator and scientist based at NASA’s Langley Research Center in Hampton, Va., talks about the DISCOVER-AQ project on board the P-3B NASA research aircraft at Baltimore/Washington International Thurgood Marshall Airport, Tuesday, June 28, 2011, in Baltimore, Md. The aircraft is part of a month-long field campaign designed to improve satellite measurements of air pollution. The name of the experiment -- Deriving Information on Surface conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER -- AQ) -- is a mouthful, but its purpose is simple. Come July, the aircraft will be flying spirals over six ground stations in Maryland. Photo Credit: (NASA/Paul E. Alers)

  19. Funding resources for rare disease research.

    PubMed

    Stehr, F; Forkel, M

    2013-11-01

    Research is an expensive venture requiring multiple sources of funding for small projects that test new theories, large projects to make major advancements, training the next generation of researchers and facilitating meetings to share findings and support collaboration. For rare conditions, such as Batten disease, research funds can be difficult to find. To see how investigators supported their work in the past, we did a key word search of the Acknowledgement Section of peer-reviewed literature published in Batten disease in the last 6.5 years. Interestingly, we discovered 193 separate funding sources. The authors hope that, by showing where funds are available, we will enable Batten disease researchers to continue their pursuits and expand their studies; moving key findings from discovery to application phases. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Whole-exome sequencing identifies common and rare variant metabolic QTLs in a Middle Eastern population.

    PubMed

    Yousri, Noha A; Fakhro, Khalid A; Robay, Amal; Rodriguez-Flores, Juan L; Mohney, Robert P; Zeriri, Hassina; Odeh, Tala; Kader, Sara Abdul; Aldous, Eman K; Thareja, Gaurav; Kumar, Manish; Al-Shakaki, Alya; Chidiac, Omar M; Mohamoud, Yasmin A; Mezey, Jason G; Malek, Joel A; Crystal, Ronald G; Suhre, Karsten

    2018-01-23

    Metabolomics-genome-wide association studies (mGWAS) have uncovered many metabolic quantitative trait loci (mQTLs) influencing human metabolic individuality, though predominantly in European cohorts. By combining whole-exome sequencing with a high-resolution metabolomics profiling for a highly consanguineous Middle Eastern population, we discover 21 common variant and 12 functional rare variant mQTLs, of which 45% are novel altogether. We fine-map 10 common variant mQTLs to new metabolite ratio associations, and 11 common variant mQTLs to putative protein-altering variants. This is the first work to report common and rare variant mQTLs linked to diseases and/or pharmacological targets in a consanguineous Arab cohort, with wide implications for precision medicine in the Middle East.

  1. Adrenal ganglioneuroma in a patient with polycystic ovarian disease (PCOD): a rare association

    PubMed Central

    Kumar, Arvind; Singh, Vishwajeet; Sankhwar, Satyanarayan; Babu, Suresh

    2013-01-01

    Adrenal ganglioneuromas are rare, benign incidentalomas of a neural crest origin. A majority of these tumours are clinically silent and discovered on imaging for unrelated reasons. Polycystic ovarian disease (PCOD) is an endocrine disorder characterised by bilateral polycystic ovaries, anovulation leading to infertility, irregular menstrual cycles and features of androgen hormone excess. Herein we report a rare case of adrenal ganglioneuroma in a 14-year-old girl with PCOD. She was referred to us by the gynaecologist after incidental detection of adrenal mass on ultrasonography. Except for raised 24 h urinary metanephrines, rest of the hormones measured were in normal range. Transperitoneal adrenalectomy was performed and histopathology was suggestive of ganglioneuroma. Postoperative recovery was excellent and she is doing well. To our knowledge it is the first such type of case to be reported. PMID:24145507

  2. 'Rare biosphere' bacteria as key phenanthrene degraders in coastal seawaters.

    PubMed

    Sauret, Caroline; Séverin, Tatiana; Vétion, Gilles; Guigue, Catherine; Goutx, Madeleine; Pujo-Pay, Mireille; Conan, Pascal; Fagervold, Sonja K; Ghiglione, Jean-François

    2014-11-01

    By coupling DNA-SIP and pyrosequencing approaches, we identified Cycloclasticus sp. as a keystone degrader of polycyclic aromatic hydrocarbons (PAH) despite being a member of the 'rare biosphere' in NW Mediterranean seawaters. We discovered novel PAH-degrading bacteria (Oceanibaculum sp., Sneathiella sp.) and we identified other groups already known to possess this function (Alteromonas sp., Paracoccus sp.). Together with Cycloclasticus sp., these groups contributed to potential in situ phenanthrene degradation at a rate >0.5 mg l(-1) day(-1), sufficient to account for a considerable part of PAH degradation. Further, we characterized the PAH-tolerant bacterial communities, which were much more diverse in the polluted site by comparison to unpolluted marine references. PAH-tolerant bacteria were also members of the rare biosphere, such as Glaciecola sp. Collectively, these data show the complex interactions between PAH-degraders and PAH-tolerant bacteria and provide new insights for the understanding of the functional ecology of marine bacteria in polluted waters. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. A Rare Clinical Presentation of Darier's Disease

    PubMed Central

    Ferizi, Mybera; Begolli-Gerqari, Antigona; Luzar, Bostjan; Kurshumliu, Fisnik; Ferizi, Mergita

    2013-01-01

    Darier's disease, also known as keratosis follicularis or dyskeratosis follicularis, is a rare disorder of keratinization. It is an autosomal dominant genodermatosis with high penetrance and variable expressivity. Its manifestation appears as hyperkeratotic papules, primarily affecting seborrheic areas on the head, neck, and thorax and less frequently on the oral mucosa. When oral manifestations are present, the palatal and alveolar mucosae are primarily affected. They are usually asymptomatic and are discovered in routine dental examination. Histologically, the lesions are presented as suprabasal clefts in the epithelium with acantholytic and dyskeratotic cells represented by “corps ronds and grains”. This paper reports a case of a 53-year-old woman that was admitted to our clinic with more than 10-year history of keratotic papules, presented on the hands and feet, nose, ears, genitalia, and whitish lesions on palatal mucosae. PMID:23573430

  4. Introduction to Deep Sequencing and Its Application to Drug Addiction Research with a Focus on Rare Variants

    PubMed Central

    Wang, Shaolin; Yang, Zhongli; Ma, Jennie Z.; Payne, Thomas J.; Li, Ming D

    2013-01-01

    Through linkage analysis, candidate gene approach, and genome-wide association studies (GWAS), many genetic susceptibility factors for substance dependence have been discovered, such as the alcohol dehydrogenase gene (ALDH2) for alcohol dependence (AD) and nicotinic acetylcholine receptor (nAChR) subunit variants on chromosomes 8 and 15 for nicotine dependence (ND). However, these confirmed genetic factors contribute only a small portion of the heritability responsible for each addiction. Among many potential factors, rare variants in those identified and unidentified susceptibility genes are supposed to contribute greatly to the missing heritability. Several studies focusing on rare variants have been conducted by taking advantage of next-generation sequencing technologies, which revealed that some rare variants of nAChR subunits are associated with ND in both genetic and functional studies. However, these studies investigated variants for only a small number of genes and need to be expanded to broad regions/genes in a larger population. This review presents an update on recently developed methods for rare-variant identification and association analysis and on studies focused on rare-variant discovery and function related to addictions. PMID:23990377

  5. Helping Your Children Discover.

    ERIC Educational Resources Information Center

    Schroepfer, Dorothy; Yeaton, Charles

    Children discover many things about themselves, about the world around them, and about words and language, before they go to school. This booklet was prepared to guide parents in helping their children make such discoveries in preparation for the demands of learning in school. Activities are suggested for developing children's self-confidence,…

  6. Drosophila Models of Parkinson's Disease: Discovering Relevant Pathways and Novel Therapeutic Strategies

    PubMed Central

    Muñoz-Soriano, Verónica; Paricio, Nuria

    2011-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder and is mainly characterized by the selective and progressive loss of dopaminergic neurons, accompanied by locomotor defects. Although most PD cases are sporadic, several genes are associated with rare familial forms of the disease. Analyses of their function have provided important insights into the disease process, demonstrating that three types of cellular defects are mainly involved in the formation and/or progression of PD: abnormal protein aggregation, oxidative damage, and mitochondrial dysfunction. These studies have been mainly performed in PD models created in mice, fruit flies, and worms. Among them, Drosophila has emerged as a very valuable model organism in the study of either toxin-induced or genetically linked PD. Indeed, many of the existing fly PD models exhibit key features of the disease and have been instrumental to discover pathways relevant for PD pathogenesis, which could facilitate the development of therapeutic strategies. PMID:21512585

  7. Discovering interesting molecular substructures for molecular classification.

    PubMed

    Lam, Winnie W M; Chan, Keith C C

    2010-06-01

    Given a set of molecular structure data preclassified into a number of classes, the molecular classification problem is concerned with the discovering of interesting structural patterns in the data so that "unseen" molecules not originally in the dataset can be accurately classified. To tackle the problem, interesting molecular substructures have to be discovered and this is done typically by first representing molecular structures in molecular graphs, and then, using graph-mining algorithms to discover frequently occurring subgraphs in them. These subgraphs are then used to characterize different classes for molecular classification. While such an approach can be very effective, it should be noted that a substructure that occurs frequently in one class may also does occur in another. The discovering of frequent subgraphs for molecular classification may, therefore, not always be the most effective. In this paper, we propose a novel technique called mining interesting substructures in molecular data for classification (MISMOC) that can discover interesting frequent subgraphs not just for the characterization of a molecular class but also for the distinguishing of it from the others. Using a test statistic, MISMOC screens each frequent subgraph to determine if they are interesting. For those that are interesting, their degrees of interestingness are determined using an information-theoretic measure. When classifying an unseen molecule, its structure is then matched against the interesting subgraphs in each class and a total interestingness measure for the unseen molecule to be classified into a particular class is determined, which is based on the interestingness of each matched subgraphs. The performance of MISMOC is evaluated using both artificial and real datasets, and the results show that it can be an effective approach for molecular classification.

  8. DISCOVER in Middle School: Identifying Gifted Minority Students

    ERIC Educational Resources Information Center

    Sarouphim, Ketty M.

    2004-01-01

    The purpose of this study was to examine the validity of the grades 6-8 version of DISCOVER, a performance-based assessment, and investigate its effectiveness in identifying gifted minority students. Questions examined the alignment between DISCOVER and Gardner's (1983) theory of multiple intelligences (MI) and assessed gender and ethnic…

  9. Discover: What Is Public Health?

    MedlinePlus

    ... Resources Contact About Membership Contact Discover What is Public Health? Public health protects and improves the health of individuals, families, communities, and populations, locally and globally. Public health is personal. Public health professionals focus on preventing ...

  10. NGS Technologies as a Turning Point in Rare Disease Research, Diagnosis and Treatment

    PubMed Central

    Fernández-Marmiesse, Ana; Gouveia, Sofía; Couce, María L.

    2018-01-01

    Approximately 25-50 million Americans, 30 million Europeans, and 8% of the Aus-tralian population have a rare disease. Rare diseases are thus a common problem for clini-cians and account for enormous healthcare costs worldwide due to the difficulty of establish-ing a specific diagnosis. In this article, we review the milestones achieved in our understanding of rare diseases since the emergence of next-generation sequencing (NGS) technologies and analyze how these advances have influenced research and diagnosis. The first half of this review describes how NGS has changed diagnostic workflows and provided an unprecedent-ed, simple way of discovering novel disease-associated genes. We focus particularly on meta-bolic and neurodevelopmental disorders. NGS has enabled cheap and rapid genetic diagnosis, highlighted the relevance of mosaic and de novo mutations, brought to light the wide pheno-typic spectrum of most genes, detected digenic inheritance or the presence of more than one rare disease in the same patient, and paved the way for promising new therapies. In the sec-ond part of the review, we look at the limitations and challenges of NGS, including determina-tion of variant causality, the loss of variants in coding and non-coding regions, and the detec-tion of somatic mosaicism variants and epigenetic mutations, and discuss how these can be overcome in the near future. PMID:28721829

  11. NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment.

    PubMed

    Fernandez-Marmiesse, Ana; Gouveia, Sofia; Couce, Maria L

    2018-01-30

    Approximately 25-50 million Americans, 30 million Europeans, and 8% of the Australian population have a rare disease. Rare diseases are thus a common problem for clinicians and account for enormous healthcare costs worldwide due to the difficulty of establishing a specific diagnosis. In this article, we review the milestones achieved in our understanding of rare diseases since the emergence of next-generation sequencing (NGS) technologies and analyze how these advances have influenced research and diagnosis. The first half of this review describes how NGS has changed diagnostic workflows and provided an unprecedented, simple way of discovering novel disease-associated genes. We focus particularly on metabolic and neurodevelopmental disorders. NGS has enabled cheap and rapid genetic diagnosis, highlighted the relevance of mosaic and de novo mutations, brought to light the wide phenotypic spectrum of most genes, detected digenic inheritance or the presence of more than one rare disease in the same patient, and paved the way for promising new therapies. In the second part of the review, we look at the limitations and challenges of NGS, including determination of variant causality, the loss of variants in coding and non-coding regions, and the detection of somatic mosaicism variants and epigenetic mutations, and discuss how these can be overcome in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Discover: An Educational Opportunity for Women in Transition.

    ERIC Educational Resources Information Center

    Willson, Linda M.; And Others

    The Discover program is a program for women who want to become self-sufficient and self-supporting. Clients of the program may be separated or divorced, single mothers, or married to an underemployed spouse. The Discover program involves career exploration in the hope that its graduates will enter an occupational training program. The goals of the…

  13. Discover Supercomputer 5

    NASA Image and Video Library

    2017-12-08

    Two rows of the “Discover” supercomputer at the NASA Center for Climate Simulation (NCCS) contain more than 4,000 computer processors. Discover has a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

  14. Discover Supercomputer 3

    NASA Image and Video Library

    2017-12-08

    The heart of the NASA Center for Climate Simulation (NCCS) is the “Discover” supercomputer. In 2009, NCCS added more than 8,000 computer processors to Discover, for a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

  15. Discover Supercomputer 2

    NASA Image and Video Library

    2017-12-08

    The heart of the NASA Center for Climate Simulation (NCCS) is the “Discover” supercomputer. In 2009, NCCS added more than 8,000 computer processors to Discover, for a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

  16. Discover Supercomputer 4

    NASA Image and Video Library

    2017-12-08

    This close-up view highlights one row—approximately 2,000 computer processors—of the “Discover” supercomputer at the NASA Center for Climate Simulation (NCCS). Discover has a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

  17. Discover Supercomputer 1

    NASA Image and Video Library

    2017-12-08

    The heart of the NASA Center for Climate Simulation (NCCS) is the “Discover” supercomputer. In 2009, NCCS added more than 8,000 computer processors to Discover, for a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

  18. Discovering system requirements

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

    Bahill, A.T.; Bentz, B.; Dean, F.F.

    1996-07-01

    Cost and schedule overruns are often caused by poor requirements that are produced by people who do not understand the requirements process. This report provides a high-level overview of the system requirements process, explaining types, sources, and characteristics of good requirements. System requirements, however, are seldom stated by the customer. Therefore, this report shows ways to help you work with your customer to discover the system requirements. It also explains terminology commonly used in the requirements development field, such as verification, validation, technical performance measures, and the various design reviews.

  19. Merkel Cell Polyomavirus: A Newly Discovered Human Virus with Oncogenic Potential

    PubMed Central

    Spurgeon, Megan E.; Lambert, Paul F.

    2012-01-01

    A marked escalation in the rate of discovery of new types of human polyomavirus has occurred over the last five years largely owing to recent technological advances in their detection. Among the newly discovered viruses, Merkel Cell Polyomavirus (MCPyV or MCV) has gained the most attention due to its link with a rare human cancer. Infection with MCPyV is common in the human population, and the virus is detected in several anatomical locations, but most frequently in skin. Study of MCPyV molecular virology has been complicated by the lack of straightforward cell culture models, but recent in vitro studies are making strides towards understanding the virus life cycle, its cellular tropism, and mode of transmission. While MCPyV shares several traditional traits with other human polyomaviruses, the burst of research since its discovery reveals insight into a virus with many unique genetic and mechanistic features. The evidence for a causal link between MCPyV and the rare neuroendocrine cancer, Merkel Cell Carcinoma (MCC), is compelling. A majority of MCCs contain clonally integrated viral DNA, express viral T antigen transcripts and protein, and exhibit an addiction to the viral large T and small t antigen oncoproteins. The MCPyV large T antigen contains MCC tumor-specific mutations that ablate its replication capacity but preserve its oncogenic functions, and the small t antigen promotes an environment favorable for cap-dependent translation. The mechanisms of MCPyV-induced transformation have not been fully elucidated, but the likely etiological role of this new polyomavirus in human cancer provides a strong opportunity to expand knowledge of virus-host interactions and viral oncology. PMID:23217622

  20. Biological Activity of Recently Discovered Halogenated Marine Natural Products

    PubMed Central

    Gribble, Gordon W.

    2015-01-01

    This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included. PMID:26133553

  1. Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

    PubMed Central

    Stakaitytė, Gabrielė; Wood, Jennifer J.; Knight, Laura M.; Abdul-Sada, Hussein; Adzahar, Noor Suhana; Nwogu, Nnenna; Macdonald, Andrew; Whitehouse, Adrian

    2014-01-01

    A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC. PMID:24978434

  2. Aberrant systemic arterial supply to normal lung arising from the proper hepatic artery discovered during transarterial chemoembolization.

    PubMed

    Walsworth, Matthew K; Yap, Felix Y; McWilliams, Justin P

    2015-11-01

    We report a rare case of dual arterial supply to an otherwise normal lung discovered incidentally during initial angiography performed with the intent of chemoembolization of hepatocellular carcinoma. In addition to normal hepatic arterial supply, the proper hepatic artery provided systemic arterial supply to the lower lobe of the left lung. Subsequent chest computed tomography angiography demonstrated a normal tracheobronchial tree and normal pulmonary arterial supply to the lung. Although other anatomic variants have been reported, there are no other reported cases of systemic arterial supply from the proper hepatic artery to the lung. Identifying systemic arterial supply to the lung during angiography is important while performing transcatheter chemoembolization or radioembolization in the liver in order to minimize non-target embolization of the lung.

  3. Discover Assessment and Restoration Data | NOAA Gulf Spill Restoration

    Science.gov Websites

    Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story Archive Home Discover Assessment and Restoration Data Discover Assessment and Restoration Data During the course of the damage assessment, we collected a large amount of data to document the location and extent

  4. Internal Carotid Artery Agenesis with an Intercavernous Anastomosis: A Rare Case.

    PubMed

    Erdogan, Mucahid; Senadim, Songul; Ince Yasinoglu, K Nur; Selcuk, H Hakan; Atakli, H Dilek

    2017-10-01

    Agenesis of the internal carotid artery (ICA) is a rare vascular anomaly that was first observed postmortem. Various anastomoses supply the distal vessels at the site of agenesis. Of these anastomoses, an intercavernous anastomosis is very rare. This paper presents a patient with ischemic stroke in whom we discovered left ICA agenesis and an ipsilateral intercavernous anastomosis. A 58-year-old man with a history of myocardial infarction and diabetes mellitus presented with sudden-onset difficulty in speaking, numbness on the left side of the face, and weakness of the left arm and leg. Neurological examination revealed dysarthria, left facial paralysis, left hemiparesis, and bilateral absence of the plantar reflexes. Diffusion-weighted magnetic resonance imaging showed a right middle cerebral artery (MCA) infarction. On cranial and cervical magnetic resonance angiography, the left ICA could not be seen distal to the bifurcation; the left MCA was supplied through an intercavernous anastomosis between the right ICA and the left ICA. Cranial computed tomography (CT) revealed the absence of the left carotid canal. Digital subtraction angiography led to a diagnosis of left ICA agenesis with an intercavernous anastomosis. The patient was discharged on acetylsalicylic acid and warfarin. ICA agenesis with an intercavernous anastomosis is a rare vascular anomaly that should be differentiated from secondary causes of ICA stenosis and occlusions by showing agenesis of the carotid canal on cranial CT. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. A Rare Vehicle-Assisted Ligature Hanging: Suicide at the Wheel.

    PubMed

    Barranco, Rosario; Caputo, Fiorella; Bonsignore, Alessandro; Fraternali Orcioni, Giulio; Ventura, Francesco

    2018-03-01

    Suicide by hanging inside a motor vehicle is a rare occurrence. A 48-year-old woman suffering from major depression was found having agonal breathing inside her automobile. A 20-mm diameter blue nylon rope was wrapped tightly around her neck, with its other end tied to a nearby wooden fence post. Despite resuscitation attempts, she was declared deceased after several minutes. The vehicle was located in an area with a slight downward slope. The motor was off. It was in neutral gear, with the parking brake disengaged. Consequently, the gravitational forces, attributable to the mass of the vehicle and the declivity of the terrain, caused the rope to tighten.The dynamics fulfill the criteria for a partial hanging, given the difference in height between the point at which the rope was secured to the post and woman's neck, which in turn presented the typical oblique upward groove.This case, thus, represents a unique mode of partial hanging inside a passenger vehicle, rarely reported in the literature. The relative lack of internal injury is also noteworthy, along with the fact that the victim was discovered while still alive. The latter feature can be explained by the absence of the sudden or violent acceleration forces that can be generated with the engine on.

  6. Discovering body site and severity modifiers in clinical texts.

    PubMed

    Dligach, Dmitriy; Bethard, Steven; Becker, Lee; Miller, Timothy; Savova, Guergana K

    2014-01-01

    To research computational methods for discovering body site and severity modifiers in clinical texts. We cast the task of discovering body site and severity modifiers as a relation extraction problem in the context of a supervised machine learning framework. We utilize rich linguistic features to represent the pairs of relation arguments and delegate the decision about the nature of the relationship between them to a support vector machine model. We evaluate our models using two corpora that annotate body site and severity modifiers. We also compare the model performance to a number of rule-based baselines. We conduct cross-domain portability experiments. In addition, we carry out feature ablation experiments to determine the contribution of various feature groups. Finally, we perform error analysis and report the sources of errors. The performance of our method for discovering body site modifiers achieves F1 of 0.740-0.908 and our method for discovering severity modifiers achieves F1 of 0.905-0.929. Results indicate that both methods perform well on both in-domain and out-domain data, approaching the performance of human annotators. The most salient features are token and named entity features, although syntactic dependency features also contribute to the overall performance. The dominant sources of errors are infrequent patterns in the data and inability of the system to discern deeper semantic structures. We investigated computational methods for discovering body site and severity modifiers in clinical texts. Our best system is released open source as part of the clinical Text Analysis and Knowledge Extraction System (cTAKES).

  7. Galaxy evolution. Quasar quartet embedded in giant nebula reveals rare massive structure in distant universe.

    PubMed

    Hennawi, Joseph F; Prochaska, J Xavier; Cantalupo, Sebastiano; Arrigoni-Battaia, Fabrizio

    2015-05-15

    All galaxies once passed through a hyperluminous quasar phase powered by accretion onto a supermassive black hole. But because these episodes are brief, quasars are rare objects typically separated by cosmological distances. In a survey for Lyman-α emission at redshift z ≈ 2, we discovered a physical association of four quasars embedded in a giant nebula. Located within a substantial overdensity of galaxies, this system is probably the progenitor of a massive galaxy cluster. The chance probability of finding a quadruple quasar is estimated to be ∼10(-7), implying a physical connection between Lyman-α nebulae and the locations of rare protoclusters. Our findings imply that the most massive structures in the distant universe have a tremendous supply (≃10(11) solar masses) of cool dense (volume density ≃ 1 cm(-3)) gas, which is in conflict with current cosmological simulations. Copyright © 2015, American Association for the Advancement of Science.

  8. Identification of a rare coding variant in TREM2 in a Chinese individual with Alzheimer's disease.

    PubMed

    Bonham, Luke W; Sirkis, Daniel W; Fan, Jia; Aparicio, Renan E; Tse, Marian; Ramos, Eliana Marisa; Wang, Qing; Coppola, Giovanni; Rosen, Howard J; Miller, Bruce L; Yokoyama, Jennifer S

    2017-02-01

    Rare variation in the TREM2 gene is associated with a broad spectrum of neurodegenerative disorders including Alzheimer's disease (AD). TREM2 encodes a receptor expressed in microglia which is thought to influence neurodegeneration by sensing damage signals and regulating neuroinflammation. Many of the variants reported to be associated with AD, including the rare R47H variant, were discovered in populations of European ancestry and have not replicated in diverse populations from other genetic backgrounds. We utilized a cohort of elderly Chinese individuals diagnosed as cognitively normal, or with mild cognitive impairment or AD to identify a rare variant, A192T, present in a single patient diagnosed with AD. We characterized this variant using biochemical cell surface expression assays and found that it significantly altered cell surface expression of the TREM2 protein. Together these data provide evidence that the A192T variant in TREM2 could contribute risk for AD. This study underscores the increasingly recognized role of immune-related processes in AD and highlights the importance of including diverse populations in research to identify genetic variation that contributes risk for AD and other neurodegenerative disorders.

  9. Discovering Technicolor

    NASA Astrophysics Data System (ADS)

    Andersen, J. R.; Antipin, O.; Azuelos, G.; Del Debbio, L.; Del Nobile, E.; Di Chiara, S.; Hapola, T.; Järvinen, M.; Lowdon, P. J.; Maravin, Y.; Masina, I.; Nardecchia, M.; Pica, C.; Sannino, F.

    2011-09-01

    We provide a pedagogical introduction to extensions of the Standard Model in which the Higgs is composite. These extensions are known as models of dynamical electroweak symmetry breaking or, in brief, Technicolor. Material covered includes: motivations for Technicolor, the construction of underlying gauge theories leading to minimal models of Technicolor, the comparison with electroweak precision data, the low-energy effective theory, the spectrum of the states common to most of the Technicolor models, the decays of the composite particles and the experimental signals at the Large Hadron Collider. The level of the presentation is aimed at readers familiar with the Standard Model but who have little or no prior exposure to Technicolor. Several extensions of the Standard Model featuring a composite Higgs can be reduced to the effective Lagrangian introduced in the text. We establish the relevant experimental benchmarks for Vanilla, Running, Walking, and Custodial Technicolor, and a natural fourth family of leptons, by laying out the framework to discover these models at the Large Hadron Collider.

  10. Discovering body site and severity modifiers in clinical texts

    PubMed Central

    Dligach, Dmitriy; Bethard, Steven; Becker, Lee; Miller, Timothy; Savova, Guergana K

    2014-01-01

    Objective To research computational methods for discovering body site and severity modifiers in clinical texts. Methods We cast the task of discovering body site and severity modifiers as a relation extraction problem in the context of a supervised machine learning framework. We utilize rich linguistic features to represent the pairs of relation arguments and delegate the decision about the nature of the relationship between them to a support vector machine model. We evaluate our models using two corpora that annotate body site and severity modifiers. We also compare the model performance to a number of rule-based baselines. We conduct cross-domain portability experiments. In addition, we carry out feature ablation experiments to determine the contribution of various feature groups. Finally, we perform error analysis and report the sources of errors. Results The performance of our method for discovering body site modifiers achieves F1 of 0.740–0.908 and our method for discovering severity modifiers achieves F1 of 0.905–0.929. Discussion Results indicate that both methods perform well on both in-domain and out-domain data, approaching the performance of human annotators. The most salient features are token and named entity features, although syntactic dependency features also contribute to the overall performance. The dominant sources of errors are infrequent patterns in the data and inability of the system to discern deeper semantic structures. Conclusions We investigated computational methods for discovering body site and severity modifiers in clinical texts. Our best system is released open source as part of the clinical Text Analysis and Knowledge Extraction System (cTAKES). PMID:24091648

  11. [Healthcare services for people in Lower Saxony (Germany) suffering from a rare disease: Findings from a survey among medical professionals].

    PubMed

    Pauer, Frédéric; Pflaum, Uljana; Lührs, Verena; Frank, Martin; Graf von der Schulenburg, J-Matthias

    2016-01-01

    In the European Union, about 30 million people are affected by one of the 7,000 to 8,000 diseases being defined as rare. In Germany alone, an estimated 4 million people suffer from a rare disease. In many cases, therapeutic options and knowledge of specific rare diseases are strongly limited. The aim of this study was to identify the deficits and challenges confronting healthcare services for people suffering from a rare disease from the medical professional's perspective. As many as 530 medical professionals were invited to complete an online questionnaire, which was also available on the website of the General Medical Council of Lower Saxony. The questionnaire focused on questions in the following fields: structure of the medical care system; diagnosis and therapy; information sources and information exchange; and improvement of healthcare situation. Data were analyzed using IBM SPSS 22. We received 65 completed questionnaires. The evaluation indicates deficits in the medical services provided for people with a rare disease and shortcomings in the communication between clinical disciplines. In addition, diagnostic and therapeutic options are limited, and quality-tested information is rare. Many of the identified deficits have already been addressed in the German national plan of action for people affected by rare diseases. Furthermore, newly discovered deficits have been evaluated. The German government implemented healthcare structures to improve healthcare services for people with rare diseases. However, budget deficits for specialized structures have occurred inhibiting the expansion of healthcare services. Moreover, many patients need systemic treatment requiring the further development of interdisciplinary care. Copyright © 2016. Published by Elsevier GmbH.

  12. Did Viking discover life on Mars?

    NASA Technical Reports Server (NTRS)

    Klein, H. P.

    1999-01-01

    A major argument in the claim that life had been discovered during the Viking mission to Mars is that the results obtained in the Labeled Release (LR) experiment are analogous to those observed with terrestrial microorganisms. This assertion is critically examined and found to be implausible.

  13. Did Viking discover life on Mars?

    PubMed

    Klein, H P

    1999-12-01

    A major argument in the claim that life had been discovered during the Viking mission to Mars is that the results obtained in the Labeled Release (LR) experiment are analogous to those observed with terrestrial microorganisms. This assertion is critically examined and found to be implausible.

  14. A 15.7-Minute AM CVn Binary Discovered in K2

    NASA Astrophysics Data System (ADS)

    Green, M. J.; Hermes, J. J.; Marsh, T. R.; Steeghs, D. T. H.; Bell, Keaton J.; Littlefair, S. P.; Parsons, S. G.; Dennihy, E.; Fuchs, J. T.; Reding, J. S.; Kaiser, B. C.; Ashley, R. P.; Breedt, E.; Dhillon, V. S.; Gentile Fusillo, N. P.; Kerry, P.; Sahman, D. I.

    2018-04-01

    We present the discovery of SDSS J135154.46-064309.0, a short-period variable observed using 30-minute cadence photometry in K2 Campaign 6. Follow-up spectroscopy and high-speed photometry support a classification as a new member of the rare class of ultracompact accreting binaries known as AM CVn stars. The spectroscopic orbital period of 15.65 ± 0.12 minutes makes this system the fourth-shortest period AM CVn known, and the second system of this type to be discovered by the Kepler spacecraft. The K2 data show photometric periods at 15.7306 ± 0.0003 minutes, 16.1121 ± 0.0004 minutes and 664.82 ± 0.06 minutes, which we identify as the orbital period, superhump period, and disc precession period, respectively. From the superhump and orbital periods we estimate the binary mass ratio q = M2/M1 = 0.111 ± 0.005, though this method of mass ratio determination may not be well calibrated for helium-dominated binaries. This system is likely to be a bright foreground source of gravitational waves in the frequency range detectable by LISA, and may be of use as a calibration source if future studies are able to constrain the masses of its stellar components.

  15. A 15.7-minAM CVn binary discovered in K2

    NASA Astrophysics Data System (ADS)

    Green, M. J.; Hermes, J. J.; Marsh, T. R.; Steeghs, D. T. H.; Bell, Keaton J.; Littlefair, S. P.; Parsons, S. G.; Dennihy, E.; Fuchs, J. T.; Reding, J. S.; Kaiser, B. C.; Ashley, R. P.; Breedt, E.; Dhillon, V. S.; Gentile Fusillo, N. P.; Kerry, P.; Sahman, D. I.

    2018-07-01

    We present the discovery of SDSS J135154.46-064309.0, a short-period variable observed using 30-mincadence photometry in K2 Campaign 6. Follow-up spectroscopy and high-speed photometry support a classification as a new member of the rare class of ultracompact accreting binaries known as AM CVn stars. The spectroscopic orbital period of 15.65 ± 0.12 min makes this system the fourth-shortest-period AM CVn known, and the second system of this type to be discovered by the Kepler spacecraft. The K2 data show photometric periods at 15.7306 ± 0.0003 min, 16.1121 ± 0.0004 min, and 664.82 ± 0.06 min, which we identify as the orbital period, superhump period, and disc precession period, respectively. From the superhump and orbital periods we estimate the binary mass ratio q = M2/M1= 0.111 ± 0.005, though this method of mass ratio determination may not be well calibrated for helium-dominated binaries. This system is likely to be a bright foreground source of gravitational waves in the frequency range detectable by Laser Interferometer Space Antenna, and may be of use as a calibration source if future studies are able to constrain the masses of its stellar components.

  16. Discover the Cosmos - Bringing Cutting Edge Science to Schools across Europe

    NASA Astrophysics Data System (ADS)

    Doran, Rosa

    2015-03-01

    The fast growing number of science data repositories is opening enormous possibilities to scientists all over the world. The emergence of citizen science projects is engaging in science discovery a large number of citizens globally. Astronomical research is now a possibility to anyone having a computer and some form of data access. This opens a very interesting and strategic possibility to engage large audiences in the making and understanding of science. On another perspective it would be only natural to imagine that soon enough data mining will be an active part of the academic path of university or even secondary schools students. The possibility is very exciting but the road not very promising. Even in the most developed nations, where all schools are equipped with modern ICT facilities the use of such possibilities is still a very rare episode. The Galileo Teacher Training Program GTTP, a legacy of IYA2009, is participating in some of the most emblematic projects funded by the European Commission and targeting modern tools, resources and methodologies for science teaching. One of this projects is Discover the Cosmos which is aiming to target this issue by empowering educators with the necessary skills to embark on this innovative path: teaching science while doing science.

  17. Discovering novel subsystems using comparative genomics

    PubMed Central

    Ferrer, Luciana; Shearer, Alexander G.; Karp, Peter D.

    2011-01-01

    Motivation: Key problems for computational genomics include discovering novel pathways in genome data, and discovering functional interaction partners for genes to define new members of partially elucidated pathways. Results: We propose a novel method for the discovery of subsystems from annotated genomes. For each gene pair, a score measuring the likelihood that the two genes belong to a same subsystem is computed using genome context methods. Genes are then grouped based on these scores, and the resulting groups are filtered to keep only high-confidence groups. Since the method is based on genome context analysis, it relies solely on structural annotation of the genomes. The method can be used to discover new pathways, find missing genes from a known pathway, find new protein complexes or other kinds of functional groups and assign function to genes. We tested the accuracy of our method in Escherichia coli K-12. In one configuration of the system, we find that 31.6% of the candidate groups generated by our method match a known pathway or protein complex closely, and that we rediscover 31.2% of all known pathways and protein complexes of at least 4 genes. We believe that a significant proportion of the candidates that do not match any known group in E.coli K-12 corresponds to novel subsystems that may represent promising leads for future laboratory research. We discuss in-depth examples of these findings. Availability: Predicted subsystems are available at http://brg.ai.sri.com/pwy-discovery/journal.html. Contact: lferrer@ai.sri.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21775308

  18. iPTF17cw: An Engine-driven Supernova Candidate Discovered Independent of a Gamma-Ray Trigger

    NASA Astrophysics Data System (ADS)

    Corsi, A.; Cenko, S. B.; Kasliwal, M. M.; Quimby, R.; Kulkarni, S. R.; Frail, D. A.; Goldstein, A. M.; Blagorodnova, N.; Connaughton, V.; Perley, D. A.; Singer, L. P.; Copperwheat, C. M.; Fremling, C.; Kupfer, T.; Piascik, A. S.; Steele, I. A.; Taddia, F.; Vedantham, H.; Kutyrev, A.; Palliyaguru, N. T.; Roberts, O.; Sollerman, J.; Troja, E.; Veilleux, S.

    2017-09-01

    We present the discovery, classification, and radio-to-X-ray follow-up observations of iPTF17cw, a broad-lined (BL) type Ic supernova (SN) discovered by the intermediate Palomar Transient Factory (iPTF). Although it is unrelated to the gravitational wave trigger, this SN was discovered as a happy by-product of the extensive observational campaign dedicated to the follow-up of Advanced LIGO event GW 170104. The spectroscopic properties and inferred peak bolometric luminosity of iPTF17cw are most similar to the gamma-ray-burst (GRB)-associated SN, SN 1998bw, while the shape of the r-band light curve is most similar to that of the relativistic SN, SN 2009bb. Karl G. Jansky Very Large Array (VLA) observations of the iPTF17cw field reveal a radio counterpart ≈10 times less luminous than SN 1998bw, and with a peak radio luminosity comparable to that of SN 2006aj/GRB 060218 and SN 2010bh/GRB 100316D. Our radio observations of iPTF17cw imply a relativistically expanding outflow. However, further late-time observations with the VLA in its most extended configuration are needed to confirm fading of the iPTF17cw radio counterpart at all frequencies. X-ray observations carried out with Chandra reveal the presence of an X-ray counterpart with a luminosity similar to that of SN 2010bh/GRB 100316D. Searching the Fermi catalog for possible γ-rays reveals that GRB 161228B is spatially and temporally compatible with iPTF17cw. The similarity to SN 1998bw and SN 2009bb, the radio and X-ray detections, and the potential association with GRB 161228B all point to iPTF17cw being a new candidate member of the rare sample of optically discovered engine-driven BL-Ic SNe associated with relativistic ejecta.

  19. iPTF17cw: An Engine-driven Supernova Candidate Discovered Independent of a Gamma-Ray Trigger

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

    Corsi, A.; Palliyaguru, N. T.; Cenko, S. B.

    We present the discovery, classification, and radio-to-X-ray follow-up observations of iPTF17cw, a broad-lined (BL) type Ic supernova (SN) discovered by the intermediate Palomar Transient Factory (iPTF). Although it is unrelated to the gravitational wave trigger, this SN was discovered as a happy by-product of the extensive observational campaign dedicated to the follow-up of Advanced LIGO event GW 170104. The spectroscopic properties and inferred peak bolometric luminosity of iPTF17cw are most similar to the gamma-ray-burst (GRB)-associated SN, SN 1998bw, while the shape of the r -band light curve is most similar to that of the relativistic SN, SN 2009bb. Karl G.more » Jansky Very Large Array (VLA) observations of the iPTF17cw field reveal a radio counterpart ≈10 times less luminous than SN 1998bw, and with a peak radio luminosity comparable to that of SN 2006aj/GRB 060218 and SN 2010bh/GRB 100316D. Our radio observations of iPTF17cw imply a relativistically expanding outflow. However, further late-time observations with the VLA in its most extended configuration are needed to confirm fading of the iPTF17cw radio counterpart at all frequencies. X-ray observations carried out with Chandra reveal the presence of an X-ray counterpart with a luminosity similar to that of SN 2010bh/GRB 100316D. Searching the Fermi catalog for possible γ -rays reveals that GRB 161228B is spatially and temporally compatible with iPTF17cw. The similarity to SN 1998bw and SN 2009bb, the radio and X-ray detections, and the potential association with GRB 161228B all point to iPTF17cw being a new candidate member of the rare sample of optically discovered engine-driven BL-Ic SNe associated with relativistic ejecta.« less

  20. Planet Imager Discovers Young Kuiper Belt

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-07-01

    A debris disk just discovered around a nearby star is the closest thing yet seen to a young version of the Kuiper belt. This disk could be a key to better understanding the interactions between debris disks and planets, as well as how our solar system evolved early on in its lifetime. Hunting for an analog The best way to understand how the Kuiper belt — home to Pluto and thousands of other remnants of early icy planet formation in our solar system — developed would be to witness a similar debris disk in an earlier stage of its life. But before now, none of the disks we've discovered have been similar to our own: the rings are typically too large, the central star too massive, or the stars exist in regions very unlike what we think our Sun's birthplace was like. A collaboration led by Thayne Currie (National Astronomical Observatory of Japan) has changed this using the Gemini Planet Imager (GPI), part of a new generation of extreme adaptive-optics systems. The team discovered a debris disk of roughly the same size as the Kuiper belt orbiting the star HD 115600, located in the nearest OB association. The star is only slightly more massive than our Sun, and it lives in a star-forming region similar to the early Sun's environment. HD 115600 is different in one key way, however: it is only 15 million years old. This means that observing it gives us the perfect opportunity to observe how our solar system might have behaved when it was much younger. A promising future GPI's spatially-resolved spectroscopy, combined with measurements of the reflectivity of the disk, have led the team to suspect that the disk might be composed partly of water ice, just as the Kuiper belt is. The disk also shows evidence of having been sculpted by the motions of giant planets orbiting the central star, in much the same way as the outer planets of our solar system may have shaped the Kuiper belt. The observations of HD 115600 are some of the very first to emerge from GPI and the new

  1. Learning in settings with partial feedback and the wavy recency effect of rare events.

    PubMed

    Plonsky, Ori; Erev, Ido

    2017-03-01

    Analyses of human learning reveal a discrepancy between the long- and the short-term effects of outcomes on subsequent choice. The long-term effect is simple: favorable outcomes increase the choice rate of an alternative whereas unfavorable outcomes decrease it. The short-term effects are more complex. Favorable outcomes can decrease the choice rate of the best option. This pattern violates the positive recency assumption that underlies the popular models of learning. The current research tries to clarify the implications of these results. Analysis of wide sets of learning experiments shows that rare positive outcomes have a wavy recency effect. The probability of risky choice after a successful outcome from risk-taking at trial t is initially (at t+1) relatively high, falls to a minimum at t+2, then increases for about 15 trials, and then decreases again. Rare negative outcomes trigger a wavy reaction when the feedback is complete, but not under partial feedback. The difference between the effects of rare positive and rare negative outcomes and between full and partial feedback settings can be described as a reflection of an interaction of an effort to discover patterns with two other features of human learning: surprise-triggers-change and the hot stove effect. A similarity-based descriptive model is shown to capture well all these interacting phenomena. In addition, the model outperforms the leading models in capturing the outcomes of data used in the 2010 Technion Prediction Tournament. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. DISCOVER-AQ Acoustics : Measurement and Data Report.

    DOT National Transportation Integrated Search

    2015-09-01

    The following report documents the acoustic measurements that supplemented the September 2013 NASA DISCOVER-AQ flight tests in Houston, Texas and the corresponding data set developed from those measurements. These data include aircraft performance an...

  3. Next generation phenotyping using narrative reports in a rare disease clinical data warehouse.

    PubMed

    Garcelon, Nicolas; Neuraz, Antoine; Salomon, Rémi; Bahi-Buisson, Nadia; Amiel, Jeanne; Picard, Capucine; Mahlaoui, Nizar; Benoit, Vincent; Burgun, Anita; Rance, Bastien

    2018-05-31

    Secondary use of data collected in Electronic Health Records opens perspectives for increasing our knowledge of rare diseases. The clinical data warehouse (named Dr. Warehouse) at the Necker-Enfants Malades Children's Hospital contains data collected during normal care for thousands of patients. Dr. Warehouse is oriented toward the exploration of clinical narratives. In this study, we present our method to find phenotypes associated with diseases of interest. We leveraged the frequency and TF-IDF to explore the association between clinical phenotypes and rare diseases. We applied our method in six use cases: phenotypes associated with the Rett, Lowe, Silver Russell, Bardet-Biedl syndromes, DOCK8 deficiency and Activated PI3-kinase Delta Syndrome (APDS). We asked domain experts to evaluate the relevance of the top-50 (for frequency and TF-IDF) phenotypes identified by Dr. Warehouse and computed the average precision and mean average precision. Experts concluded that between 16 and 39 phenotypes could be considered as relevant in the top-50 phenotypes ranked by descending frequency discovered by Dr. Warehouse (resp. between 11 and 41 for TF-IDF). Average precision ranges from 0.55 to 0.91 for frequency and 0.52 to 0.95 for TF-IDF. Mean average precision was 0.79. Our study suggests that phenotypes identified in clinical narratives stored in Electronic Health Record can provide rare disease specialists with candidate phenotypes that can be used in addition to the literature. Clinical Data Warehouses can be used to perform Next Generation Phenotyping, especially in the context of rare diseases. We have developed a method to detect phenotypes associated with a group of patients using medical concepts extracted from free-text clinical narratives.

  4. Antibacterial, Anticancer and Neuroprotective Activities of Rare Actinobacteria from Mangrove Forest Soils.

    PubMed

    Azman, Adzzie-Shazleen; Othman, Iekhsan; Fang, Chee-Mun; Chan, Kok-Gan; Goh, Bey-Hing; Lee, Learn-Han

    2017-06-01

    Mangrove is a complex ecosystem that contains diverse microbial communities, including rare actinobacteria with great potential to produce bioactive compounds. To date, bioactive compounds extracted from mangrove rare actinobacteria have demonstrated diverse biological activities. The discovery of three novel rare actinobacteria by polyphasic approach, namely Microbacterium mangrovi MUSC 115 T , Sinomonas humi MUSC 117 T and Monashia flava MUSC 78 T from mangrove soils at Tanjung Lumpur, Peninsular Malaysia have led to the screening on antibacterial, anticancer and neuroprotective activities. A total of ten different panels of bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, ATCC 70069, Pseudomonas aeruginosa NRBC 112582 and others were selected for antibacterial screening. Three different neuroprotective models (hypoxia, oxidative stress, dementia) were done using SHSY5Y neuronal cells while two human cancer cells lines, namely human colon cancer cell lines (HT-29) and human cervical carcinoma cell lines (Ca Ski) were utilized for anticancer activity. The result revealed that all extracts exhibited bacteriostatic effects on the bacteria tested. On the other hand, the neuroprotective studies demonstrated M. mangrovi MUSC 115 T extract exhibited significant neuroprotective properties in oxidative stress and dementia model while the extract of strain M. flava MUSC 78 T was able to protect the SHSY5Y neuronal cells in hypoxia model. Furthermore, the extracts of M. mangrovi MUSC 115 T and M. flava MUSC 78 T exhibited anticancer effect against Ca Ski cell line. The chemical analysis of the extracts through GC-MS revealed that the majority of the compounds present in all extracts are heterocyclic organic compound that could explain for the observed bioactivities. Therefore, the results obtained in this study suggested that rare actinobacteria discovered from mangrove environment could be potential sources of antibacterial, anticancer and

  5. Discovering the Sequential Structure of Thought

    ERIC Educational Resources Information Center

    Anderson, John R.; Fincham, Jon M.

    2014-01-01

    Multi-voxel pattern recognition techniques combined with Hidden Markov models can be used to discover the mental states that people go through in performing a task. The combined method identifies both the mental states and how their durations vary with experimental conditions. We apply this method to a task where participants solve novel…

  6. The tremendous potential of deep-sea mud as a source of rare-earth elements.

    PubMed

    Takaya, Yutaro; Yasukawa, Kazutaka; Kawasaki, Takehiro; Fujinaga, Koichiro; Ohta, Junichiro; Usui, Yoichi; Nakamura, Kentaro; Kimura, Jun-Ichi; Chang, Qing; Hamada, Morihisa; Dodbiba, Gjergj; Nozaki, Tatsuo; Iijima, Koichi; Morisawa, Tomohiro; Kuwahara, Takuma; Ishida, Yasuyuki; Ichimura, Takao; Kitazume, Masaki; Fujita, Toyohisa; Kato, Yasuhiro

    2018-04-10

    Potential risks of supply shortages for critical metals including rare-earth elements and yttrium (REY) have spurred great interest in commercial mining of deep-sea mineral resources. Deep-sea mud containing over 5,000 ppm total REY content was discovered in the western North Pacific Ocean near Minamitorishima Island, Japan, in 2013. This REY-rich mud has great potential as a rare-earth metal resource because of the enormous amount available and its advantageous mineralogical features. Here, we estimated the resource amount in REY-rich mud with Geographical Information System software and established a mineral processing procedure to greatly enhance its economic value. The resource amount was estimated to be 1.2 Mt of rare-earth oxide for the most promising area (105 km 2  × 0-10 mbsf), which accounts for 62, 47, 32, and 56 years of annual global demand for Y, Eu, Tb, and Dy, respectively. Moreover, using a hydrocyclone separator enabled us to recover selectively biogenic calcium phosphate grains, which have high REY content (up to 22,000 ppm) and constitute the coarser domain in the grain-size distribution. The enormous resource amount and the effectiveness of the mineral processing are strong indicators that this new REY resource could be exploited in the near future.

  7. Discovering English with the Sketch Engine

    ERIC Educational Resources Information Center

    Thomas, James

    2014-01-01

    "Discovering English with the Sketch Engine" is the title of a new book (Thomas, 2014) which introduces the use of corpora in language study, teaching, writing and translating. It focuses on using the Sketch Engine to identify patterns of normal usage in many aspects of English ranging from morphology to discourse and pragmatics. This…

  8. A polygenic burden of rare disruptive mutations in schizophrenia

    PubMed Central

    Purcell, Shaun M.; Moran, Jennifer L.; Fromer, Menachem; Ruderfer, Douglas; Solovieff, Nadia; Roussos, Panos; O’Dushlaine, Colm; Chambert, Kimberly; Bergen, Sarah E.; Kähler, Anna; Duncan, Laramie; Stahl, Eli; Genovese, Giulio; Fernández, Esperanza; Collins, Mark O; Komiyama, Noboru H.; Choudhary, Jyoti S.; Magnusson, Patrik K. E.; Banks, Eric; Shakir, Khalid; Garimella, Kiran; Fennell, Tim; de Pristo, Mark; Grant, Seth G.N.; Haggarty, Stephen; Gabriel, Stacey; Scolnick, Edward M.; Lander, Eric S.; Hultman, Christina; Sullivan, Patrick F.; McCarroll, Steven A.; Sklar, Pamela

    2014-01-01

    By analyzing the exome sequences of 2,536 schizophrenia cases and 2,543 controls, we have demonstrated a polygenic burden primarily arising from rare (<1/10,000), disruptive mutations distributed across many genes. Especially enriched genesets included the voltage-gated calcium ion channel and the signaling complex formed by the activity-regulated cytoskeleton-associated (ARC) scaffold protein of the postsynaptic density (PSD), sets previously implicated by genome-wide association studies (GWAS) and copy-number variation (CNV) studies. Similar to reports in autism, targets of the fragile × mental retardation protein (FMRP, product of FMR1) were enriched for case mutations. No individual gene-based test achieved significance after correction for multiple testing and we did not detect any alleles of moderately low frequency (~0.5-1%) and moderately large effect. Taken together, these data suggest that population-based exome sequencing can discover risk alleles and complements established gene mapping paradigms in neuropsychiatric disease. PMID:24463508

  9. What if Fleming had not discovered penicillin?

    PubMed

    Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A; Chinnathambi, Arunachalam

    2014-09-01

    What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in medicine, such as organ transplantation, might have been delayed or, at best, made more hazardous. Penicillin might have come onto the scene a few years later but, had Fleming overlooked the discovery, it seems certain that penicillin would not have saved countless Allied lives, during and after D-Day. Instead of having enjoyed fifty and more years of the antibiotic age, it is argued here, that we would have had to rely upon highly developed sulphonamides, so-called "supasulfas", and other chemically-derived antibacterial drugs. Indeed, it might be the case that, even well into this new millennium, the antibiotic age has yet to dawn, and medicine is still waiting for someone to chance upon penicillin. Here we discuss what might have happened had Fleming not discovered penicillin and come to the conclusion that the medical armoury available today would have been far different and might have relied solely upon highly developed varieties of sulphonamides or similar, synthetic, non-antibiotic antibacterial agents.

  10. What if Fleming had not discovered penicillin?

    PubMed Central

    Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A.; Chinnathambi, Arunachalam

    2014-01-01

    What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in medicine, such as organ transplantation, might have been delayed or, at best, made more hazardous. Penicillin might have come onto the scene a few years later but, had Fleming overlooked the discovery, it seems certain that penicillin would not have saved countless Allied lives, during and after D-Day. Instead of having enjoyed fifty and more years of the antibiotic age, it is argued here, that we would have had to rely upon highly developed sulphonamides, so-called “supasulfas”, and other chemically-derived antibacterial drugs. Indeed, it might be the case that, even well into this new millennium, the antibiotic age has yet to dawn, and medicine is still waiting for someone to chance upon penicillin. Here we discuss what might have happened had Fleming not discovered penicillin and come to the conclusion that the medical armoury available today would have been far different and might have relied solely upon highly developed varieties of sulphonamides or similar, synthetic, non-antibiotic antibacterial agents. PMID:25183937

  11. The Universe for all to discover

    NASA Astrophysics Data System (ADS)

    Ortiz-Gil, A.; Ballesteros, F.; Espinós, H.; Fernández-Soto, A.; Lanzara, M.; Moya, M. J.; Navarro, J.

    2015-05-01

    In the title of this paper, we have changed the slogan of the International Year of Astronomy, ``The Universe yours to discover" to ``The Universe for all to discover" in order to emphasize the need to think about broader audiences when we plan astronomical activities at school or during outreach events. The strategy we propose follows what is known as the Universal Design for Learning (UDL). UDL allows to reach to the general public as well as to audiences which might be regarded as ``special" because they have some disability. It has been shown that everybody has a preferred style of learning (some remember better what they see, others what they hear or what they touch) and therefore, everybody is more or less able under the different styles of learning. Through this talk I am going to outline some of the principles of the UDL that can be applied in the teaching and communication of Astronomy, along with an example of its implementation in the project ``A Touch of the Universe".

  12. 31 CFR 501.723 - Prehearing disclosures; methods to discover additional matter.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... discover additional matter. 501.723 Section 501.723 Money and Finance: Treasury Regulations Relating to... disclosures; methods to discover additional matter. (a) Initial disclosures. (1) Except to the extent... the respondent); (ii) The legal theories upon which it will rely; (iii) Copies and a list of documents...

  13. 31 CFR 501.723 - Prehearing disclosures; methods to discover additional matter.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... discover additional matter. 501.723 Section 501.723 Money and Finance: Treasury Regulations Relating to... disclosures; methods to discover additional matter. (a) Initial disclosures. (1) Except to the extent... the respondent); (ii) The legal theories upon which it will rely; (iii) Copies and a list of documents...

  14. 31 CFR 501.723 - Prehearing disclosures; methods to discover additional matter.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... discover additional matter. 501.723 Section 501.723 Money and Finance: Treasury Regulations Relating to... disclosures; methods to discover additional matter. (a) Initial disclosures. (1) Except to the extent... the respondent); (ii) The legal theories upon which it will rely; (iii) Copies and a list of documents...

  15. 31 CFR 501.723 - Prehearing disclosures; methods to discover additional matter.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... discover additional matter. 501.723 Section 501.723 Money and Finance: Treasury Regulations Relating to... disclosures; methods to discover additional matter. (a) Initial disclosures. (1) Except to the extent... the respondent); (ii) The legal theories upon which it will rely; (iii) Copies and a list of documents...

  16. 48 CFR 752.209-71 - Organizational conflicts of interest discovered after award.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Interest Discovered After Award (JUN 1993) (a) The Contractor agrees that, if after award it discovers... make an immediate and full disclosure in writing to the Contracting Officer which shall include a...

  17. 48 CFR 752.209-71 - Organizational conflicts of interest discovered after award.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Interest Discovered After Award (JUN 1993) (a) The Contractor agrees that, if after award it discovers... make an immediate and full disclosure in writing to the Contracting Officer which shall include a...

  18. 48 CFR 752.209-71 - Organizational conflicts of interest discovered after award.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Interest Discovered After Award (JUN 1993) (a) The Contractor agrees that, if after award it discovers... make an immediate and full disclosure in writing to the Contracting Officer which shall include a...

  19. 48 CFR 752.209-71 - Organizational conflicts of interest discovered after award.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Interest Discovered After Award (JUN 1993) (a) The Contractor agrees that, if after award it discovers... make an immediate and full disclosure in writing to the Contracting Officer which shall include a...

  20. 48 CFR 752.209-71 - Organizational conflicts of interest discovered after award.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Interest Discovered After Award (JUN 1993) (a) The Contractor agrees that, if after award it discovers... make an immediate and full disclosure in writing to the Contracting Officer which shall include a...

  1. Einstein@Home discovers a radio-quiet gamma-ray millisecond pulsar.

    PubMed

    Clark, Colin J; Pletsch, Holger J; Wu, Jason; Guillemot, Lucas; Kerr, Matthew; Johnson, Tyrel J; Camilo, Fernando; Salvetti, David; Allen, Bruce; Anderson, David; Aulbert, Carsten; Beer, Christian; Bock, Oliver; Cuéllar, Andres; Eggenstein, Heinz-Bernd; Fehrmann, Henning; Kramer, Michael; Kwang, Shawn A; Machenschalk, Bernd; Nieder, Lars; Ackermann, Markus; Ajello, Marco; Baldini, Luca; Ballet, Jean; Barbiellini, Guido; Bastieri, Denis; Bellazzini, Ronaldo; Bissaldi, Elisabetta; Blandford, Roger D; Bloom, Elliott D; Bonino, Raffaella; Bottacini, Eugenio; Brandt, Terri J; Bregeon, Johan; Bruel, Philippe; Buehler, Rolf; Burnett, Toby H; Buson, Sara; Cameron, Rob A; Caputo, Regina; Caraveo, Patrizia A; Cavazzuti, Elisabetta; Cecchi, Claudia; Charles, Eric; Chekhtman, Alexandre; Ciprini, Stefano; Cominsky, Lynn R; Costantin, Denise; Cutini, Sara; D'Ammando, Filippo; De Luca, Andrea; Desiante, Rachele; Di Venere, Leonardo; Di Mauro, Mattia; Di Lalla, Niccolò; Digel, Seth W; Favuzzi, Cecilia; Ferrara, Elizabeth C; Franckowiak, Anna; Fukazawa, Yasushi; Funk, Stefan; Fusco, Piergiorgio; Gargano, Fabio; Gasparrini, Dario; Giglietto, Nico; Giordano, Francesco; Giroletti, Marcello; Gomez-Vargas, Germán A; Green, David; Grenier, Isabelle A; Guiriec, Sylvain; Harding, Alice K; Hewitt, John W; Horan, Deirdre; Jóhannesson, Guðlaugur; Kensei, Shiki; Kuss, Michael; La Mura, Giovanni; Larsson, Stefan; Latronico, Luca; Li, Jian; Longo, Francesco; Loparco, Francesco; Lovellette, Michael N; Lubrano, Pasquale; Magill, Jeffrey D; Maldera, Simone; Manfreda, Alberto; Mazziotta, Mario N; McEnery, Julie E; Michelson, Peter F; Mirabal, Nestor; Mitthumsiri, Warit; Mizuno, Tsunefumi; Monzani, Maria Elena; Morselli, Aldo; Moskalenko, Igor V; Nuss, Eric; Ohsugi, Takashi; Omodei, Nicola; Orienti, Monica; Orlando, Elena; Palatiello, Michele; Paliya, Vaidehi S; de Palma, Francesco; Paneque, David; Perkins, Jeremy S; Persic, Massimo; Pesce-Rollins, Melissa; Porter, Troy A; Principe, Giacomo; Rainò, Silvia; Rando, Riccardo; Ray, Paul S; Razzano, Massimiliano; Reimer, Anita; Reimer, Olaf; Romani, Roger W; Saz Parkinson, Pablo M; Sgrò, Carmelo; Siskind, Eric J; Smith, David A; Spada, Francesca; Spandre, Gloria; Spinelli, Paolo; Thayer, Jana B; Thompson, David J; Torres, Diego F; Troja, Eleonora; Vianello, Giacomo; Wood, Kent; Wood, Matthew

    2018-02-01

    Millisecond pulsars (MSPs) are old neutron stars that spin hundreds of times per second and appear to pulsate as their emission beams cross our line of sight. To date, radio pulsations have been detected from all rotation-powered MSPs. In an attempt to discover radio-quiet gamma-ray MSPs, we used the aggregated power from the computers of tens of thousands of volunteers participating in the Einstein@Home distributed computing project to search for pulsations from unidentified gamma-ray sources in Fermi Large Area Telescope data. This survey discovered two isolated MSPs, one of which is the only known rotation-powered MSP to remain undetected in radio observations. These gamma-ray MSPs were discovered in completely blind searches without prior constraints from other observations, raising hopes for detecting MSPs from a predicted Galactic bulge population.

  2. Discovering Science through Art-Based Activities

    ERIC Educational Resources Information Center

    Alberts, Rebecca

    2010-01-01

    Art and science are intrinsically linked; the essence of art and science is discovery. Both artists and scientists work in a systematic but creative way--knowledge and understanding are built up through pieces of art or a series of labs. In the classroom, integrating science and visual art can provide students with the latitude to think, discover,…

  3. The genus Nonomuraea: A review of a rare actinomycete taxon for novel metabolites.

    PubMed

    Sungthong, Rungroch; Nakaew, Nareeluk

    2015-05-01

    The genus Nonomuraea is a rare actinomycete taxon with a long taxonomic history, while its generic description was recently emended. The genus is less known among the rare actinomycete genera as its taxonomic position was revised several times. It can be found in diverse ecological niches, while most of its member species were isolated from soil samples. However, new trends to discover the genus in other habitats are increasing. Generic abundance of the genus was found to be dependent on geographical changes. Novel sources together with selective and invented isolation techniques might increase a chance to explore the genus and its novel candidates. Interestingly, some of its members have been revealed as a valuable source of novel metabolites for medical and industrial purposes. Broad-range of potent bioactive compounds including antimicrobial, anticancer, and antipsychotic substances, broad-spectrum antibiotics and biocatalysts can be synthesized by the genus. In order to investigate biosynthetic pathways of the bioactive compounds and self-resistant mechanisms to these compounds, the links from genes to metabolites have yet been needed for further discovery and biotechnological development of the genus Nonomuraea. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Candidiasis, A Rare Cause of Gastric Perforation: A Case Report and Review of Literature

    PubMed Central

    Ukekwe, FI; Nwajiobi, C; Agbo, MO; Ebede, SO; Eni, AO

    2015-01-01

    Fungi are unusually rare causes of gastric perforation, with most cases of gastric perforation occurring as complications of peptic ulcer disease (PUD), nonsteroidal anti-inflammatory drugs (NSAIDs) and gastric neoplasms. Here, we report the case of a 70-year-old Nigerian male who presented with severe epigastric pain, with no associated history of PUD, NSAIDs use or gastric neoplasm. An emergency exploratory laparotomy was performed and a gastric perforation was discovered and repaired. Histopathological examination of the gastric perforation edge biopsy revealed an intense Candida growth consisting of numerous fungal spores and hyphae invading and destroying the gastric wall. He was subsequently treated with fluconazole antifungal and discharged home after an uneventful postoperative period. PMID:26229723

  5. Candidiasis, A Rare Cause of Gastric Perforation: A Case Report and Review of Literature.

    PubMed

    Ukekwe, F I; Nwajiobi, C; Agbo, M O; Ebede, S O; Eni, A O

    2015-01-01

    Fungi are unusually rare causes of gastric perforation, with most cases of gastric perforation occurring as complications of peptic ulcer disease (PUD), nonsteroidal anti-inflammatory drugs (NSAIDs) and gastric neoplasms. Here, we report the case of a 70-year-old Nigerian male who presented with severe epigastric pain, with no associated history of PUD, NSAIDs use or gastric neoplasm. An emergency exploratory laparotomy was performed and a gastric perforation was discovered and repaired. Histopathological examination of the gastric perforation edge biopsy revealed an intense Candida growth consisting of numerous fungal spores and hyphae invading and destroying the gastric wall. He was subsequently treated with fluconazole antifungal and discharged home after an uneventful postoperative period.

  6. How cosmic rays were discovered and why they received this misnomer

    NASA Astrophysics Data System (ADS)

    Dorman, I. V.; Dorman, L. I.

    2014-05-01

    As many great discoveries, the phenomenon of cosmic rays was discovered mainly accidentally, during investigations that sought to answer another question: what are sources of air ionization? This problem became interesting for science about 230 years ago in the end of the 18th century, when physics met with a problem of leakage of electrical charge from very good isolated bodies. We describe the history how step by step cosmic rays was discovered and why this phenomenon received misnomer, how in cosmic rays was discovered the first antiparticle - positron. These discoveries were recognized among greatest in the 20th Century and were awarded by Nobel Prize.

  7. Discovering Synergistic Drug Combination from a Computational Perspective.

    PubMed

    Ding, Pingjian; Luo, Jiawei; Liang, Cheng; Xiao, Qiu; Cao, Buwen; Li, Guanghui

    2018-03-30

    Synergistic drug combinations play an important role in the treatment of complex diseases. The identification of effective drug combination is vital to further reduce the side effects and improve therapeutic efficiency. In previous years, in vitro method has been the main route to discover synergistic drug combinations. However, many limitations of time and resource consumption lie within the in vitro method. Therefore, with the rapid development of computational models and the explosive growth of large and phenotypic data, computational methods for discovering synergistic drug combinations are an efficient and promising tool and contribute to precision medicine. It is the key of computational methods how to construct the computational model. Different computational strategies generate different performance. In this review, the recent advancements in computational methods for predicting effective drug combination are concluded from multiple aspects. First, various datasets utilized to discover synergistic drug combinations are summarized. Second, we discussed feature-based approaches and partitioned these methods into two classes including feature-based methods in terms of similarity measure, and feature-based methods in terms of machine learning. Third, we discussed network-based approaches for uncovering synergistic drug combinations. Finally, we analyzed and prospected computational methods for predicting effective drug combinations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Intramuscular Lipoma of the Thenar: A Rare Case

    PubMed Central

    Papakostas, Theodoros; Tsovilis, Aristomenis E.; Pakos, Emilios E.

    2016-01-01

    Lipomas are the most common benign mesenchymal tumors. They are located either subcutaneously or under the investing fascia in intramuscular or intermuscular regions. The reported frequency of intramuscular lipomas among all benign adipocytic tumors is 1.0%–5.0% and for intermuscular lipomas is 0.3%–1.9%. The frequency of these lesions is the same in all age groups, but in adults deep seated-lipomas are most commonly discovered between the ages of 30 and 60. The most common sites of involvement of intramuscular lipomas are the large muscles of the extremities, especially those of the thigh, shoulder, and upper arm. Intramuscular lipomas of the hand are extremely rare and only few cases have been reported in the literature. In cases with hand location, they may present with functional deficit or neurovascular compromise due to the effect of the mass. We report an unusual case of a large intramuscular lipoma of the thenar that was treated with surgical excision due to the impairment of hand function. PMID:26894225

  9. China's rare-earth industry

    USGS Publications Warehouse

    Tse, Pui-Kwan

    2011-01-01

    Introduction China's dominant position as the producer of over 95 percent of the world output of rare-earth minerals and rapid increases in the consumption of rare earths owing to the emergence of new clean-energy and defense-related technologies, combined with China's decisions to restrict exports of rare earths, have resulted in heightened concerns about the future availability of rare earths. As a result, industrial countries such as Japan, the United States, and countries of the European Union face tighter supplies and higher prices for rare earths. This paper briefly reviews China's rare-earth production, consumption, and reserves and the important policies and regulations regarding the production and trade of rare earths, including recently announced export quotas. The 15 lanthanide elements-lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium (atomic numbers 57-71)-were originally known as the rare earths from their occurrence in oxides mixtures. Recently, some researchers have included two other elements-scandium and yttrium-in their discussion of rare earths. Yttrium (atomic number 39), which lies above lanthanum in transition group III of the periodic table and has a similar 3+ ion with a noble gas core, has both atomic and ionic radii similar in size to those of terbium and dysprosium and is generally found in nature with lanthanides. Scandium (atomic number 21) has a smaller ionic radius than yttrium and the lanthanides, and its chemical behavior is intermediate between that of aluminum and the lanthanides. It is found in nature with the lanthanides and yttrium. Rare earths are used widely in high-technology and clean-energy products because they impart special properties of magnetism, luminescence, and strength. Rare earths are also used in weapon systems to obtain the same properties.

  10. Einstein@Home discovers a radio-quiet gamma-ray millisecond pulsar

    DOE PAGES

    Clark, Colin J.; Pletsch, Holger J.; Wu, Jason; ...

    2018-02-28

    Millisecond pulsars (MSPs) are old neutron stars that spin hundreds of times per second and appear to pulsate as their emission beams cross our line of sight. To date, radio pulsations have been detected from all rotation-powered MSPs. Here, in an attempt to discover radio-quiet gamma-ray MSPs, we used the aggregated power from the computers of tens of thousands of volunteers participating in the Einstein@Home distributed computing project to search for pulsations from unidentified gamma-ray sources in Fermi Large Area Telescope data. This survey discovered two isolated MSPs, one of which is the only known rotation-powered MSP to remain undetectedmore » in radio observations. These gamma-ray MSPs were discovered in completely blind searches without prior constraints from other observations, raising hopes for detecting MSPs from a predicted Galactic bulge population.« less

  11. Einstein@Home discovers a radio-quiet gamma-ray millisecond pulsar

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

    Clark, Colin J.; Pletsch, Holger J.; Wu, Jason

    Millisecond pulsars (MSPs) are old neutron stars that spin hundreds of times per second and appear to pulsate as their emission beams cross our line of sight. To date, radio pulsations have been detected from all rotation-powered MSPs. Here, in an attempt to discover radio-quiet gamma-ray MSPs, we used the aggregated power from the computers of tens of thousands of volunteers participating in the Einstein@Home distributed computing project to search for pulsations from unidentified gamma-ray sources in Fermi Large Area Telescope data. This survey discovered two isolated MSPs, one of which is the only known rotation-powered MSP to remain undetectedmore » in radio observations. These gamma-ray MSPs were discovered in completely blind searches without prior constraints from other observations, raising hopes for detecting MSPs from a predicted Galactic bulge population.« less

  12. Einstein@Home discovers a radio-quiet gamma-ray millisecond pulsar

    PubMed Central

    Clark, Colin J.; Pletsch, Holger J.; Wu, Jason; Guillemot, Lucas; Kerr, Matthew; Johnson, Tyrel J.; Camilo, Fernando; Salvetti, David; Allen, Bruce; Anderson, David; Aulbert, Carsten; Beer, Christian; Bock, Oliver; Cuéllar, Andres; Eggenstein, Heinz-Bernd; Fehrmann, Henning; Kramer, Michael; Kwang, Shawn A.; Machenschalk, Bernd; Nieder, Lars; Ackermann, Markus; Ajello, Marco; Baldini, Luca; Ballet, Jean; Barbiellini, Guido; Bastieri, Denis; Bellazzini, Ronaldo; Bissaldi, Elisabetta; Blandford, Roger D.; Bloom, Elliott D.; Bonino, Raffaella; Bottacini, Eugenio; Brandt, Terri J.; Bregeon, Johan; Bruel, Philippe; Buehler, Rolf; Burnett, Toby H.; Buson, Sara; Cameron, Rob A.; Caputo, Regina; Caraveo, Patrizia A.; Cavazzuti, Elisabetta; Cecchi, Claudia; Charles, Eric; Chekhtman, Alexandre; Ciprini, Stefano; Cominsky, Lynn R.; Costantin, Denise; Cutini, Sara; D’Ammando, Filippo; De Luca, Andrea; Desiante, Rachele; Di Venere, Leonardo; Di Mauro, Mattia; Di Lalla, Niccolò; Digel, Seth W.; Favuzzi, Cecilia; Ferrara, Elizabeth C.; Franckowiak, Anna; Fukazawa, Yasushi; Funk, Stefan; Fusco, Piergiorgio; Gargano, Fabio; Gasparrini, Dario; Giglietto, Nico; Giordano, Francesco; Giroletti, Marcello; Gomez-Vargas, Germán A.; Green, David; Grenier, Isabelle A.; Guiriec, Sylvain; Harding, Alice K.; Hewitt, John W.; Horan, Deirdre; Jóhannesson, Guðlaugur; Kensei, Shiki; Kuss, Michael; La Mura, Giovanni; Larsson, Stefan; Latronico, Luca; Li, Jian; Longo, Francesco; Loparco, Francesco; Lovellette, Michael N.; Lubrano, Pasquale; Magill, Jeffrey D.; Maldera, Simone; Manfreda, Alberto; Mazziotta, Mario N.; McEnery, Julie E.; Michelson, Peter F.; Mirabal, Nestor; Mitthumsiri, Warit; Mizuno, Tsunefumi; Monzani, Maria Elena; Morselli, Aldo; Moskalenko, Igor V.; Nuss, Eric; Ohsugi, Takashi; Omodei, Nicola; Orienti, Monica; Orlando, Elena; Palatiello, Michele; Paliya, Vaidehi S.; de Palma, Francesco; Paneque, David; Perkins, Jeremy S.; Persic, Massimo; Pesce-Rollins, Melissa; Porter, Troy A.; Principe, Giacomo; Rainò, Silvia; Rando, Riccardo; Ray, Paul S.; Razzano, Massimiliano; Reimer, Anita; Reimer, Olaf; Romani, Roger W.; Saz Parkinson, Pablo M.; Sgrò, Carmelo; Siskind, Eric J.; Smith, David A.; Spada, Francesca; Spandre, Gloria; Spinelli, Paolo; Thayer, Jana B.; Thompson, David J.; Torres, Diego F.; Troja, Eleonora; Vianello, Giacomo; Wood, Kent; Wood, Matthew

    2018-01-01

    Millisecond pulsars (MSPs) are old neutron stars that spin hundreds of times per second and appear to pulsate as their emission beams cross our line of sight. To date, radio pulsations have been detected from all rotation-powered MSPs. In an attempt to discover radio-quiet gamma-ray MSPs, we used the aggregated power from the computers of tens of thousands of volunteers participating in the Einstein@Home distributed computing project to search for pulsations from unidentified gamma-ray sources in Fermi Large Area Telescope data. This survey discovered two isolated MSPs, one of which is the only known rotation-powered MSP to remain undetected in radio observations. These gamma-ray MSPs were discovered in completely blind searches without prior constraints from other observations, raising hopes for detecting MSPs from a predicted Galactic bulge population. PMID:29503868

  13. Quantifying rare, deleterious variation in 12 human cytochrome P450 drug-metabolism genes in a large-scale exome dataset.

    PubMed

    Gordon, Adam S; Tabor, Holly K; Johnson, Andrew D; Snively, Beverly M; Assimes, Themistocles L; Auer, Paul L; Ioannidis, John P A; Peters, Ulrike; Robinson, Jennifer G; Sucheston, Lara E; Wang, Danxin; Sotoodehnia, Nona; Rotter, Jerome I; Psaty, Bruce M; Jackson, Rebecca D; Herrington, David M; O'Donnell, Christopher J; Reiner, Alexander P; Rich, Stephen S; Rieder, Mark J; Bamshad, Michael J; Nickerson, Deborah A

    2014-04-15

    The study of genetic influences on drug response and efficacy ('pharmacogenetics') has existed for over 50 years. Yet, we still lack a complete picture of how genetic variation, both common and rare, affects each individual's responses to medications. Exome sequencing is a promising alternative method for pharmacogenetic discovery as it provides information on both common and rare variation in large numbers of individuals. Using exome data from 2203 AA and 4300 Caucasian individuals through the NHLBI Exome Sequencing Project, we conducted a survey of coding variation within 12 Cytochrome P450 (CYP) genes that are collectively responsible for catalyzing nearly 75% of all known Phase I drug oxidation reactions. In addition to identifying many polymorphisms with known pharmacogenetic effects, we discovered over 730 novel nonsynonymous alleles across the 12 CYP genes of interest. These alleles include many with diverse functional effects such as premature stop codons, aberrant splicesites and mutations at conserved active site residues. Our analysis considering both novel, predicted functional alleles as well as known, actionable CYP alleles reveals that rare, deleterious variation contributes markedly to the overall burden of pharmacogenetic alleles within the populations considered, and that the contribution of rare variation to this burden is over three times greater in AA individuals as compared with Caucasians. While most of these impactful alleles are individually rare, 7.6-11.7% of individuals interrogated in the study carry at least one newly described potentially deleterious alleles in a major drug-metabolizing CYP.

  14. The Not-So-Rare Earths.

    ERIC Educational Resources Information Center

    Muecke, Gunter K.; Moller, Peter

    1988-01-01

    Describes the characteristics of rare earth elements. Details the physical chemistry of rare earths. Reviews the history of rare earth chemistry and mineralogy. Discusses the mineralogy and crystallography of the formation of rare earth laden minerals found in the earth's crust. Characterizes the geologic history of rare earth elements. (CW)

  15. Mining with Rare Cases

    NASA Astrophysics Data System (ADS)

    Weiss, Gary M.

    Rare cases are often the most interesting cases. For example, in medical diagnosis one is typically interested in identifying relatively rare diseases, such as cancer, rather than more frequently occurring ones, such as the common cold. In this chapter we discuss the role of rare cases in Data Mining. Specific problems associated with mining rare cases are discussed, followed by a description of methods for addressing these problems.

  16. Rare cancers: Challenges & issues.

    PubMed

    Pillai, Raveendran K; Jayasree, K

    2017-01-01

    Rare cancers account for about 22 per cent of all cancers diagnosed worldwide, disproportionately affecting some demographic groups, with an occurrence of less than 6 per 100,000 individuals annually. Many rare cancers in adults, adolescents and children are not curable, and patients and care providers have little option to take therapeutic decisions. The epidemiology of rare cancers is a challenging area of study but is inadequately addressed. Despite efforts mainly in some European nations, a few improvements have been observed in the management of rare cancers. Reasons for this obvious stagnation are multifactorial and are mainly inherent to logistical difficulties in carrying out clinical trials in very small patient populations, hesitation of the pharmaceutical industry to spend in small markets and complexity in creating adequate information for the development of cost-effective drugs. Rare cancers also face specific challenges that include late and incorrect diagnosis, lack of clinical expertise and lack of research interest and development of new therapies. The utilization of nationally representative study findings for the patients' evaluation may possibly offer chances to find out pathogenesis and prevalence, and this will eventually lead to control and prevention. Currently, advancing targeted therapies offer a great opportunity for the better management of rare cancers. Conducting clinical trials with small patient population, innovative clinical trial approach, prevailing controlling obstacles for international cooperation and financial support for research are the present challenges for rare cancers. The International Rare Cancers Initiative functions as a main platform for achieving new international clinical trials in rare tumours. This review delineates the current challenges and issues in the interpretation, management and research scenarios of rare cancers.

  17. Rare cancers: Challenges & issues

    PubMed Central

    Pillai, Raveendran K.; Jayasree, K.

    2017-01-01

    Rare cancers account for about 22 per cent of all cancers diagnosed worldwide, disproportionately affecting some demographic groups, with an occurrence of less than 6 per 100,000 individuals annually. Many rare cancers in adults, adolescents and children are not curable, and patients and care providers have little option to take therapeutic decisions. The epidemiology of rare cancers is a challenging area of study but is inadequately addressed. Despite efforts mainly in some European nations, a few improvements have been observed in the management of rare cancers. Reasons for this obvious stagnation are multifactorial and are mainly inherent to logistical difficulties in carrying out clinical trials in very small patient populations, hesitation of the pharmaceutical industry to spend in small markets and complexity in creating adequate information for the development of cost-effective drugs. Rare cancers also face specific challenges that include late and incorrect diagnosis, lack of clinical expertise and lack of research interest and development of new therapies. The utilization of nationally representative study findings for the patients’ evaluation may possibly offer chances to find out pathogenesis and prevalence, and this will eventually lead to control and prevention. Currently, advancing targeted therapies offer a great opportunity for the better management of rare cancers. Conducting clinical trials with small patient population, innovative clinical trial approach, prevailing controlling obstacles for international cooperation and financial support for research are the present challenges for rare cancers. The International Rare Cancers Initiative functions as a main platform for achieving new international clinical trials in rare tumours. This review delineates the current challenges and issues in the interpretation, management and research scenarios of rare cancers. PMID:28574010

  18. Hydrothermal vent fields discovered in the southern Gulf of California clarify role of habitat in augmenting regional diversity

    PubMed Central

    Johnson, Shannon; Tunnicliffe, Verena; Caress, David; Clague, David; Escobar, Elva; Lundsten, Lonny; Paduan, Jennifer B.; Rouse, Greg; Salcedo, Diana L.; Soto, Luis A.; Zierenberg, Robert; Vrijenhoek, Robert

    2017-01-01

    Hydrothermal vent communities are distributed along mid-ocean spreading ridges as isolated patches. While distance is a key factor influencing connectivity among sites, habitat characteristics are also critical. The Pescadero Basin (PB) and Alarcón Rise (AR) vent fields, recently discovered in the southern Gulf of California, are bounded by previously known vent localities (e.g. Guaymas Basin and 21° N East Pacific Rise); yet, the newly discovered vents differ markedly in substrata and vent fluid attributes. Out of 116 macrofaunal species observed or collected, only three species are shared among all four vent fields, while 73 occur at only one locality. Foundation species at basalt-hosted sulfide chimneys on the AR differ from the functional equivalents inhabiting sediment-hosted carbonate chimneys in the PB, only 75 km away. The dominant species of symbiont-hosting tubeworms and clams, and peripheral suspension-feeding taxa, differ between the sites. Notably, the PB vents host a limited and specialized fauna in which 17 of 26 species are unknown at other regional vents and many are new species. Rare sightings and captured larvae of the ‘missing’ species revealed that dispersal limitation is not responsible for differences in community composition at the neighbouring vent localities. Instead, larval recruitment-limiting habitat suitability probably favours species differentially. As scenarios develop to design conservation strategies around mining of seafloor sulfide deposits, these results illustrate that models encompassing habitat characteristics are needed to predict metacommunity structure. PMID:28724734

  19. Hydrothermal vent fields discovered in the southern Gulf of California clarify role of habitat in augmenting regional diversity.

    PubMed

    Goffredi, Shana K; Johnson, Shannon; Tunnicliffe, Verena; Caress, David; Clague, David; Escobar, Elva; Lundsten, Lonny; Paduan, Jennifer B; Rouse, Greg; Salcedo, Diana L; Soto, Luis A; Spelz-Madero, Ronald; Zierenberg, Robert; Vrijenhoek, Robert

    2017-07-26

    Hydrothermal vent communities are distributed along mid-ocean spreading ridges as isolated patches. While distance is a key factor influencing connectivity among sites, habitat characteristics are also critical. The Pescadero Basin (PB) and Alarcón Rise (AR) vent fields, recently discovered in the southern Gulf of California, are bounded by previously known vent localities (e.g. Guaymas Basin and 21° N East Pacific Rise); yet, the newly discovered vents differ markedly in substrata and vent fluid attributes. Out of 116 macrofaunal species observed or collected, only three species are shared among all four vent fields, while 73 occur at only one locality. Foundation species at basalt-hosted sulfide chimneys on the AR differ from the functional equivalents inhabiting sediment-hosted carbonate chimneys in the PB, only 75 km away. The dominant species of symbiont-hosting tubeworms and clams, and peripheral suspension-feeding taxa, differ between the sites. Notably, the PB vents host a limited and specialized fauna in which 17 of 26 species are unknown at other regional vents and many are new species. Rare sightings and captured larvae of the 'missing' species revealed that dispersal limitation is not responsible for differences in community composition at the neighbouring vent localities. Instead, larval recruitment-limiting habitat suitability probably favours species differentially. As scenarios develop to design conservation strategies around mining of seafloor sulfide deposits, these results illustrate that models encompassing habitat characteristics are needed to predict metacommunity structure. © 2017 The Authors.

  20. Strontium-90 Error Discovered in Subcontract Laboratory Spreadsheet

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

    D. D. Brown A. S. Nagel

    1999-07-31

    West Valley Demonstration Project health physicists and environment scientists discovered a series of errors in a subcontractor's spreadsheet being used to reduce data as part of their strontium-90 analytical process.

  1. Intellectual Development and Interaction Effectiveness with DISCOVER.

    ERIC Educational Resources Information Center

    Roselle, Bruce E.; Hummel, Thomas J.

    1988-01-01

    Used Knefelkamp's and Slepitza's (1976) model of career-related intellectual development to investigate how students at different levels of development think as they interact with a computer-assisted career guidance system, DISCOVER II, which comprises modules on understanding interests, values, and abilities; searching for occupations based on…

  2. Pseudomonas blight discovered on raspberry in Watsonville

    USDA-ARS?s Scientific Manuscript database

    In the winter (February) of 2013, a field of raspberries in Watsonville was discovered to be infected with Pseudomonas syringae, the causal agent of Pseudomonas blight disease. This was the first documentation of this disease on raspberry in our region. The infection of raspberry plants is manifeste...

  3. Discovering Structural Regularity in 3D Geometry

    PubMed Central

    Pauly, Mark; Mitra, Niloy J.; Wallner, Johannes; Pottmann, Helmut; Guibas, Leonidas J.

    2010-01-01

    We introduce a computational framework for discovering regular or repeated geometric structures in 3D shapes. We describe and classify possible regular structures and present an effective algorithm for detecting such repeated geometric patterns in point- or mesh-based models. Our method assumes no prior knowledge of the geometry or spatial location of the individual elements that define the pattern. Structure discovery is made possible by a careful analysis of pairwise similarity transformations that reveals prominent lattice structures in a suitable model of transformation space. We introduce an optimization method for detecting such uniform grids specifically designed to deal with outliers and missing elements. This yields a robust algorithm that successfully discovers complex regular structures amidst clutter, noise, and missing geometry. The accuracy of the extracted generating transformations is further improved using a novel simultaneous registration method in the spatial domain. We demonstrate the effectiveness of our algorithm on a variety of examples and show applications to compression, model repair, and geometry synthesis. PMID:21170292

  4. Magneto-structural correlations in rare-earth cobalt pnictides

    NASA Astrophysics Data System (ADS)

    Thompson, Corey Mitchell

    Magnetic materials are used in many applications such as credit cards, hard drives, electric motors, sensors, etc. Although a vast range of magnetic solids is available for these purposes, our ability to improve their efficiency and discover new materials remains paramount to the sustainable progress and economic profitability in many technological areas. The search for magnetic solids with improved performance requires fundamental understanding of correlations between the structural, electronic, and magnetic properties of existing materials, as well as active exploratory synthesis that targets the development of new magnets. Some of the strongest permanent magnets, Nd 2Fe14B, SmCo5, and Sm2Co17, combine transition and rare-earth metals, benefiting from the strong exchange between the 4f and 3d magnetic sublattices. Although these materials have been studied in great detail, the development of novel magnets requires thorough investigation of other 3d-4 f intermetallics, in order to gain further insights into correlations between their crystal structures and magnetic properties. Among many types of intermetallic materials, ternary pnictides RCo 2Pn2 (R = La, Ce, Pr, Nd; Pn = P, As) are of interest because, despite their simple crystal structures, they contain two magnetic sublattices, exchange interactions between which may lead to rich and unprecedented magnetic behavior. Nevertheless, magnetism of these materials was studied only to a limited extent, especially as compared to the extensive studies of their silicide and germanide analogues. The ThCr2Si2 structure type, to which these ternary pnictides belong, is one of the most ubiquitous atomic arrangements encountered among intermetallic compounds. It accounts for over 1000 known intermetallics and has received increased attention due to the recently discovered FeAs-based superconductors. This dissertation is devoted to the investigation of

  5. Uncloaking a cryptic, threatened rail with molecular markers: origins, connectivity and demography of a recently-discovered population

    USGS Publications Warehouse

    Girard, Philippe; Takekawa, John Y.; Beissinger, Steven R.

    2010-01-01

    The threatened California Black Rail lives under dense marsh vegetation, is rarely observed, flies weakly and has a highly disjunct distribution. The largest population of rails is found in 8–10 large wetlands in San Francisco Bay (SF Bay), but a population was recently discovered in the foothills of the Sierra Nevada Mountains (Foothills), within a wetland network comprised of over 200 small marshes. Using microsatellite and mitochondrial analyses, our objectives were to determine the origins, connectivity and demography of this recently-discovered population. Analyses of individuals from the Foothills (n = 31), SF Bay (n = 31), the Imperial Valley (n = 6) and the East Coast (n = 3), combined with rigorous power evaluations, provided valuable insights into past history and current dynamics of the species in Northern California that challenge conventional wisdom about the species. The Foothills and SF Bay populations have diverged strongly from the Imperial Valley population, even more strongly than from individuals of the East Coast subspecies. The data also suggest a historical presence of the species in the Foothills. The SF Bay and Foothills populations had similar estimated effective population size over the areas sampled and appeared linked by a strongly asymmetrical migration pattern, with a greater probability of movement from the Foothills to SF Bay than vice versa. Random mating was inferred in the Foothills, but local substructure among marshes and inbreeding were detected in SF Bay, suggesting different dispersal patterns within each location. The unexpected dimensions of Black Rail demography and population structure suggested by these analyses and their potential importance for management are discussed.

  6. Advanced Cell Classifier: User-Friendly Machine-Learning-Based Software for Discovering Phenotypes in High-Content Imaging Data.

    PubMed

    Piccinini, Filippo; Balassa, Tamas; Szkalisity, Abel; Molnar, Csaba; Paavolainen, Lassi; Kujala, Kaisa; Buzas, Krisztina; Sarazova, Marie; Pietiainen, Vilja; Kutay, Ulrike; Smith, Kevin; Horvath, Peter

    2017-06-28

    High-content, imaging-based screens now routinely generate data on a scale that precludes manual verification and interrogation. Software applying machine learning has become an essential tool to automate analysis, but these methods require annotated examples to learn from. Efficiently exploring large datasets to find relevant examples remains a challenging bottleneck. Here, we present Advanced Cell Classifier (ACC), a graphical software package for phenotypic analysis that addresses these difficulties. ACC applies machine-learning and image-analysis methods to high-content data generated by large-scale, cell-based experiments. It features methods to mine microscopic image data, discover new phenotypes, and improve recognition performance. We demonstrate that these features substantially expedite the training process, successfully uncover rare phenotypes, and improve the accuracy of the analysis. ACC is extensively documented, designed to be user-friendly for researchers without machine-learning expertise, and distributed as a free open-source tool at www.cellclassifier.org. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. [Rare bile duct anatomy variant - Right bile duct intraparenchymal junction into the left bile duct].

    PubMed

    Gál, Adrián Róbert; Kalmár-Nagy, Károly; Fincsur, András; Horváth, Örs Péter; Vereczkei, András

    2018-03-01

    The authors present a case of a 67-year-old male patient, who previously had been diagnosed with a malignant liver tumor localized in segment II. He underwent bisegmentectomy (II and III) and partial IV segmentectomy. After the primary surgery jaundice developed, the level of bilirubin increased and after several imaging modalities reoperation was indicated. During the surgery a rare bile duct anatomy variant was found. The right hepatic duct joined the left duct in the parenchyma of the left lobe, and was ligated at the resection. As the liver hilum was not explored, the absence of the right duct was not discovered. Reconstruction of the biliary system was accomplished by a Roux-en-Y loop.

  8. [Application of multiplex PCR for the screening of genotyping system for the rare blood groups Fy(a-), s-,k-,Di(b-) and Js(b-)].

    PubMed

    Jiao, Wei; Xie, Li; Li, Hailan; Lan, Jiao; Mo, Zhuning; Yang, Ziji; Liu, Fei; Xiao, Ruiping; He, Yunlei; Ye, Luyi; Zhu, Ziyan

    2014-04-01

    To screen rare blood groups Fy(a-), s-, k-, Di(b-) and Js(b-) in an ethnic Zhuang population. Sequence-specific primers were designed based on single nucleotide polymorphism (SNP) sites of blood group antigens Fy(b) and s. A specific multiplex PCR system I was established. Multiplex PCR system II was applied to detect alleles antigens Di(b), k, Js(b)1910 and Js(b) 2019 at the same time. The two systems was were used to screen for rare blood group antigens in 4490 randomly selected healthy donors of Guangxi Zhuang ethnic origin. We successfully made the multiplex PCR system I. We detected the rare blood group antigens using the two PCR system. There are five Fy(a-), three s(-), two Di(b-) in 4490 Guangxi zhuang random samples. The multiplex PCR system I has achieved good accuracy and stability. With multiplex PCR systems I and II, 4490 samples were screened. Five Fy(a-), three s(-) and two Di(b-) samples were discovered. Multiplex PCR is an effective methods, which can be used for high throughput screening of rare blood groups. The rare blood types of Guangxi Zhuang ethnic origin obtained through the screening can provide valuable information for compatible blood transfusion. Through screening we obtained precious rare blood type materials which can be used to improve the capability of compatible infusion and reduce the transfusion reactions.

  9. Discovering Astronomy: An Astro 101 e-book

    NASA Astrophysics Data System (ADS)

    Shawl, Stephen J.; Byrd, Gene; Deustua, Susana E.; LoPresto, Michael C.

    2016-01-01

    Discovering Astronomy, now available in its 6th edition as an eText, has many advantages and features for your students. We have partnered with etextink.com and WebAssign.net to produce an affordable set of cost-saving options for your students. Also available is the Discovering Astronomy Activity Manual, which provides students with an active-learning experience.Our etext is device independent and thus accessible through any web browser. Americans with Disabilities Act compatibility provides access for all students. Hotlinks to outside sites provide further information for interested students. Lecture demonstration videos of important concepts, made specifically for this new edition, are embedded within the text as appropriate. Students can highlight text, take notes, and bookmark locations within the text. Important terms are linked to the glossary. Search capabilities allow students to easily find what they want.Instructors can interact with their students directly through the etext once the class roster has been provided. For example, instructors can embed assignments into their students' etext and add their own notes and updates, which are immediately visible to their students.Updates can be quickly made by us as new findings become available. For example, updates from New Horizons were added at the time of the closest approach to Pluto, and an update on the recent announcement of current water on Mars was added the day of the announcement.We will present results of our own experience with college and high school students' use of Discovering Astronomy in online courses.Details of the book, a sample chapter, and other information are available at discoveringastronomy.weebly.com.

  10. DISCOVER AQ Research Plane Arrives

    NASA Image and Video Library

    2011-06-28

    An unidentified researcher works aboard the P-3B NASA research aircraft at Baltimore/Washington International Thurgood Marshall Airport, Tuesday, June 28, 2011, in Baltimore, Md. The aircraft is part of a month-long field campaign designed to improve satellite measurements of air pollution. The name of the experiment -- Deriving Information on Surface conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER -- AQ) -- is a mouthful, but its purpose is simple. Come July, the aircraft will be flying spirals over six ground stations in Maryland. Photo Credit: (NASA/Paul E. Alers)

  11. Cochlear Implants Keep Twin Sisters Learning, Discovering Together

    MedlinePlus

    ... University. Photo: Johns Hopkins University Keep Twin Sisters Learning, Discovering Together Mia and Isabelle Jeppsen, 10, share ... her mother, gratefully, "There's the obvious benefit of learning to read, write and communicate with facility and ...

  12. A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans.

    PubMed

    Timpson, Nicholas J; Walter, Klaudia; Min, Josine L; Tachmazidou, Ioanna; Malerba, Giovanni; Shin, So-Youn; Chen, Lu; Futema, Marta; Southam, Lorraine; Iotchkova, Valentina; Cocca, Massimiliano; Huang, Jie; Memari, Yasin; McCarthy, Shane; Danecek, Petr; Muddyman, Dawn; Mangino, Massimo; Menni, Cristina; Perry, John R B; Ring, Susan M; Gaye, Amadou; Dedoussis, George; Farmaki, Aliki-Eleni; Burton, Paul; Talmud, Philippa J; Gambaro, Giovanni; Spector, Tim D; Smith, George Davey; Durbin, Richard; Richards, J Brent; Humphries, Steve E; Zeggini, Eleftheria; Soranzo, Nicole

    2014-09-16

    The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (-1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10(-8))) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (-1.0 s.d. (s.e.=0.173), P-value=7.32 × 10(-9)). This is consistent with an effect between 0.5 and 1.5 mmol l(-1) dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale.

  13. Discovering amino acid patterns on binding sites in protein complexes

    PubMed Central

    Kuo, Huang-Cheng; Ong, Ping-Lin; Lin, Jung-Chang; Huang, Jen-Peng

    2011-01-01

    Discovering amino acid (AA) patterns on protein binding sites has recently become popular. We propose a method to discover the association relationship among AAs on binding sites. Such knowledge of binding sites is very helpful in predicting protein-protein interactions. In this paper, we focus on protein complexes which have protein-protein recognition. The association rule mining technique is used to discover geographically adjacent amino acids on a binding site of a protein complex. When mining, instead of treating all AAs of binding sites as a transaction, we geographically partition AAs of binding sites in a protein complex. AAs in a partition are treated as a transaction. For the partition process, AAs on a binding site are projected from three-dimensional to two-dimensional. And then, assisted with a circular grid, AAs on the binding site are placed into grid cells. A circular grid has ten rings: a central ring, the second ring with 6 sectors, the third ring with 12 sectors, and later rings are added to four sectors in order. As for the radius of each ring, we examined the complexes and found that 10Å is a suitable range, which can be set by the user. After placing these recognition complexes on the circular grid, we obtain mining records (i.e. transactions) from each sector. A sector is regarded as a record. Finally, we use the association rule to mine these records for frequent AA patterns. If the support of an AA pattern is larger than the predetermined minimum support (i.e. threshold), it is called a frequent pattern. With these discovered patterns, we offer the biologists a novel point of view, which will improve the prediction accuracy of protein-protein recognition. In our experiments, we produced the AA patterns by data mining. As a result, we found that arginine (arg) most frequently appears on the binding sites of two proteins in the recognition protein complexes, while cysteine (cys) appears the fewest. In addition, if we discriminate the shape

  14. Discovering Alaska's Salmon: A Children's Activity Book.

    ERIC Educational Resources Information Center

    Devaney, Laurel

    This children's activity book helps students discover Alaska's salmon. Information is provided about salmon and where they live. The salmon life cycle and food chains are also discussed. Different kinds of salmon such as Chum Salmon, Chinook Salmon, Coho Salmon, Sockeye Salmon, and Pink Salmon are introduced, and various activities on salmon are…

  15. Rare Disorders and Diseases

    ERIC Educational Resources Information Center

    Umlauf, Mary; Monaco, Jana; FitzZaland, Mary; FitzZaland, Richard; Novitsky, Scott

    2008-01-01

    According to the National Organization for Rare Disorders (NORD), a rare or "orphan" disease affects fewer than 200,000 people in the United States. There are more than 6,000 rare disorders that, taken together, affect approximately 25 million Americans. "Exceptional Parent" ("EP") recognizes that when a disorder affects a child or adult, it…

  16. Discovering System Health Anomalies Using Data Mining Techniques

    NASA Technical Reports Server (NTRS)

    Sriastava, Ashok, N.

    2005-01-01

    We present a data mining framework for the analysis and discovery of anomalies in high-dimensional time series of sensor measurements that would be found in an Integrated System Health Monitoring system. We specifically treat the problem of discovering anomalous features in the time series that may be indicative of a system anomaly, or in the case of a manned system, an anomaly due to the human. Identification of these anomalies is crucial to building stable, reusable, and cost-efficient systems. The framework consists of an analysis platform and new algorithms that can scale to thousands of sensor streams to discovers temporal anomalies. We discuss the mathematical framework that underlies the system and also describe in detail how this framework is general enough to encompass both discrete and continuous sensor measurements. We also describe a new set of data mining algorithms based on kernel methods and hidden Markov models that allow for the rapid assimilation, analysis, and discovery of system anomalies. We then describe the performance of the system on a real-world problem in the aircraft domain where we analyze the cockpit data from aircraft as well as data from the aircraft propulsion, control, and guidance systems. These data are discrete and continuous sensor measurements and are dealt with seamlessly in order to discover anomalous flights. We conclude with recommendations that describe the tradeoffs in building an integrated scalable platform for robust anomaly detection in ISHM applications.

  17. Discovering and visualizing indirect associations between biomedical concepts

    PubMed Central

    Tsuruoka, Yoshimasa; Miwa, Makoto; Hamamoto, Kaisei; Tsujii, Jun'ichi; Ananiadou, Sophia

    2011-01-01

    Motivation: Discovering useful associations between biomedical concepts has been one of the main goals in biomedical text-mining, and understanding their biomedical contexts is crucial in the discovery process. Hence, we need a text-mining system that helps users explore various types of (possibly hidden) associations in an easy and comprehensible manner. Results: This article describes FACTA+, a real-time text-mining system for finding and visualizing indirect associations between biomedical concepts from MEDLINE abstracts. The system can be used as a text search engine like PubMed with additional features to help users discover and visualize indirect associations between important biomedical concepts such as genes, diseases and chemical compounds. FACTA+ inherits all functionality from its predecessor, FACTA, and extends it by incorporating three new features: (i) detecting biomolecular events in text using a machine learning model, (ii) discovering hidden associations using co-occurrence statistics between concepts, and (iii) visualizing associations to improve the interpretability of the output. To the best of our knowledge, FACTA+ is the first real-time web application that offers the functionality of finding concepts involving biomolecular events and visualizing indirect associations of concepts with both their categories and importance. Availability: FACTA+ is available as a web application at http://refine1-nactem.mc.man.ac.uk/facta/, and its visualizer is available at http://refine1-nactem.mc.man.ac.uk/facta-visualizer/. Contact: tsuruoka@jaist.ac.jp PMID:21685059

  18. Who discovered the sylvian fissure?

    PubMed

    Collice, Massimo; Collice, Rosa; Riva, Alessandro

    2008-10-01

    Cerebral convolutions were unknown until the 17th century. A constant sulcus was not recognized until the mid-1600s; it was named "the fissure of Sylvius," after the person who had always been considered as the one who discovered it. It is commonly asserted that the first description of the lateral scissure was made by Caspar Bartholin, who attributed its discovery to Sylvius. However, this was not actually the case, as Caspar Bartholin died in 1629, whereas Sylvius started studying medicine in 1632. The description could have been made either by Caspar Bartholin's son Thomas or by Sylvius himself. Irrespective of the description's author, the key to the history of the lateral fissure is that it was first identified by Fabrici d'Acquapendente in 1600, 40 years before Sylvius' description. In one of the 300 colored plates (Tabulae Pictae) by Fabrici, the lateral fissure is perfectly depicted, as are the temporal convolutions. Therefore, even if it was an accidental discovery, Fabrici should be the one noted as having discovered the fissure. This article ends with a short history of the plates. They were painted in oil on paper and were thought to further a great work, the Theatrum Totius Animalis Fabricae, which was begun in 1591 and never completed or published. Only the colored illustrations of this project remain. These plates were forgotten for more than 200 years, until they were rediscovered by Giuseppe Sterzi in 1909. They are among the best examples of anatomic iconography in terms of innovation, accuracy, and artistic accomplishment.

  19. Updating strategies for isolating and discovering giant viruses.

    PubMed

    Khalil, Jacques Yaacoub Bou; Andreani, Julien; La Scola, Bernard

    2016-06-01

    Almost fifteen years ago, the discovery of Acanthamoeba polyphaga mimivirus, the first giant virus, changed how we define a virus. It was discovered incidentally in a process of isolating Legionella sp. from environmental samples in the context of pneumonia epidemics using a co-culture system with Acanthamoeba. Since then, much effort and improvement has been put into the original technique. In addition to the known families of Mimiviridae and Marseilleviridae, four new proposed families of giant viruses have been isolated: Pandoravirus, Pithovirus, Faustovirus and Mollivirus. Major improvements were based on enrichment systems, targeted use of antibiotics and high-throughput methods. The most recent development, using flow cytometry for isolation and presumptive identification systems, opens a path to large environmental surveys that may discover new giant virus families in new protozoa supports used for culture support. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Boron Discovered in Ancient Habitable Mars Groundwater

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

    Gasda, Patrick

    Boron was recently discovered in calcium-sulfate veins on Mars using the ChemCam instrument on NASA’s Curiosity Mars Rover. This is the first Mars mission to detect boron on the Red Planet. Los Alamos Post-Doctoral Student Patrick Gasda explains how this discovery helps us better understand the timescale of habitability on Mars.

  1. Discover Presidential Log Cabins. Teacher's Discussion Guide.

    ERIC Educational Resources Information Center

    National Park Service (Dept. of Interior), Washington, DC.

    Discover Presidential Log Cabins is a set of materials designed to help educate 6-8 grade students about the significance of three log cabin sites occupied by George Washington, Ulysses Grant, Abraham Lincoln, and Theodore Roosevelt. This teacher's discussion guide is intended for use as part of a larger, comprehensive social studies program, and…

  2. DISCOVER AQ Research Plane Arrives

    NASA Image and Video Library

    2011-06-28

    A 117-foot P-3B NASA research aircraft is seen on the tarmac at Baltimore/Washington International Thurgood Marshall Airport, Tuesday, June 28, 2011, in Baltimore, Md. The aircraft is part of a month-long field campaign designed to improve satellite measurements of air pollution. The name of the experiment -- Deriving Information on Surface conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER -- AQ) -- is a mouthful, but its purpose is simple. Come July, the aircraft will be flying spirals over six ground stations in Maryland. Photo Credit: (NASA/Paul E. Alers)

  3. DISCOVER AQ Research Plane Arrives

    NASA Image and Video Library

    2011-06-28

    Pilots Shane Dover, left, and Mike Singer are seen on the flight deck of the P-3B NASA research aircraft at Baltimore/Washington International Thurgood Marshall Airport, Tuesday, June 28, 2011, in Baltimore, Md. The aircraft is part of a month-long field campaign designed to improve satellite measurements of air pollution. The name of the experiment -- Deriving Information on Surface conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER -- AQ) -- is a mouthful, but its purpose is simple. Come July, the aircraft will be flying spirals over six ground stations in Maryland. Photo Credit: (NASA/Paul E. Alers)

  4. The pearls of using real-world evidence to discover social groups

    NASA Astrophysics Data System (ADS)

    Cardillo, Raymond A.; Salerno, John J.

    2005-03-01

    In previous work, we introduced a new paradigm called Uni-Party Data Community Generation (UDCG) and a new methodology to discover social groups (a.k.a., community models) called Link Discovery based on Correlation Analysis (LDCA). We further advanced this work by experimenting with a corpus of evidence obtained from a Ponzi scheme investigation. That work identified several UDCG algorithms, developed what we called "Importance Measures" to compare the accuracy of the algorithms based on ground truth, and presented a Concept of Operations (CONOPS) that criminal investigators could use to discover social groups. However, that work used a rather small random sample of manually edited documents because the evidence contained far too many OCR and other extraction errors. Deferring the evidence extraction errors allowed us to continue experimenting with UDCG algorithms, but only used a small fraction of the available evidence. In attempt to discover techniques that are more practical in the near-term, our most recent work focuses on being able to use an entire corpus of real-world evidence to discover social groups. This paper discusses the complications of extracting evidence, suggests a method of performing name resolution, presents a new UDCG algorithm, and discusses our future direction in this area.

  5. Discovering frequently recurring movement sequences in team-sport athlete spatiotemporal data.

    PubMed

    Sweeting, Alice J; Aughey, Robert J; Cormack, Stuart J; Morgan, Stuart

    2017-12-01

    Athlete external load is typically analysed from predetermined movement thresholds. The combination of movement sequences and differences in these movements between playing positions is also currently unknown. This study developed a method to discover the frequently recurring movement sequences across playing position during matches. The external load of 12 international female netball athletes was collected by a local positioning system during four national-level matches. Velocity, acceleration and angular velocity were calculated from positional (X, Y) data, clustered via one-dimensional k-means and assigned a unique alphabetic label. Combinations of velocity, acceleration and angular velocity movement were compared using the Levenshtein distance and similarities computed by the longest common substring problem. The contribution of each movement sequence, according to playing position and relative to the wider data set, was then calculated via the Minkowski distance. A total of 10 frequently recurring combinations of movement were discovered, regardless of playing position. Only the wing attack, goal attack and goal defence playing positions are closely related. We developed a technique to discover the movement sequences, according to playing position, performed by elite netballers. This methodology can be extended to discover the frequently recurring movements within other team sports and across levels of competition.

  6. A strategy to discover new organizers identifies a putative heart organizer

    PubMed Central

    Anderson, Claire; Khan, Mohsin A. F.; Wong, Frances; Solovieva, Tatiana; Oliveira, Nidia M. M.; Baldock, Richard A.; Tickle, Cheryll; Burt, Dave W.; Stern, Claudio D.

    2016-01-01

    Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development. PMID:27557800

  7. Functional impact of global rare copy number variation in autism spectrum disorders.

    PubMed

    Pinto, Dalila; Pagnamenta, Alistair T; Klei, Lambertus; Anney, Richard; Merico, Daniele; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R; Correia, Catarina; Abrahams, Brett S; Almeida, Joana; Bacchelli, Elena; Bader, Gary D; Bailey, Anthony J; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Bryson, Susan E; Carson, Andrew R; Casallo, Guillermo; Casey, Jillian; Chung, Brian H Y; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L; Crossett, Andrew; Cytrynbaum, Cheryl; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A; Folstein, Susan E; Fombonne, Eric; Freitag, Christine M; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T; Goldberg, Jeremy; Green, Andrew; Green, Jonathan; Guter, Stephen J; Hakonarson, Hakon; Heron, Elizabeth A; Hill, Matthew; Holt, Richard; Howe, Jennifer L; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M; Lamb, Janine A; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L; Lionel, Anath C; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R; McConachie, Helen; McDougle, Christopher J; McGrath, Jane; McMahon, William M; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J; Mirza, Ghazala K; Munson, Jeff; Nelson, Stanley F; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Pilorge, Marion; Piven, Joseph; Ponting, Chris P; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L; Bierut, Laura J; Rice, John P; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Sequeira, Ana F; Senman, Lili; Shah, Naisha; Sheffield, Val C; Soorya, Latha; Sousa, Inês; Stein, Olaf; Sykes, Nuala; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H; Webber, Caleb; Weksberg, Rosanna; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Wu, Jing; Yaspan, Brian L; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Buxbaum, Joseph D; Cantor, Rita M; Cook, Edwin H; Coon, Hilary; Cuccaro, Michael L; Devlin, Bernie; Ennis, Sean; Gallagher, Louise; Geschwind, Daniel H; Gill, Michael; Haines, Jonathan L; Hallmayer, Joachim; Miller, Judith; Monaco, Anthony P; Nurnberger, John I; Paterson, Andrew D; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Szatmari, Peter; Vicente, Astrid M; Vieland, Veronica J; Wijsman, Ellen M; Scherer, Stephen W; Sutcliffe, James S; Betancur, Catalina

    2010-07-15

    The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.

  8. Alkaptonuria: An example of a "fundamental disease"--A rare disease with important lessons for more common disorders.

    PubMed

    Gallagher, James A; Dillon, Jane P; Sireau, Nicolas; Timmis, Oliver; Ranganath, Lakshminarayan R

    2016-04-01

    "Fundamental diseases" is a term introduced by the charity Findacure to describe rare genetic disorders that are gateways to understanding common conditions and human physiology. The concept that rare diseases have important lessons for biomedical science has been recognised by some of the great figures in the history of medical research, including Harvey, Bateson and Garrod. Here we describe some of the recently discovered lessons from the study of the iconic genetic disease alkaptonuria (AKU), which have shed new light on understanding the pathogenesis of osteoarthritis. In AKU, ochronotic pigment is deposited in cartilage when collagen fibrils become susceptible to attack by homogentisic acid (HGA). When HGA binds to collagen, cartilage matrix becomes stiffened, resulting in the aberrant transmission of loading to underlying subchondral bone. Aberrant loading leads to the formation of pathophysiological structures including trabecular excrescences and high density mineralised protrusions (HDMPs). These structures initially identified in AKU have subsequently been found in more common osteoarthritis and appear to play a role in joint destruction in both diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. The burden of rare cancers in Italy: the surveillance of rare cancers in Italy (RITA) project.

    PubMed

    Trama, Annalisa; Mallone, Sandra; Ferretti, Stefano; Meduri, Francesca; Capocaccia, Riccardo; Gatta, Gemma

    2012-01-01

    The project Surveillance of rare cancers in Italy (RITA) provides, for the first time, estimates of the burden of rare cancers in Italy based on the list of rare cancers proposed in collaboration with the European project Surveillance of Rare Cancers in Europe (RARECARE). RITA analyzed data from Italian population-based cancer registries (CR). The period of diagnosis was 1988 to 2002, and vital status information was available up to December 31, 2003. Incidence rates were estimated for the period 1995-2002, survival for the years 2000-2002 (with the period method of Brenner), and complete prevalence at January 1, 2003. Rare cancers are those with an incidence <6/100,000/year. In Italy, every year there are 60,000 new diagnoses of rare cancers corresponding to 15% of all new cancer diagnoses. Five-year relative survival was on the average worse for rare cancers (53%) than for common cancers (73%). A total of 770,000 patients were living in Italy in 2008 with a diagnosis of a rare cancer, 22% of the total cancer prevalence. Our estimates constitute a useful base for further research and support the idea that rare cancers are a public health problem that deserves attention. Centers of expertise for rare cancers that pool cases, expertise and resources could ensure an adequate clinical management for these diseases. Our data also showed that cancer registries are suitable sources of data to estimate incidence, prevalence and survival for rare cancers and should continue to monitoring rare cancers in Italy.

  10. Recycling of rare earth metals from rare earth-transition metal alloy scrap by liquid metal extraction

    DOEpatents

    Ellis, Timothy W.; Schmidt, Frederick A.

    1995-08-01

    Method of treating rare earth metal-bearing scrap, waste or other material (e.g. Nd--Fe--B or Dy--Tb--Fe scrap) to recover the rare earth metal comprising melting the rare earth metal-bearing material, melting a Group IIA metal extractant, such as Mg, Ca, or Ba, in which the rare earth is soluble in the molten state, and contacting the melted material and melted extractant at a temperature and for a time effective to extract the rare earth from the melted material into the melted extractant. The rare earth metal is separated from the extractant metal by vacuum sublimation or distillation.

  11. Dive and Discover : Expeditions to the Seafloor

    Science.gov Websites

    me a link other What is your highest level of education? -- please select -- K-12 student High School : Are you a teacher? Yes No Email: Your email will not be revealed to any third party, nor be used for Us | Contact © 2005 Dive and Discover is a registered trademark of Woods Hole Oceanographic

  12. DISCOVER AQ Research Plane Arrives

    NASA Image and Video Library

    2011-06-28

    WFF Pilots Mike Singer, left, and Shane Dover stand in front of the 117-foot P-3B NASA research aircraft on the tarmac at Baltimore/Washington International Thurgood Marshall Airport, Tuesday, June 28, 2011, in Baltimore, Md. The aircraft is part of a month-long field campaign designed to improve satellite measurements of air pollution. The name of the experiment -- Deriving Information on Surface conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER -- AQ) -- is a mouthful, but its purpose is simple. Come July, the aircraft will be flying spirals over six ground stations in Maryland. Photo Credit: (NASA/Paul E. Alers)

  13. Communicating Finnish Quietude: A Pedagogical Process for Discovering Implicit Cultural Meanings in Languages

    ERIC Educational Resources Information Center

    Berry, Michael; Carbaugh, Donal; Nurmikari-Berry, Marjatta

    2004-01-01

    This paper introduces a pedagogical approach to integrating intercultural communication into language learning. The focus is on the development of competence in discovering and interpreting cultural meanings when communicating in English as an international language. The analyses of data which students produced illustrates how discovering implicit…

  14. Recycling of rare earth metals from rare earth-transition metal alloy scrap by liquid metal extraction

    DOEpatents

    Ellis, T.W.; Schmidt, F.A.

    1995-08-01

    A method is described for treating rare earth metal-bearing scrap, waste or other material (e.g. Nd--Fe--B or Dy--Tb--Fe scrap) to recover the rare earth metal comprising melting the rare earth metal-bearing material, melting a Group IIA metal extractant, such as Mg, Ca, or Ba, in which the rare earth is soluble in the molten state, and contacting the melted material and melted extractant at a temperature and for a time effective to extract the rare earth from the melted material into the melted extractant. The rare earth metal is separated from the extractant metal by vacuum sublimation or distillation. 2 figs.

  15. Discover Earth: Earth's Energy Budget or Can You Spare a Sun?

    NASA Technical Reports Server (NTRS)

    Gates, Tom; Peters, Dale E.; Steeley, Jeanne

    1999-01-01

    Discover Earth is a NASA-sponsored project for teachers of grades 5-12, designed to: enhance understanding of the Earth as an integrated system enhance the interdisciplinary approach to science instruction, and provide classroom materials that focus on those goals. Discover Earth is conducted by the Institute for Global Environmental Strategies in collaboration with Dr. Eric Barron, Director, Earth System Science Center, The Pennsylvania State University; and Dr. Robert Hudson, Chair, the Department of Meteorology, University of Maryland at College Park.

  16. A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

    PubMed

    Bell, Stuart A; Tudur Smith, Catrin

    2014-11-26

    To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

  17. Discovering loose group movement patterns from animal trajectories

    USGS Publications Warehouse

    Wang, Yuwei; Luo, Ze; Xiong, Yan; Prosser, Diann J.; Newman, Scott H.; Takekawa, John Y.; Yan, Baoping

    2015-01-01

    The technical advances of positioning technologies enable us to track animal movements at finer spatial and temporal scales, and further help to discover a variety of complex interactive relationships. In this paper, considering the loose gathering characteristics of the real-life groups' members during the movements, we propose two kinds of loose group movement patterns and corresponding discovery algorithms. Firstly, we propose the weakly consistent group movement pattern which allows the gathering of a part of the members and individual temporary leave from the whole during the movements. To tolerate the high dispersion of the group at some moments (i.e. to adapt the discontinuity of the group's gatherings), we further scheme the weakly consistent and continuous group movement pattern. The extensive experimental analysis and comparison with the real and synthetic data shows that the group pattern discovery algorithms proposed in this paper are similar to the the real-life frequent divergences of the members during the movements, can discover more complete memberships, and have considerable performance.

  18. A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans

    PubMed Central

    Timpson, Nicholas J.; Walter, Klaudia; Min, Josine L.; Tachmazidou, Ioanna; Malerba, Giovanni; Shin, So-Youn; Chen, Lu; Futema, Marta; Southam, Lorraine; Iotchkova, Valentina; Cocca, Massimiliano; Huang, Jie; Memari, Yasin; McCarthy, Shane; Danecek, Petr; Muddyman, Dawn; Mangino, Massimo; Menni, Cristina; Perry, John R. B.; Ring, Susan M.; Gaye, Amadou; Dedoussis, George; Farmaki, Aliki-Eleni; Burton, Paul; Talmud, Philippa J.; Gambaro, Giovanni; Spector, Tim D.; Smith, George Davey; Durbin, Richard; Richards, J Brent; Humphries, Steve E.; Zeggini, Eleftheria; Soranzo, Nicole; Al Turki, Saeed; Anderson, Carl; Anney, Richard; Antony, Dinu; Soler Artigas, Maria; Ayub, Muhammad; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Barroso, Inês; Beales, Phil; Bentham, Jamie; Bhattacharya, Shoumo; Birney, Ewan; Blackwood, Douglas; Bobrow, Martin; Bochukova, Elena; Bolton, Patrick; Bounds, Rebecca; Boustred, Chris; Breen, Gerome; Calissano, Mattia; Carss, Keren; Chatterjee, Krishna; Chen, Lu; Ciampi, Antonio; Cirak, Sebhattin; Clapham, Peter; Clement, Gail; Coates, Guy; Collier, David; Cosgrove, Catherine; Cox, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Curtis, David; Daly, Allan; Danecek, Petr; Davey Smith, George; Day-Williams, Aaron; Day, Ian N. M.; Down, Thomas; Du, Yuanping; Dunham, Ian; Durbin, Richard; Edkins, Sarah; Ellis, Peter; Evans, David; Faroogi, Sadaf; Fatemifar, Ghazaleh; Fitzpatrick, David R.; Flicek, Paul; Flyod, James; Foley, A Reghan; Franklin, Christopher S; Futema, Marta; Gallagher, Louise; Gaunt, Tom; Geihs, Matthias; Geschwind, Daniel; Greenwood, Celia; Griffin, Heather; Grozeva, Detelina; Guo, Xueqin; Guo, Xiaosen; Gurling, Hugh; Hart, Deborah; Hendricks, Audrey; Holmans, Peter; Howie, Bryan; Huang, Jie; Huang, Liren; Hubbard, Tim; Humphries, Steve E.; Hurles, Matthew E.; Hysi, Pirro; Jackson, David K.; Jamshidi, Yalda; Jing, Tian; Joyce, Chris; Kaye, Jane; Keane, Thomas; Keogh, Julia; Kemp, John; Kennedy, Karen; Kolb-Kokocinski, Anja; Lachance, Genevieve; Langford, Cordelia; Lawson, Daniel; Lee, Irene; Lek, Monkol; Liang, Jieqin; Lin, Hong; Li, Rui; Li, Yingrui; Liu, Ryan; Lönnqvist, Jouko; Lopes, Margarida; Lotchkova, Valentina; MacArthur, Daniel; Marchini, Jonathan; Maslen, John; Massimo, Mangino; Mathieson, Iain; Marenne, Gaëlle; McCarthy, Shane; McGuffin, Peter; McIntosh, Andrew; McKechanie, Andrew G.; McQuillin, Andrew; Memari, Yasin; Metrustry, Sarah; Min, Josine; Mitchison, Hannah; Moayyeri, Alireza; Morris, James; Muddyman, Dawn; Muntoni, Francesco; Northstone, Kate; O'Donnovan, Michael; Onoufriadis, Alexandros; O'Rahilly, Stephen; Oualkacha, Karim; Owen, Michael J.; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy R.; Paternoster, Lavinia; Paunio, Tiina; Payne, Felicity; Perry, John; Pietilainen, Olli; Plagnol, Vincent; Quaye, Lydia; Quail, Michael A.; Raymond, Lucy; Rehnström, Karola; Richards, Brent; Ring, Susan; Ritchie, Graham R. S.; Roberts, Nicola; Savage, David B.; Scambler, Peter; Schiffels, Stephen; Schmidts, Miriam; Schoenmakers, Nadia; Semple, Robert K.; Serra, Eva; Sharp, Sally I.; Shihab, Hasheem; Shin, So-Youn; Skuse, David; Small, Kerrin; Soranzo, Nicole; Southam, Lorraine; Spasic-Boskovic, Olivera; Spector, Tim; St Clair, David; Stalker, Jim; Stevens, Elizabeth; St Pourcian, Beate; Sun, Jianping; Surdulescu, Gabriela; Suvisaari, Jaana; Tachmazidou, Ionna; Timpson, Nicholas; Tobin, Martin D.; Valdes, Ana; Van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Visscher, Peter M.; Wain, Louise V.; Walter, Klaudia; Walters, James T. R.; Wang, Guangbiao; Wang, Jun; Wang, Yu; Ward, Kirsten; Wheeler, Elanor; Whyte, Tamieka; Williams, Hywel; Williamson, Kathleen A.; Wilson, Crispian; Wilson, Scott G.; Wong, Kim; Xu, ChangJiang; Yang, Jian; Zeggini, Eleftheria; Zhang, Fend; Zhang, Pingbo; Zheng, Hou-Feng

    2014-01-01

    The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (−1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10−8)) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (−1.0 s.d. (s.e.=0.173), P-value=7.32 × 10−9). This is consistent with an effect between 0.5 and 1.5 mmol l−1 dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale. PMID:25225788

  19. Fast Ss-Ilm a Computationally Efficient Algorithm to Discover Socially Important Locations

    NASA Astrophysics Data System (ADS)

    Dokuz, A. S.; Celik, M.

    2017-11-01

    Socially important locations are places which are frequently visited by social media users in their social media lifetime. Discovering socially important locations provide several valuable information about user behaviours on social media networking sites. However, discovering socially important locations are challenging due to data volume and dimensions, spatial and temporal calculations, location sparseness in social media datasets, and inefficiency of current algorithms. In the literature, several studies are conducted to discover important locations, however, the proposed approaches do not work in computationally efficient manner. In this study, we propose Fast SS-ILM algorithm by modifying the algorithm of SS-ILM to mine socially important locations efficiently. Experimental results show that proposed Fast SS-ILM algorithm decreases execution time of socially important locations discovery process up to 20 %.

  20. Refined potentials for rare gas atom adsorption on rare gas and alkali-halide surfaces

    NASA Technical Reports Server (NTRS)

    Wilson, J. W.; Heinbockel, J. H.; Outlaw, R. A.

    1985-01-01

    The utilization of models of interatomic potential for physical interaction to estimate the long range attractive potential for rare gases and ions is discussed. The long range attractive force is calculated in terms of the atomic dispersion properties. A data base of atomic dispersion parameters for rare gas atoms, alkali ion, and halogen ions is applied to the study of the repulsive core; the procedure for evaluating the repulsive core of ion interactions is described. The interaction of rare gas atoms on ideal rare gas solid and alkali-halide surfaces is analyzed; zero coverage absorption potentials are derived.

  1. Integrating common and rare genetic variation in diverse human populations.

    PubMed

    Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Dermitzakis, Emmanouil; Schaffner, Stephen F; Yu, Fuli; Peltonen, Leena; Dermitzakis, Emmanouil; Bonnen, Penelope E; Altshuler, David M; Gibbs, Richard A; de Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Palotie, Aarno; Parkin, Melissa; Whittaker, Pamela; Yu, Fuli; Chang, Kyle; Hawes, Alicia; Lewis, Lora R; Ren, Yanru; Wheeler, David; Gibbs, Richard A; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M; Kristiansson, Kati; Lee, Charles; McCarrol, Steven A; Nemesh, James; Dermitzakis, Emmanouil; Keinan, Alon; Montgomery, Stephen B; Pollack, Samuela; Price, Alkes L; Soranzo, Nicole; Bonnen, Penelope E; Gibbs, Richard A; Gonzaga-Jauregui, Claudia; Keinan, Alon; Price, Alkes L; Yu, Fuli; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Schaffner, Stephen F; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Price, Alkes L; Schaffner, Stephen F; Takeuchi, Fumihiko; Grossman, Sharon R; Shlyakhter, Ilya; Hostetter, Elizabeth B; Sabeti, Pardis C; Adebamowo, Clement A; Foster, Morris W; Gordon, Deborah R; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N; Royal, Charmaine D; Sharp, Richard R; Zeng, Changqing; Brooks, Lisa D; McEwen, Jean E

    2010-09-02

    Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of discovered CNPs and SNPs. This expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.

  2. RApid Temporal Survey (RATS) - II. Followup observations of four newly discovered short-period variables

    NASA Astrophysics Data System (ADS)

    Ramsay, Gavin; Napiwotzki, Ralf; Hakala, Pasi; Lehto, Harry

    2006-09-01

    The Rapid Temporal Survey (RATS) is a survey to detect objects whose optical intensity varies on time-scales of less than ~70 min. In our pilot data set taken with the Isaac Newton Telescope and the Wide Field Camera in 2003 November, we discovered nearly 50 new variable objects. Many of these varied on time-scales much longer than 1 h. However, only four objects showed a modulation on a time-scale of 1 h or less. This paper presents followup optical photometry and spectroscopy of these four objects. We find that RATJ0455 + 1305 is a pulsating (on a period of 374 s) subdwarf B star of the EC14026 type. We have modelled its spectrum and determine Teff = 29200 +/- 1900K and logg = 5.2 +/- 0.3 which locates it on the cool edge of the EC14026 instability strip. It has a modulation amplitude which is one of the highest of any known EC14026 star. Based on their spectra, photometric variability and their infrared colours, we find that RATJ0449 + 1756, J0455 + 1254 and J0807 + 1510 are likely to be SX Phe stars - dwarf δ Sct stars. Our results show that our observing strategy is a good method for finding rare pulsating stars.

  3. ISM Properties of a Massive Dusty Star-forming Galaxy Discovered at z ˜ 7

    NASA Astrophysics Data System (ADS)

    Strandet, M. L.; Weiss, A.; De Breuck, C.; Marrone, D. P.; Vieira, J. D.; Aravena, M.; Ashby, M. L. N.; Béthermin, M.; Bothwell, M. S.; Bradford, C. M.; Carlstrom, J. E.; Chapman, S. C.; Cunningham, D. J. M.; Chen, Chian-Chou; Fassnacht, C. D.; Gonzalez, A. H.; Greve, T. R.; Gullberg, B.; Hayward, C. C.; Hezaveh, Y.; Litke, K.; Ma, J.; Malkan, M.; Menten, K. M.; Miller, T.; Murphy, E. J.; Narayanan, D.; Phadke, K. A.; Rotermund, K. M.; Spilker, J. S.; Sreevani, J.

    2017-06-01

    We report the discovery and constrain the physical conditions of the interstellar medium of the highest-redshift millimeter-selected dusty star-forming galaxy to date, SPT-S J031132-5823.4 (hereafter SPT0311-58), at z=6.900+/- 0.002. SPT0311-58 was discovered via its 1.4 mm thermal dust continuum emission in the South Pole Telescope (SPT)-SZ survey. The spectroscopic redshift was determined through an Atacama Large Millimeter/submillimeter Array 3 mm frequency scan that detected CO(6-5), CO(7-6), and [{{C}} {{I}}](2-1), and subsequently was confirmed by detections of CO(3-2) with the Australia Telescope Compact Array and [{{C}} {{II}}] with APEX. We constrain the properties of the ISM in SPT0311-58 with a radiative transfer analysis of the dust continuum photometry and the CO and [{{C}} {{I}}] line emission. This allows us to determine the gas content without ad hoc assumptions about gas mass scaling factors. SPT0311-58 is extremely massive, with an intrinsic gas mass of {M}{gas}=3.3+/- 1.9× {10}11 {M}⊙ . Its large mass and intense star formation is very rare for a source well into the epoch of reionization.

  4. Discovering Hidden Analogies in an Online Humanities Database.

    ERIC Educational Resources Information Center

    Cory, Kenneth A.

    1999-01-01

    Drawing upon an efficacious method for discovering previously unknown causes of medical syndromes and searching in the Humanities Index, an illuminating new humanities analogy between the epistemological ideas of Robert Frost and the ancient Greek philosopher Carneades was found by constructing a search statement in which proper names were coupled…

  5. Dyspareunia in a Teenager Reveals a Rare Occurrence: Retroperitoneal Cervical Leiomyoma of the Left Pararectal Space.

    PubMed

    Giannella, Luca; Mfuta, Kabala; Tuzio, Antonella; Cerami, Lillo Bruno

    2016-02-01

    Retroperitoneal uterine leiomyoma is a very rare occurrence and to discover it as a cause of female sexual dysfunction in a teen is unusual. An 18-year-old black woman reported deep dyspareunia, resulting in severe distress. Gynecological and instrumental examinations showed a pelvic mass of 7 cm in diameter. The preoperative diagnosis was uterine fibroid, but the exact location of the leiomyoma was uncertain. Laparoscopic examination showed a pedunculated retroperitoneal cervical leiomyoma in the left pararectal space. After surgical excision of the mass, normal sexual activity was restored. When a teen experiences pain with intercourse, pelvic masses should be part of differential diagnosis of dyspareunia. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  6. Ames Lab 101: Rare Earths

    ScienceCinema

    Gschneidner, Karl

    2017-12-11

    "Mr. Rare Earth," Ames Laboratory scientist Karl Gschneidner Jr., explains the importance of rare-earth materials in many of the technologies we use today -- ranging from computers to hybrid cars to wind turbines. Gschneidner is a world renowned rare-earths expert at the U.S. Department of Energy's Ames Laboratory.

  7. Plant Biofilm Inhibitors to Discover Biofilm Genes

    DTIC Science & Technology

    2011-04-08

    REPORT Final Report for Plant Biofilm Inhibitors to Discover Biofilm Genes 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: To control biofilms , we have...synthesized the natural biofilm inhibitor (5Z)-4-bromo-5-(bromomethylene) -3-butyl-2(5H)-furanone from the red alga Delisea pulchra and determined that...Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 15. SUBJECT TERMS biofilms , biofilm inhibitors Thomas K. Wood Texas Engineering

  8. Not so Rare, Rare Diseases

    ERIC Educational Resources Information Center

    Waldman, H. Barry; Perlman, Steven P.; Munter, Beverly L.; Chaudhry, Ramiz A.

    2008-01-01

    A rare disease or condition is defined by federal legislation such that it: (1) affects less than 200,000 persons in the U.S.; or (2) affects more than 200,000 persons in the U.S. but for which there is no reasonable expectation that the cost of developing and making available in the U.S. a drug for such disease or condition will be recovered from…

  9. Discovering graphical Granger causality using the truncating lasso penalty

    PubMed Central

    Shojaie, Ali; Michailidis, George

    2010-01-01

    Motivation: Components of biological systems interact with each other in order to carry out vital cell functions. Such information can be used to improve estimation and inference, and to obtain better insights into the underlying cellular mechanisms. Discovering regulatory interactions among genes is therefore an important problem in systems biology. Whole-genome expression data over time provides an opportunity to determine how the expression levels of genes are affected by changes in transcription levels of other genes, and can therefore be used to discover regulatory interactions among genes. Results: In this article, we propose a novel penalization method, called truncating lasso, for estimation of causal relationships from time-course gene expression data. The proposed penalty can correctly determine the order of the underlying time series, and improves the performance of the lasso-type estimators. Moreover, the resulting estimate provides information on the time lag between activation of transcription factors and their effects on regulated genes. We provide an efficient algorithm for estimation of model parameters, and show that the proposed method can consistently discover causal relationships in the large p, small n setting. The performance of the proposed model is evaluated favorably in simulated, as well as real, data examples. Availability: The proposed truncating lasso method is implemented in the R-package ‘grangerTlasso’ and is freely available at http://www.stat.lsa.umich.edu/∼shojaie/ Contact: shojaie@umich.edu PMID:20823316

  10. Why some plant species are rare.

    PubMed

    Wieger Wamelink, G W; Wamelink, G W Weiger; Goedhart, Paul W; Frissel, Joep; Frissel, Josep Y

    2014-01-01

    Biodiversity, including plant species diversity, is threatened worldwide as a result of anthropogenic pressures such as an increase of pollutants and climate change. Rare species in particular are on the verge of becoming extinct. It is still unclear as to why some plant species are rare and others are not. Are they rare due to: intrinsic reasons, dispersal capacity, the effects of management or abiotic circumstances? Habitat preference of rare plant species may play an important role in determining why some species are rare. Based on an extensive data set of soil parameters we investigated if rarity is due to a narrow habitat preference for abiotic soil parameters. For 23 different abiotic soil parameters, of which the most influential were groundwater-table, soil-pH and nutrient-contents, we estimated species responses for common and rare species. Based on the responses per species we calculated the range of occurrence, the range between the 5 and 95 percentile of the response curve giving the habitat preference. Subsequently, we calculated the average response range for common and rare species. In addition, we designed a new graphic in order to provide a better means for presentation of the results. The habitat preferences of rare species for abiotic soil conditions are significantly narrower than for common species. Twenty of the twenty-three abiotic parameters showed on average significantly narrower habitat preferences for rare species than for common species; none of the abiotic parameters showed on average a narrower habitat preference for common species. The results have major implications for the conservation of rare plant species; accordingly management and nature development should be focussed on the maintenance and creation of a broad range of environmental conditions, so that the requirements of rare species are met. The conservation of (abiotic) gradients within ecosystems is particularly important for preserving rare species.

  11. Discovering disease-associated genes in weighted protein-protein interaction networks

    NASA Astrophysics Data System (ADS)

    Cui, Ying; Cai, Meng; Stanley, H. Eugene

    2018-04-01

    Although there have been many network-based attempts to discover disease-associated genes, most of them have not taken edge weight - which quantifies their relative strength - into consideration. We use connection weights in a protein-protein interaction (PPI) network to locate disease-related genes. We analyze the topological properties of both weighted and unweighted PPI networks and design an improved random forest classifier to distinguish disease genes from non-disease genes. We use a cross-validation test to confirm that weighted networks are better able to discover disease-associated genes than unweighted networks, which indicates that including link weight in the analysis of network properties provides a better model of complex genotype-phenotype associations.

  12. Raman scattering of rare earth hexaborides

    NASA Astrophysics Data System (ADS)

    Ogita, Norio; Hasegawa, Takumi; Udagawa, Masayuki; Iga, Fumitoshi; Kunii, Satoru

    2009-06-01

    Raman scattering spectra were measured for the rare-earth hexaborides RB6 (R = Ce, Gd, or Dy). All Raman-active phonons due to B6 vibrations were observed in the range 600 - 1400 cm-1. Anomalous peaks were detected below 200 cm-1, which correspond to vibrations of rare-earth ion excited by second-order Raman scattering process. The intensity and energy of the rare-earth mode decrease with decreasing temperature. This suggests that the rare-earth ion vibrates in a shallow and anharmonic potential due to the boron cage. Using the reported values of mean square displacement of rare-earth ion, we estimated the anharmonic contribution for the rare-earth vibrations.

  13. Symmetry compression method for discovering network motifs.

    PubMed

    Wang, Jianxin; Huang, Yuannan; Wu, Fang-Xiang; Pan, Yi

    2012-01-01

    Discovering network motifs could provide a significant insight into systems biology. Interestingly, many biological networks have been found to have a high degree of symmetry (automorphism), which is inherent in biological network topologies. The symmetry due to the large number of basic symmetric subgraphs (BSSs) causes a certain redundant calculation in discovering network motifs. Therefore, we compress all basic symmetric subgraphs before extracting compressed subgraphs and propose an efficient decompression algorithm to decompress all compressed subgraphs without loss of any information. In contrast to previous approaches, the novel Symmetry Compression method for Motif Detection, named as SCMD, eliminates most redundant calculations caused by widespread symmetry of biological networks. We use SCMD to improve three notable exact algorithms and two efficient sampling algorithms. Results of all exact algorithms with SCMD are the same as those of the original algorithms, since SCMD is a lossless method. The sampling results show that the use of SCMD almost does not affect the quality of sampling results. For highly symmetric networks, we find that SCMD used in both exact and sampling algorithms can help get a remarkable speedup. Furthermore, SCMD enables us to find larger motifs in biological networks with notable symmetry than previously possible.

  14. Discovering Sequence Motifs with Arbitrary Insertions and Deletions

    PubMed Central

    Frith, Martin C.; Saunders, Neil F. W.; Kobe, Bostjan; Bailey, Timothy L.

    2008-01-01

    Biology is encoded in molecular sequences: deciphering this encoding remains a grand scientific challenge. Functional regions of DNA, RNA, and protein sequences often exhibit characteristic but subtle motifs; thus, computational discovery of motifs in sequences is a fundamental and much-studied problem. However, most current algorithms do not allow for insertions or deletions (indels) within motifs, and the few that do have other limitations. We present a method, GLAM2 (Gapped Local Alignment of Motifs), for discovering motifs allowing indels in a fully general manner, and a companion method GLAM2SCAN for searching sequence databases using such motifs. glam2 is a generalization of the gapless Gibbs sampling algorithm. It re-discovers variable-width protein motifs from the PROSITE database significantly more accurately than the alternative methods PRATT and SAM-T2K. Furthermore, it usefully refines protein motifs from the ELM database: in some cases, the refined motifs make orders of magnitude fewer overpredictions than the original ELM regular expressions. GLAM2 performs respectably on the BAliBASE multiple alignment benchmark, and may be superior to leading multiple alignment methods for “motif-like” alignments with N- and C-terminal extensions. Finally, we demonstrate the use of GLAM2 to discover protein kinase substrate motifs and a gapped DNA motif for the LIM-only transcriptional regulatory complex: using GLAM2SCAN, we identify promising targets for the latter. GLAM2 is especially promising for short protein motifs, and it should improve our ability to identify the protein cleavage sites, interaction sites, post-translational modification attachment sites, etc., that underlie much of biology. It may be equally useful for arbitrarily gapped motifs in DNA and RNA, although fewer examples of such motifs are known at present. GLAM2 is public domain software, available for download at http://bioinformatics.org.au/glam2. PMID:18437229

  15. Discover Primary Science: Developing Primary Science in Ireland

    ERIC Educational Resources Information Center

    Horner, Margaret; Palmer, Marion

    2007-01-01

    "Discover Primary Science" is a major project in primary science education in Ireland. In 2006-2007 it involves 2400 primary schools, 45 host centres, and two government departments. However, it started out as a local initiative taken by one state agency in 2002 involving four Institutes of Technology and 40 primary schools. The aim of…

  16. A comprehensive global genotype-phenotype database for rare diseases.

    PubMed

    Trujillano, Daniel; Oprea, Gabriela-Elena; Schmitz, Yvonne; Bertoli-Avella, Aida M; Abou Jamra, Rami; Rolfs, Arndt

    2017-01-01

    The ability to discover genetic variants in a patient runs far ahead of the ability to interpret them. Databases with accurate descriptions of the causal relationship between the variants and the phenotype are valuable since these are critical tools in clinical genetic diagnostics. Here, we introduce a comprehensive and global genotype-phenotype database focusing on rare diseases. This database (CentoMD ® ) is a browser-based tool that enables access to a comprehensive, independently curated system utilizing stringent high-quality criteria and a quickly growing repository of genetic and human phenotype ontology (HPO)-based clinical information. Its main goals are to aid the evaluation of genetic variants, to enhance the validity of the genetic analytical workflow, to increase the quality of genetic diagnoses, and to improve evaluation of treatment options for patients with hereditary diseases. The database software correlates clinical information from consented patients and probands of different geographical backgrounds with a large dataset of genetic variants and, when available, biomarker information. An automated follow-up tool is incorporated that informs all users whenever a variant classification has changed. These unique features fully embedded in a CLIA/CAP-accredited quality management system allow appropriate data quality and enhanced patient safety. More than 100,000 genetically screened individuals are documented in the database, resulting in more than 470 million variant detections. Approximately, 57% of the clinically relevant and uncertain variants in the database are novel. Notably, 3% of the genetic variants identified and previously reported in the literature as being associated with a particular rare disease were reclassified, based on internal evidence, as clinically irrelevant. The database offers a comprehensive summary of the clinical validity and causality of detected gene variants with their associated phenotypes, and is a valuable tool

  17. Phase stable rare earth garnets

    DOEpatents

    Kuntz, Joshua D.; Cherepy, Nerine J.; Roberts, Jeffery J.; Payne, Stephen A.

    2013-06-11

    A transparent ceramic according to one embodiment includes a rare earth garnet comprising A.sub.hB.sub.iC.sub.jO.sub.12, where h is 3.+-.10%, i is 2.+-.10%, and j is 3.+-.10%. A includes a rare earth element or a mixture of rare earth elements, B includes at least one of aluminum, gallium and scandium, and C includes at least one of aluminum, gallium and scandium, where A is at a dodecahedral site of the garnet, B is at an octahedral site of the garnet, and C is at a tetrahedral site of the garnet. In one embodiment, the rare earth garment has scintillation properties. A radiation detector in one embodiment includes a transparent ceramic as described above and a photo detector optically coupled to the rare earth garnet.

  18. Rare earth gas laser

    DOEpatents

    Krupke, W.F.

    1975-10-31

    A high energy gas laser with light output in the infrared or visible region of the spectrum is described. Laser action is obtained by generating vapors of rare earth halides, particularly neodymium iodide or, to a lesser extent, neodymium bromide, and disposing the rare earth vapor medium in a resonant cavity at elevated temperatures; e.g., approximately 1200/sup 0/ to 1400/sup 0/K. A particularly preferred gaseous medium is one involving a complex of aluminum chloride and neodymium chloride, which exhibits tremendously enhanced vapor pressure compared to the rare earth halides per se, and provides comparable increases in stored energy densities.

  19. Selective Emitter Pumped Rare Earth Laser

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L. (Inventor); Patton, Martin O. (Inventor)

    2001-01-01

    A selective emitter pumped rare earth laser provides an additional type of laser for use in many laser applications. Rare earth doped lasers exist which are pumped with flashtubes or laser diodes. The invention uses a rare earth emitter to transform thermal energy input to a spectral band matching the absorption band of a rare earth in the laser in order to produce lasing.

  20. 32 CFR 644.533 - Contamination discovered after return of land to owner, or sale.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Contamination discovered after return of land to owner, or sale. 644.533 Section 644.533 National Defense Department of Defense (Continued) DEPARTMENT OF... Other Contamination from Proposed Excess Land and Improvements § 644.533 Contamination discovered after...

  1. Creating a global rare disease patient registry linked to a rare diseases biorepository database: Rare Disease-HUB (RD-HUB).

    PubMed

    Rubinstein, Yaffa R; Groft, Stephen C; Bartek, Ronald; Brown, Kyle; Christensen, Ronald A; Collier, Elaine; Farber, Amy; Farmer, Jennifer; Ferguson, John H; Forrest, Christopher B; Lockhart, Nicole C; McCurdy, Kate R; Moore, Helen; Pollen, Geraldine B; Richesson, Rachel; Miller, Vanessa Rangel; Hull, Sara; Vaught, Jim

    2010-09-01

    A movement to create a global patient registry for as many as 7,000 rare diseases was launched at a workshop, "Advancing Rare Disease Research: The Intersection of Patient Registries, Biospecimen Repositories, and Clinical Data." http://rarediseases.info.nih.gov/PATIENT_REGISTRIES_WORKSHOP/. The workshop was sponsored by the Office of Rare Diseases Research (ORDR). The focus was the building of an infrastructure for an internet-based global registry linking to biorepositories. Such a registry would serve the patients, investigators, and drug companies. To aid researchers the participants suggested the creation of a centralized database of biorepositories for rare biospecimens (RD-HUB)http://biospecimens.ordr.info.nih.gov/ that could be linked to the registry. Over two days of presentations and breakout sessions, several hundred attendees discussed government rules and regulations concerning privacy and patients' rights and the nature and scope of data to be entered into a central registry as well as concerns about how to validate patient and clinician-entered data to ensure data accuracy. Mechanisms for aggregating data from existing registries were also discussed. The attendees identified registry best practices, model coding systems, international systems for recruiting patients into clinical trials and novel ways of using the internet directly to invite participation in research. They also speculated about who would bear ultimate responsibility for the informatics in the registry and who would have access to the information. Hurdles associated with biospecimen collection and how to overcome them were detailed. The development of the recommendations was, in itself, an indication of the commitment of the rare disease community as never before. Published by Elsevier Inc.

  2. Rare earth element and rare metal inventory of central Asia

    USGS Publications Warehouse

    Mihalasky, Mark J.; Tucker, Robert D.; Renaud, Karine; Verstraeten, Ingrid M.

    2018-03-06

    Rare earth elements (REE), with their unique physical and chemical properties, are an essential part of modern living. REE have enabled development and manufacture of high-performance materials, processes, and electronic technologies commonly used today in computing and communications, clean energy and transportation, medical treatment and health care, glass and ceramics, aerospace and defense, and metallurgy and chemical refining. Central Asia is an emerging REE and rare metals (RM) producing region. A newly compiled inventory of REE-RM-bearing mineral occurrences and delineation of areas-of-interest indicate this region may have considerable undiscovered resources.

  3. DoEstRare: A statistical test to identify local enrichments in rare genomic variants associated with disease.

    PubMed

    Persyn, Elodie; Karakachoff, Matilde; Le Scouarnec, Solena; Le Clézio, Camille; Campion, Dominique; Consortium, French Exome; Schott, Jean-Jacques; Redon, Richard; Bellanger, Lise; Dina, Christian

    2017-01-01

    Next-generation sequencing technologies made it possible to assay the effect of rare variants on complex diseases. As an extension of the "common disease-common variant" paradigm, rare variant studies are necessary to get a more complete insight into the genetic architecture of human traits. Association studies of these rare variations show new challenges in terms of statistical analysis. Due to their low frequency, rare variants must be tested by groups. This approach is then hindered by the fact that an unknown proportion of the variants could be neutral. The risk level of a rare variation may be determined by its impact but also by its position in the protein sequence. More generally, the molecular mechanisms underlying the disease architecture may involve specific protein domains or inter-genic regulatory regions. While a large variety of methods are optimizing functionality weights for each single marker, few evaluate variant position differences between cases and controls. Here, we propose a test called DoEstRare, which aims to simultaneously detect clusters of disease risk variants and global allele frequency differences in genomic regions. This test estimates, for cases and controls, variant position densities in the genetic region by a kernel method, weighted by a function of allele frequencies. We compared DoEstRare with previously published strategies through simulation studies as well as re-analysis of real datasets. Based on simulation under various scenarios, DoEstRare was the sole to consistently show highest performance, in terms of type I error and power both when variants were clustered or not. DoEstRare was also applied to Brugada syndrome and early-onset Alzheimer's disease data and provided complementary results to other existing tests. DoEstRare, by integrating variant position information, gives new opportunities to explain disease susceptibility. DoEstRare is implemented in a user-friendly R package.

  4. Discovering drugs for the treatment of Ebola virus

    DTIC Science & Technology

    2017-08-04

    Discovering drugs for the treatment of Ebola virus Sandra L. Bixler, Allen J. Duplantier and Sina Bavari Address United States Army Medical...with the recent West African outbreak resulting in over 11,000 deaths. This review provides a summary of the status of drug discovery and development...disease, including small molecules, immunotherapeutics, host factors, and clinical disease management options. Introduction Drug development for

  5. Discover Summer School: Evaluation Report and Executive Summary

    ERIC Educational Resources Information Center

    Torgerson, David; Torgerson, Carole; Jefferson, Laura; Buckley, Hannah; Ainsworth, Hannah; Heaps, Clare; Mitchell, Natasha

    2014-01-01

    The Discover Summer School was a four-week programme which aimed to improve the reading and writing skills of children during the summer between Year 6 and Year 7. The programme was targeted at pupils who had been predicted to achieve below Level 4b in English by the end of Key Stage 2. Pupils meeting the eligibility criteria for the study, and…

  6. Re-discovering ancient wheat varieties as functional foods.

    PubMed

    Cooper, Raymond

    2015-07-01

    With the gluten-free food market worth almost $1.6 bn in 2011, there is every reason for renewed interest in ancient grains. This resurgent interest is expressed in re-discovering ancient varieties as functional foods. In particular, people affected by celiac disease have to avoid all gluten in their diet and several ancient grains may offer an important alternative.

  7. Re-Discovering Mendel: The Case of Carl Correns

    ERIC Educational Resources Information Center

    Rheinberger, Hans-Jörg

    2015-01-01

    Carl Erich Correns (1864-1933) is remembered in the annals of science as one of the three botanists who re-discovered Mendel's laws. He can also, however, be regarded as one of the founding figures of classical genetics in Germany. Between 1894 and 1899 he carried out the crossing experiments with corn and peas that led to the re-statement of…

  8. The Use of a Performance Assessment for Identifying Gifted Lebanese Students: Is DISCOVER Effective?

    ERIC Educational Resources Information Center

    Sarouphim, Ketty M.

    2009-01-01

    The purpose of this study was to investigate the effectiveness of DISCOVER, a performance- based assessment in identifying gifted Lebanese students. The sample consisted of 248 students (121 boys, 127 girls) from Grades 3-5 at two private schools in Beirut, Lebanon. Students were administered DISCOVER and the Raven Standard Progressive Matrices…

  9. Production method for making rare earth compounds

    DOEpatents

    McCallum, R.W.; Ellis, T.W.; Dennis, K.W.; Hofer, R.J.; Branagan, D.J.

    1997-11-25

    A method of making a rare earth compound, such as a earth-transition metal permanent magnet compound, without the need for producing rare earth metal as a process step, comprises carbothermically reacting a rare earth oxide to form a rare earth carbide and heating the rare earth carbide, a compound-forming reactant (e.g., a transition metal and optional boron), and a carbide-forming element (e.g., a refractory metal) that forms a carbide that is more thermodynamically favorable than the rare earth carbide whereby the rare earth compound (e.g., Nd{sub 2}Fe{sub 14}B or LaNi{sub 5}) and a carbide of the carbide-forming element are formed.

  10. Production method for making rare earth compounds

    DOEpatents

    McCallum, R. William; Ellis, Timothy W.; Dennis, Kevin W.; Hofer, Robert J.; Branagan, Daniel J.

    1997-11-25

    A method of making a rare earth compound, such as a earth-transition metal permanent magnet compound, without the need for producing rare earth metal as a process step, comprises carbothermically reacting a rare earth oxide to form a rare earth carbide and heating the rare earth carbide, a compound-forming reactant (e.g. a transition metal and optional boron), and a carbide-forming element (e.g. a refractory metal) that forms a carbide that is more thermodynamically favorable than the rare earth carbide whereby the rare earth compound (e.g. Nd.sub.2 Fe.sub.14 B or LaNi.sub.5) and a carbide of the carbide-forming element are formed.

  11. Screening individual hybridomas by microengraving to discover monoclonal antibodies

    PubMed Central

    Ogunniyi, Adebola O; Story, Craig M; Papa, Eliseo; Guillen, Eduardo; Love, J Christopher

    2014-01-01

    The demand for monoclonal antibodies (mAbs) in biomedical research is significant, but the current methodologies used to discover them are both lengthy and costly. Consequently, the diversity of antibodies available for any particular antigen remains limited. Microengraving is a soft lithographic technique that provides a rapid and efficient alternative for discovering new mAbs. This protocol describes how to use microengraving to screen mouse hybridomas to establish new cell lines producing unique mAbs. Single cells from a polyclonal population are isolated into an array of microscale wells (~105 cells per screen). The array is then used to print a protein microarray, where each element contains the antibodies captured from individual wells. The antibodies on the microarray are screened with antigens of interest, and mapped to the corresponding cells, which are then recovered from their microwells by micromanipulation. Screening and retrieval require approximately 1–3 d (9–12 d including the steps for preparing arrays of microwells). PMID:19528952

  12. Competing Structural Instabilities in the Ruddlesden–Popper Derivatives HRTiO 4 (R = Rare Earths): Oxygen Octahedral Rotations Inducing Noncentrosymmetricity and Layer Sliding Retaining Centrosymmetricity

    DOE PAGES

    Sen Gupta, Arnab; Akamatsu, Hirofumi; Brown, Forrest G.; ...

    2016-12-06

    We report the discovery of noncentrosymmetry in the family of HRTiO 4 (R = Eu, Gd, Dy) layered oxides possessing a Ruddlesden-Popper derivative structure, by second harmonic generation and synchrotron x-ray diffraction with the support of density functional theory calculations. These oxides were previously thought to possess inversion symmetry. Here, inversion symmetry is broken by oxygen octahedral rotations, a mechanism that is not active in simple perovskites. We discover a competition between oxygen octahedral rotations and sliding of the octahedral perovskite blocks at the OH layers. For the smaller rare earth ions, R = Eu, Gd, Dy, which favor themore » octahedral rotations, noncentrosymmetry is present but the sliding at the OH layer is absent. For the larger rare earth ions, R = Nd and Sm, the octahe-dral rotations are absent, but sliding of the octahedral blocks at the OH layer is present, likely to optimize the hydrogen bond length arising from the directional nature of these bonds in the crystal structure. The study reveals a new mechanism for inducing noncentrosymmetry in layered oxides, and chemical-structural effects related to rare earth ion size and hydrogen bonding that can turn this mechanism on and off. In conclusion, we construct a complete phase diagram of temperature versus rare earth ionic radius for the HRTiO 4 family.« less

  13. Competing Structural Instabilities in the Ruddlesden–Popper Derivatives HRTiO 4 (R = Rare Earths): Oxygen Octahedral Rotations Inducing Noncentrosymmetricity and Layer Sliding Retaining Centrosymmetricity

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

    Sen Gupta, Arnab; Akamatsu, Hirofumi; Brown, Forrest G.

    We report the discovery of noncentrosymmetry in the family of HRTiO 4 (R = Eu, Gd, Dy) layered oxides possessing a Ruddlesden-Popper derivative structure, by second harmonic generation and synchrotron x-ray diffraction with the support of density functional theory calculations. These oxides were previously thought to possess inversion symmetry. Here, inversion symmetry is broken by oxygen octahedral rotations, a mechanism that is not active in simple perovskites. We discover a competition between oxygen octahedral rotations and sliding of the octahedral perovskite blocks at the OH layers. For the smaller rare earth ions, R = Eu, Gd, Dy, which favor themore » octahedral rotations, noncentrosymmetry is present but the sliding at the OH layer is absent. For the larger rare earth ions, R = Nd and Sm, the octahe-dral rotations are absent, but sliding of the octahedral blocks at the OH layer is present, likely to optimize the hydrogen bond length arising from the directional nature of these bonds in the crystal structure. The study reveals a new mechanism for inducing noncentrosymmetry in layered oxides, and chemical-structural effects related to rare earth ion size and hydrogen bonding that can turn this mechanism on and off. In conclusion, we construct a complete phase diagram of temperature versus rare earth ionic radius for the HRTiO 4 family.« less

  14. Astronomers Find the First 'Wind Nebula' Around a Rare Ultra-Magnetic Neutron Star

    NASA Image and Video Library

    2016-06-21

    Astronomers have discovered a vast cloud of high-energy particles called a wind nebula around a rare ultra-magnetic neutron star, or magnetar, for the first time. The find offers a unique window into the properties, environment and outburst history of magnetars, which are the strongest magnets in the universe. A neutron star is the crushed core of a massive star that ran out of fuel, collapsed under its own weight, and exploded as a supernova. Each one compresses the equivalent mass of half a million Earths into a ball just 12 miles (20 kilometers) across, or about the length of New York's Manhattan Island. Neutron stars are most commonly found as pulsars, which produce radio, visible light, X-rays and gamma rays at various locations in their surrounding magnetic fields. When a pulsar spins these regions in our direction, astronomers detect pulses of emission, hence the name. Credit: ESA/XMM-Newton/Younes et al. 2016

  15. A rare case of osteoma in the frontal sinus: anatomical and histological description.

    PubMed

    Funieru, Cristian; Bănică, Bogdan; Cumpătă, Cristian-Niky; Sfeatcu, Ruxandra Ionela; Dumitrache, Adina Mihaela; Răescu, Mihaela; Dascălu, Ionela Teodora; Simion, George; Ţuculină, Mihaela Jana

    2014-01-01

    The purpose of this paper is to present a rare case of osteoma localized in the left frontal sinus. A 22-year-old woman who arrived at the Department of Neurosurgery of the University Emergency Hospital, Bucharest, Romania, presented a vertical asymmetry of the eyeballs but displayed no clinical signs like pain or diplopia. The computer tomography exam was used for preoperatory diagnostic. Histopathology was performed after surgery using Hematoxylin and Eosin staining. The Nikon Eclipse microscope was used to examine the slides. The histopathology exam shows a compact osteoma with dense and non-Haversian bone tissue and parallel bony trabeculae. A few spaces for the marrow were also found. The osteocytes were small and no fibrous cells were discovered. The computer tomography and histopathology exam were the investigations that lead us to a true diagnostic of dense osteoma. This tumor was the first case of frontal sinus osteoma histologically described in the Romanian population.

  16. Rare earth elements: end use and recyclability

    USGS Publications Warehouse

    Goonan, Thomas G.

    2011-01-01

    Rare earth elements are used in mature markets (such as catalysts, glassmaking, lighting, and metallurgy), which account for 59 percent of the total worldwide consumption of rare earth elements, and in newer, high-growth markets (such as battery alloys, ceramics, and permanent magnets), which account for 41 percent of the total worldwide consumption of rare earth elements. In mature market segments, lanthanum and cerium constitute about 80 percent of rare earth elements used, and in new market segments, dysprosium, neodymium, and praseodymium account for about 85 percent of rare earth elements used. Regardless of the end use, rare earth elements are not recycled in large quantities, but could be if recycling became mandated or very high prices of rare earth elements made recycling feasible.

  17. Mouse Models of Rare Craniofacial Disorders.

    PubMed

    Achilleos, Annita; Trainor, Paul A

    2015-01-01

    A rare disease is defined as a condition that affects less than 1 in 2000 individuals. Currently more than 7000 rare diseases have been documented, and most are thought to be of genetic origin. Rare diseases primarily affect children, and congenital craniofacial syndromes and disorders constitute a significant proportion of rare diseases, with over 700 having been described to date. Modeling craniofacial disorders in animal models has been instrumental in uncovering the etiology and pathogenesis of numerous conditions and in some cases has even led to potential therapeutic avenues for their prevention. In this chapter, we focus primarily on two general classes of rare disorders, ribosomopathies and ciliopathies, and the surprising finding that the disruption of fundamental, global processes can result in tissue-specific craniofacial defects. In addition, we discuss recent advances in understanding the pathogenesis of an extremely rare and specific craniofacial condition known as syngnathia, based on the first mouse models for this condition. Approximately 1% of all babies are born with a minor or major developmental anomaly, and individuals suffering from rare diseases deserve the same quality of treatment and care and attention to their disease as other patients. © 2015 Elsevier Inc. All rights reserved.

  18. Rare variants and autoimmune disease.

    PubMed

    Massey, Jonathan; Eyre, Steve

    2014-09-01

    The study of rare variants in monogenic forms of autoimmune disease has offered insight into the aetiology of more complex pathologies. Research in complex autoimmune disease initially focused on sequencing candidate genes, with some early successes, notably in uncovering low-frequency variation associated with Type 1 diabetes mellitus. However, other early examples have proved difficult to replicate, and a recent study across six autoimmune diseases, re-sequencing 25 autoimmune disease-associated genes in large sample sizes, failed to find any associated rare variants. The study of rare and low-frequency variation in autoimmune diseases has been made accessible by the inclusion of such variants on custom genotyping arrays (e.g. Immunochip and Exome arrays). Whole-exome sequencing approaches are now also being utilised to uncover the contribution of rare coding variants to disease susceptibility, severity and treatment response. Other sequencing strategies are starting to uncover the role of regulatory rare variation. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Photographs and Committees: Activities That Help Students Discover Permutations and Combinations.

    ERIC Educational Resources Information Center

    Szydlik, Jennifer Earles

    2000-01-01

    Presents problem situations that support students when discovering the multiplication principle, permutations, combinations, Pascal's triangle, and relationships among those objects in a concrete context. (ASK)

  20. 75 FR 47458 - TRICARE; Rare Diseases Definition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... TRICARE; Rare Diseases Definition AGENCY: Office of the Secretary, DoD. ACTION: Final rule. SUMMARY: This final rule revises the definition of rare diseases to adopt the definition of a rare disease as promulgated by the National Institutes of Health, Office of Rare Diseases. The rule modification will result...

  1. Bayesian analysis of rare events

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

    Straub, Daniel, E-mail: straub@tum.de; Papaioannou, Iason; Betz, Wolfgang

    2016-06-01

    In many areas of engineering and science there is an interest in predicting the probability of rare events, in particular in applications related to safety and security. Increasingly, such predictions are made through computer models of physical systems in an uncertainty quantification framework. Additionally, with advances in IT, monitoring and sensor technology, an increasing amount of data on the performance of the systems is collected. This data can be used to reduce uncertainty, improve the probability estimates and consequently enhance the management of rare events and associated risks. Bayesian analysis is the ideal method to include the data into themore » probabilistic model. It ensures a consistent probabilistic treatment of uncertainty, which is central in the prediction of rare events, where extrapolation from the domain of observation is common. We present a framework for performing Bayesian updating of rare event probabilities, termed BUS. It is based on a reinterpretation of the classical rejection-sampling approach to Bayesian analysis, which enables the use of established methods for estimating probabilities of rare events. By drawing upon these methods, the framework makes use of their computational efficiency. These methods include the First-Order Reliability Method (FORM), tailored importance sampling (IS) methods and Subset Simulation (SuS). In this contribution, we briefly review these methods in the context of the BUS framework and investigate their applicability to Bayesian analysis of rare events in different settings. We find that, for some applications, FORM can be highly efficient and is surprisingly accurate, enabling Bayesian analysis of rare events with just a few model evaluations. In a general setting, BUS implemented through IS and SuS is more robust and flexible.« less

  2. Bayesian analysis of rare events

    NASA Astrophysics Data System (ADS)

    Straub, Daniel; Papaioannou, Iason; Betz, Wolfgang

    2016-06-01

    In many areas of engineering and science there is an interest in predicting the probability of rare events, in particular in applications related to safety and security. Increasingly, such predictions are made through computer models of physical systems in an uncertainty quantification framework. Additionally, with advances in IT, monitoring and sensor technology, an increasing amount of data on the performance of the systems is collected. This data can be used to reduce uncertainty, improve the probability estimates and consequently enhance the management of rare events and associated risks. Bayesian analysis is the ideal method to include the data into the probabilistic model. It ensures a consistent probabilistic treatment of uncertainty, which is central in the prediction of rare events, where extrapolation from the domain of observation is common. We present a framework for performing Bayesian updating of rare event probabilities, termed BUS. It is based on a reinterpretation of the classical rejection-sampling approach to Bayesian analysis, which enables the use of established methods for estimating probabilities of rare events. By drawing upon these methods, the framework makes use of their computational efficiency. These methods include the First-Order Reliability Method (FORM), tailored importance sampling (IS) methods and Subset Simulation (SuS). In this contribution, we briefly review these methods in the context of the BUS framework and investigate their applicability to Bayesian analysis of rare events in different settings. We find that, for some applications, FORM can be highly efficient and is surprisingly accurate, enabling Bayesian analysis of rare events with just a few model evaluations. In a general setting, BUS implemented through IS and SuS is more robust and flexible.

  3. Organization for rare diseases India (ORDI) - addressing the challenges and opportunities for the Indian rare diseases' community.

    PubMed

    Rajasimha, Harsha Karur; Shirol, Prasannakumar Basayya; Ramamoorthy, Preveen; Hegde, Madhuri; Barde, Sangeeta; Chandru, Vijay; Ravinandan, M E; Ramchandran, Ramani; Haldar, Kasturi; Lin, Jimmy C; Babar, Imran A; Girisha, Katta M; Srinivasan, Sudha; Navaneetham, Duraiswamy; Battu, Rajani; Devarakonda, Rajashree; Kini, Usha; Vijayachandra, Kinnimulki; Verma, Ishwar C

    2014-08-13

    In order to address the unmet needs and create opportunities that benefit patients with rare disease in India, a group of volunteers created a not-for-profit organization named Organization for Rare Diseases India (ORDI; www.ordindia.org). ORDI plans to represent the collective voice and advocate the needs of patients with rare diseases and other stakeholders in India. The ORDI team members come from diverse backgrounds such as genetics, molecular diagnostics, drug development, bioinformatics, communications, information technology, patient advocacy and public service. ORDI builds on the lessons learned from numerous similar organizations in the USA, European Union and disease-specific rare disease foundations in India. In this review, we provide a background on the landscape of rare diseases and the organizations that are active in this area globally and in India. We discuss the unique challenges in tackling rare diseases in India, and highlight the unmet needs of the key stakeholders of rare diseases. Finally, we define the vision, mission, goals and objectives of ORDI, identify the key developments in the health care context in India and welcome community feedback and comments on our approach.

  4. Yes, Aboriginal Australians can and did discover the variability of Betelgeuse

    NASA Astrophysics Data System (ADS)

    Schaefer, Bradley E.

    2018-04-01

    Recently, a widely publicized claim has been made that the Aboriginal Australians discovered the variability of the red star Betelgeuse in the modern Orion, plus the variability of two other prominent red stars: Aldebaran and Antares. This result has excited the usual healthy skepticism, with questions about whether any untrained peoples can discover the variability and whether such a discovery is likely to be placed into lore and transmitted for long periods of time. Here, I am offering an independent evaluation, based on broad experience with naked-eye sky viewing and astro-history. I find that it is easy for inexperienced observers to detect the variability of Betelgeuse over its range in brightness from V = 0.0 to V = 1.3, for example in noticing from season-to-season that the star varies from significantly brighter than Procyon to being greatly fainter than Procyon. Further, indigenous peoples in the Southern Hemisphere inevitably kept watch on the prominent red star, so it is inevitable that the variability of Betelgeuse was discovered many times over during the last 65 millennia. The processes of placing this discovery into a cultural context (in this case, put into morality stories) and the faithful transmission for many millennia is confidently known for the Aboriginal Australians in particular. So this shows that the whole claim for a changing Betelgeuse in the Aboriginal Australian lore is both plausible and likely. Given that the discovery and transmission is easily possible, the real proof is that the Aboriginal lore gives an unambiguous statement that these stars do indeed vary in brightness, as collected by many ethnographers over a century ago from many Aboriginal groups. So I strongly conclude that the Aboriginal Australians could and did discover the variability of Betelgeuse, Aldebaran, and Antares.

  5. Progress Towards Left-Handed Electromagnetic Waves in Rare-Earth Doped Crystals

    NASA Astrophysics Data System (ADS)

    Brewer, Nicholas Riley

    In 1968 Victor Veselago determined that a material with both a negative permittivity and negative permeability would have some extraordinary properties. The index of refraction of this material would be negative and light propagating inside would be 'left-handed'. This research went relatively unnoticed until the year 2000 when John Pendry discovered that a lens with an index of refraction of n = -1 could, in principle, have infinite resolution. Since 2000, research into negative index materials has exploded. The challenging part of this research is to get a material to respond to magnetic fields at optical frequencies. Artificially created metamaterials are able to achieve this and have been the focus of most negative index research. The long term goal of our project is to produce left-handed light in an atomic system. In order to do this, an atomic transition needs to be utilized that is magnetic dipole in character. Pure magnetic dipole transitions in the optical regime are more rare and fundamentally much weaker than the electric dipole transitions typically used in atomic physics experiments. They can be found, however, in the complex atomic structure of rare-earth elements. The 7F0 → 5D 1 transition in europium doped yttrium orthosilicate (Eu3+:Y 2SiO5) has a wavelength of 527.5 nm and is a pure magnetic dipole transition. We measured its dipole moment to be (0.063 +/- 0.005)mu B via Rabi oscillations, inferring a magnetization on the order of 10 -2 A/m. Demonstrating this large magnetic response at an optical frequency is a major first step in realizing left-handed light in atomic systems.

  6. Recovering heavy rare earth metals from magnet scrap

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

    Ott, Ryan T.; McCallum, Ralph W.; Jones, Lawrence L.

    A method of treating rare earth metal-bearing permanent magnet scrap, waste or other material in a manner to recover the heavy rare earth metal content separately from the light rare earth metal content. The heavy rare earth metal content can be recovered either as a heavy rare earth metal-enriched iron based alloy or as a heavy rare earth metal based alloy.

  7. ToO observations of a newly discovered interstellar ('Oumuamua-like) object

    NASA Astrophysics Data System (ADS)

    Trilling, David; Hora, Joseph; Mommert, Michael; Farnocchia, Davide; Chesley, Steve; Emery, Joshua; Fazio, Giovanni; Harris, Alan; Mueller, Migo; Smith, Howard

    2018-05-01

    We propose a Target of Opportunity (ToO) program to observe a newly discovered interstellar asteroid. This program is modeled on our DDT observations of 'Oumuamua. We will only trigger this ToO observation if an object is discovered with sufficient lead time to be scheduled for Spitzer observations; if the object will be within the Spitzer observability cone; and if the object is likely to be bright enough to be detected. From the proposed observations we will measure the diameter and albedo of the object - likely the only way that either of those properties will be determined. The result will provide a critical second data point for studies of planetary system formation as traced by these interstellar interlopers.

  8. Spectroscopic Classifications with Magellan of 7 Supernovae Discovered by DES

    NASA Astrophysics Data System (ADS)

    Blanchard, P. K.; Challis, P.; Drout, M.; Kirshner, R.; Brown, P. J.; Krisciunas, K.; Suntzeff, N.; D'Andrea, C.; Nichol, R.; Papadopoulos, A.; Smith, M.; Sullivan, M.; Maartens, R.; Gupta, R.; Kovacs, E.; Kuhlmann, S.; Spinka, H.; Ahn, E.; Finley, D. A.; Frieman, J.; Marriner, J.; Wester, W.; Aldering, G.; Kim, A. G.; Thomas, R. C.; Barbary, K.; Bloom, J. S.; Goldstein, D.; Nugent, P.; Perlmutter, S.; Foley, R. J.; Castander, F. J.; Desai, S.; Paech, K.; Smith, R. C.; Schubnell, M.; Kessler, R.; Scolnic, D.; Covarrubias, R. A.; Brout, D. J.; Fischer, J. A.; Gladney, L.; March, M.; Sako, M.; Wolf, R. C.

    2015-01-01

    We report optical spectroscopy of supernova candidates discovered by the Dark Energy Survey. The spectra (425-945 nm) were obtained using IMACS on the 6.5m Baade telescope at the Las Campanas Observatory on Dec 19, 2014.

  9. [SZCZECIN CITIZENS' KNOWLEDGE ABOUT RARE DISEASES].

    PubMed

    Walat, Anna; Skoczylas, Michal Marian; Welnicka, Agnieszka; Kulig, Malgorzata; Rodak, Przemyslaw; Walczak, Zuzanna; Jablońska, Agata

    2014-01-01

    The aim of the study was to assess knowledge about rare diseases among citizens of Szczecin (Poland). The study was performed by questioning 242 adult customers of Turzyn Shopping Centre in Szczecin (149 females and 93 males). The survey was conducted in the shopping mall on 23 February 2013 (control group) and during the celebration of Rare Disease Day and the 12th Polish Nationwide Cystic Fibrosis Week ("Dolina Mukolinków") on 2 March 2013 (research group). The research tool was a questionnaire devised by the authors and filled out by the writing authors interviewer's answers. In the study group more people knew about the existence of Rare Disease Day than in the control group (86.02% vs 57.72%, chi-square test χ2 > χ2(1); 0.001, p < 0.001), but there was no significant difference between knowledge of when Rare Disease Day is celebrated. The definition of rare diseases compatible with the definition of the European Commission's Health and Consumer Protection was reported only in the control group by 4 people. Examples of rare diseases were reported by 74.19% of the respondents in the study group and by 65.10% in the control group (more than 130 diseases were mentioned altogether). Usually, respondents mentioned fewer examples than were asked about in the questionnaire. The aim of Rare Disease Day was accurately specified by 86.02% of persons in the study group and 87.92% in the control group. Rare Disease Day personally concerns 30.11% of respondents in the study group and 10.07% of persons in the control group (OR = 3.85, 95% CI 0.9-3.6, χ2 > χ2(1); 0.001, p < 0.001). The respondents from the research group knew more about Rare Disease Day and defined the idea of it as closed in a significantly higher degree than the control group. There was no significant difference in the detailed knowledge about rare diseases in either group. This might indicate the need to educate society and patients, along with their families.

  10. A Rare Reason of Hyperinsulinism: Munchausen Syndrome by Proxy.

    PubMed

    Akın, Onur; Yeşilkaya, Ediz; Sari, Erkan; Akar, Çağdaş; Başbozkurt, Gökalp; Macit, Enis; Aydin, Ibrahim; Taşlipinar, Abdullah; Gül, Hüsamettin

    2016-01-01

    Hyperinsulinism, one of the most important causes of hypoglycaemia, can be congenital or acquired. Rarely, drug toxicity can be a reason for hyperinsulinism. In the context of Munchausen syndrome by proxy (MSP), toxicity usually occurs in children due to drug administration by a parent or caregiver. A 7-year-old girl was referred to our department due to a hyperglycaemic period and hypoglycaemic episodes. On admission, gliclazide was initiated due to her hyperglycaemia, which we attributed to maturity onset diabetes of the young. However, during follow-up, hypoglycaemic levels were detected. Despite cessation of gliclazide, hypoglycaemic seizures occurred. Even with the medications administered, hypoglycaemia could not be prevented. During follow-up, the mother's affect, characterized by anxiety and interest in her daughter's medical care, appeared discordant with the situation. Due to our suspicion of MSP, we discovered toxic levels of gliclazide in the blood and urine samples which had been sent to the toxicology laboratory to search for hypoglycaemic agents. The patient was isolated, and all medications were stopped. After isolation, her hypoglycaemia disappeared, and she became hyperglycaemic (250 mg/dl). Physicians should consider the possibility of MSP in hyperinsulinaemic patients with discordant laboratory results and clinical symptoms, even if the child's parents display great concern. © 2016 S. Karger AG, Basel.

  11. Rare essentials: drugs for rare diseases as essential medicines.

    PubMed

    Stolk, Pieter; Willemen, Marjolein J C; Leufkens, Hubert G M

    2006-09-01

    Since 1977, the WHO Model List of Essential Medicines (EML), published by WHO, has provided advice for Member States that struggle to decide which pharmaceutical technologies should be provided to patients within their public health systems. Originating from outside WHO, an incentive system has been put in place by various governments for the development of medicines for rare diseases ("orphan drugs"). With progress in pharmaceutical research (e.g. drugs targeted for narrower indications), these medicines will feature more often on future public health agendas. However, when current definitions for selecting essential medicines are applied strictly, orphan drugs cannot be part of the WHO Essential Medicines Programme, creating the risk that WHO may lose touch with this field. In our opinion WHO should explicitly include orphan drugs in its policy sphere by composing a complementary Orphan Medicines Model List as an addition to the EML. This complementary list of "rare essentials" could aid policy-makers and patients in, for example, emerging countries to improve access to these drugs and stimulate relevant policies. Furthermore, inconsistencies in the current EML with regard to medicines for rare diseases can be resolved. In this paper we propose selection criteria for an Orphan Medicines Model List that could form a departure point for future work towards an extensive WHO Orphan Medicines Programme.

  12. Rare essentials: drugs for rare diseases as essential medicines.

    PubMed Central

    Stolk, Pieter; Willemen, Marjolein J. C.; Leufkens, Hubert G. M.

    2006-01-01

    Since 1977, the WHO Model List of Essential Medicines (EML), published by WHO, has provided advice for Member States that struggle to decide which pharmaceutical technologies should be provided to patients within their public health systems. Originating from outside WHO, an incentive system has been put in place by various governments for the development of medicines for rare diseases ("orphan drugs"). With progress in pharmaceutical research (e.g. drugs targeted for narrower indications), these medicines will feature more often on future public health agendas. However, when current definitions for selecting essential medicines are applied strictly, orphan drugs cannot be part of the WHO Essential Medicines Programme, creating the risk that WHO may lose touch with this field. In our opinion WHO should explicitly include orphan drugs in its policy sphere by composing a complementary Orphan Medicines Model List as an addition to the EML. This complementary list of "rare essentials" could aid policy-makers and patients in, for example, emerging countries to improve access to these drugs and stimulate relevant policies. Furthermore, inconsistencies in the current EML with regard to medicines for rare diseases can be resolved. In this paper we propose selection criteria for an Orphan Medicines Model List that could form a departure point for future work towards an extensive WHO Orphan Medicines Programme. PMID:17128345

  13. Twenty-First Century Diseases: Commonly Rare and Rarely Common?

    PubMed

    Daunert, Sylvia; Sittampalam, Gurusingham Sitta; Goldschmidt-Clermont, Pascal J

    2017-09-20

    Alzheimer's drugs are failing at a rate of 99.6%, and success rate for drugs designed to help patients with this form of dementia is 47 times less than for drugs designed to help patients with cancers ( www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/2014 ). How can it be so difficult to produce a valuable drug for Alzheimer's disease? Each human has a unique genetic and epigenetic makeup, thus endowing individuals with a highly unique complement of genes, polymorphisms, mutations, RNAs, proteins, lipids, and complex sugars, resulting in distinct genome, proteome, metabolome, and also microbiome identity. This editorial is taking into account the uniqueness of each individual and surrounding environment, and stresses the point that a more accurate definition of a "common" disorder could be simply the amalgamation of a myriad of "rare" diseases. These rare diseases are being grouped together because they share a rather constant complement of common features and, indeed, generally respond to empirically developed treatments, leading to a positive outcome consistently. We make the case that it is highly unlikely that such treatments, despite their statistical success measured with large cohorts using standardized clinical research, will be effective on all patients until we increase the depth and fidelity of our understanding of the individual "rare" diseases that are grouped together in the "buckets" of common illnesses. Antioxid. Redox Signal. 27, 511-516.

  14. New hot spot on Io discovered by NIMS during orbit C9

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Near-Infrared Mapping Spectrometer (NIMS) on Galileo observes Io on nearly every orbit as part of a program monitoring the level of volcanic activity on this moon. Io is the most volcanically active body in the Solar System and NIMS has discovered many new volcanoes. The latest addition to the inventory was discovered during orbit C9, at Shamash Patera, located on the side of Io facing away from Jupiter. The image above shows, on the left, the portion of Io imaged during this observation as seen by Voyager. The image on the right shows Io at 4.99 microns (in the infrared). Some of the disk is in darkness, making the identification of these hot spots easier. New names have been given to some of the newly discovered features. The hot spots Isum, Mulungu and Tupan have been active since their discovery during the G1 orbit. Zamama, an active region between Prometheus and Isum, was discovered during G1. It was active through orbit E4 but has since faded considerably.

    This image was taken on June 28, 1997, at a resolution of 302 km/pixel.

    The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.

    The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.

    This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov.

  15. Rare Earth Element Mines, Deposits, and Occurrences

    USGS Publications Warehouse

    Orris, Greta J.; Grauch, Richard I.

    2002-01-01

    Data on rare earth (including yttrium) mines, deposits, and occurrences were compiled as part of an effort by the USGS and the University of Arizona Center for Mineral Resources to summarize current knowledge on the supply and demand outlook and related topics for this group of elements. Economic competition and environmental concerns are increasingly constraining the mining and processing of rare earths from the Mountain Pass mine in California. For many years, the deposit at Mountain Pass was the world's dominant source of rare earth elements and the United States was essentially self-sufficient. Starting approximately 10 years ago, the U.S. has become increasingly dependent (> 90 percent of separated rare earths) upon imports from China, now the dominant source of rare earths. A knowledge of the known economic and noneconomic sources of rare earths is basic to evaluating the outlook for rare earth supply and associated issues.

  16. Economic aspects of rare diseases.

    PubMed

    Borski, Krzysztof

    2015-01-01

    Economic problems related to the prevention, diagnosis and treatment of rare diseases are presented paying particular attention to the costs of financing treatment, including the issue of its refund, which is a fundamental and difficult to solve economic problem of the health care system. Rare diseases, despite the low frequency of occurrence, together cover a large group of diseases being a serious medical, social and economic problem. The adoption of Polish National Plan for Rare Diseases resulting from the recommendations of the Council of the European Union, the extension of institutional activities related to the area of public health and social initiatives seeking innovative solutions to create a model of social support for patients and their families, with very high complexity of the issues regarding rare diseases, results in the need for a coherent, comprehensive, system operations and adoption of comprehensive solutions.

  17. Discovering Communicable Models from Earth Science Data

    NASA Technical Reports Server (NTRS)

    Schwabacher, Mark; Langley, Pat; Potter, Christopher; Klooster, Steven; Torregrosa, Alicia

    2002-01-01

    This chapter describes how we used regression rules to improve upon results previously published in the Earth science literature. In such a scientific application of machine learning, it is crucially important for the learned models to be understandable and communicable. We recount how we selected a learning algorithm to maximize communicability, and then describe two visualization techniques that we developed to aid in understanding the model by exploiting the spatial nature of the data. We also report how evaluating the learned models across time let us discover an error in the data.

  18. Rare Earths; The Fraternal Fifteen (Rev.)

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

    Gschneidner, Jr., Karl A.

    1966-01-01

    Rare earths are a set of 15 elements: lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium and lutetium. They are not rare and not earths; they are metals and quite abundant. They are studied to develop commercial products which are beneficial to mankind, and because some rare earths are important to fission products.

  19. Mineral resource of the month: rare earth elements

    USGS Publications Warehouse

    ,

    2011-01-01

    The article provides information on rare earth elements, which are group of 17 natural metallic elements. The rare earth elements are scandium, yttrium and lanthanides and classified into light rare earth elements (LREE) and heavy rate earth elements (HREE). The principal ores of the rare earth elements are identified. An overview of China's production of 97 percent of the rare earths in the world is provided. Commercial applications of rare earths are described.

  20. (4015) 1979 VA: 'Missing Link' Discovered

    NASA Technical Reports Server (NTRS)

    Helin, Eleanor F.

    1993-01-01

    Apollo Asteroid (4015) 1979 VA was discovered in November of 1979 by Helin at Palomar with the 0.46m Schmidt Telescope. It's orbital elements immediately indicated a possible cometary origin. With an extremely eccentric orbit, it approaches the orbit of Jupiter (at the time, the largest 'Q', aphelion, of any known near-Earth asteroid). Physical observations acquired during the discovery apparition suggested that it was carbonaceous in nature. Research into prediscovery observations of Near-Earth Asteroids (Bowell et. al., 1992) has located Palomar Sky Survey photographic plates taken in 1949 observations of (4015) 1979 VA, not as an asteroid, but rather a small cometary image (IAU Circular Nos. 5585 and 5586, August 13, 1992)...

  1. Discovering network behind infectious disease outbreak

    NASA Astrophysics Data System (ADS)

    Maeno, Yoshiharu

    2010-11-01

    Stochasticity and spatial heterogeneity are of great interest recently in studying the spread of an infectious disease. The presented method solves an inverse problem to discover the effectively decisive topology of a heterogeneous network and reveal the transmission parameters which govern the stochastic spreads over the network from a dataset on an infectious disease outbreak in the early growth phase. Populations in a combination of epidemiological compartment models and a meta-population network model are described by stochastic differential equations. Probability density functions are derived from the equations and used for the maximal likelihood estimation of the topology and parameters. The method is tested with computationally synthesized datasets and the WHO dataset on the SARS outbreak.

  2. [Branchiogen cyst at unusual age and in rare localization. A case report].

    PubMed

    Horvath, Dóra; Redl, Pál; Hegedűs, Csaba

    2015-12-01

    Branchiogen anomalies represent a heterogeneous group of developmental abnormalities, they arise from incomplete obliteration of branchial clefts and pouches during embriogenesis. Clinically they can present as a cyst, fistula or sinus. Second cleft lesions account for 95% of the branchial anomalies. Second branchial cleft cysts are usually located in the neck, along the anterior border of the stenocleidomastoid muscle, but they can be anywhere along the course of the second branchial fistula from the tonsillar fossa to the supraclavicular region. Their presence in the nasopharynx is extremely rare. Ultrasound, computed tomography (CT) or magnetic resonance imaging is recommended for diagnosis. Definitive treatment is surgical excision, these lesions do not regress spontaneously and often result recurrent infections. A 7 month old infant applied to a pediatrician with gastrointestinal viral infection. During examination a cystic mass was discovered in the right lateral nasopharyngeal wall, the lesion extended to the oropharynx. Marsupialisation was performed via transoral approach. In case of cystic lesion in the lateral epipharynx, branchial cleft cyst should be considered in the differential diagnosis.

  3. The Rare Earth Magnet Industry and Rare Earth Price in China

    NASA Astrophysics Data System (ADS)

    Ding, Kaihong

    2014-07-01

    In the past four years, the price of rare earth metal fluctuates sharply for many reasons. Currently, it has become more stable and more reasonable. This presentation is focused on the effect about the rare earth metal price. Some motor manufacturers have shifted from rare earth permanent magnet to ferrite magnet. Many motor manufacturers changed the design for the motor cooling system to make the motor function at a lower temperature. Thus the consumption of Dy can be markedly reduced. As for manufacturer of NdFeB magnet, we are also trying to optimize our process to reduce to dependence of HREE such as Dy and Tb. HS process have been introduced to solve the problem. With more and more people focusing and engaging on the REE industry, the price of REE will be more transparent without too many fluctuations. China is considering the problems of balancing the environment, energy sources, and labor sources. The application field about NdFeB such as wind turbine generator, HEV/EV, FA /OA is flourishing.

  4. Discovering objects in a blood recipient information system.

    PubMed

    Qiu, D; Junghans, G; Marquardt, K; Kroll, H; Mueller-Eckhardt, C; Dudeck, J

    1995-01-01

    Application of object-oriented (OO) methodologies has been generally considered as a solution to the problem of improving the software development process and managing the so-called software crisis. Among them, object-oriented analysis (OOA) is the most essential and is a vital prerequisite for the successful use of other OO methodologies. Though there are already a good deal of OOA methods published, the most important aspect common to all these methods: discovering objects classes truly relevant to the given problem domain, has remained a subject to be intensively researched. In this paper, using the successful development of a blood recipient information system as an example, we present our approach which is based on the conceptual framework of responsibility-driven OOA. In the discussion, we also suggest that it may be inadequate to simply attribute the software crisis to the waterfall model of the software development life-cycle. We are convinced that the real causes for the failure of some software and information systems should be sought in the methodologies used in some crucial phases of the software development process. Furthermore, a software system can also fail if object classes essential to the problem domain are not discovered, implemented and visualized, so that the real-world situation cannot be faithfully traced by it.

  5. Discovering Your Radiant Self: A Transpersonal Approach to Expressing Your Potential.

    ERIC Educational Resources Information Center

    Klimek, Paula; Canfield, Jack

    1979-01-01

    Presents a process combining a drawing experience with exercises learned in psychosynthesis training to help people discover what transpersonal qualities are attempting to manifest themselves through their personalities. (Author/BEF)

  6. NASA's Kepler Mission Discovers First Earth-size Planet in Habitable Zone of Another Star (Reporter Package)

    NASA Image and Video Library

    2014-04-17

    NASA's Kepler mission has discovered the first Earth-size planet orbiting in the habitable zone of a star outside our solar system. The newly discovered planet is called Kepler-186f and is about 10 percent larger than Earth.

  7. NI-DiscoverHistory: Meta-narrative for Explanation Bounding

    DTIC Science & Technology

    2014-01-01

    this research during the summer of 2014. 4 References [1] D. Herman, Storytelling and the Sciences of Mind. MIT Press, 2013. [2] M. Mateas and P...ASM Project NI-DiscoverHistory: Meta-narrative for Explanation Bounding Tory S. Anderson1, Swaroop Vattam2, and David Aha3 1Grad Student Researcher ...Georgia Institute of Technology; torys.anderson@gatech.edu 2NRC postdoctoral Researcher ; Navy Center for Applied Research in AI; Naval Research

  8. Discovering Theorems in Abstract Algebra Using the Software "GAP"

    ERIC Educational Resources Information Center

    Blyth, Russell D.; Rainbolt, Julianne G.

    2010-01-01

    A traditional abstract algebra course typically consists of the professor stating and then proving a sequence of theorems. As an alternative to this classical structure, the students could be expected to discover some of the theorems even before they are motivated by classroom examples. This can be done by using a software system to explore a…

  9. Mineral resource of the month: rare earths

    USGS Publications Warehouse

    Hedrick, James B.

    2004-01-01

    As if classified as a top-secret project, the rare earths have been shrouded in secrecy. The principal ore mineral of the group, bastnäsite, rarely appears in the leading mineralogy texts. The long names of the rare-earth elements and some unusual arrangements of letters, many Scandinavian in origin, may have intimidated even those skilled in phonics. Somewhat obscurely labeled, the rare earths are neither rare nor earths (the historical term for oxides). They are a relatively abundant group of metallic elements that occur in nature as nonmetallic compounds and have hundreds of commercial applications.

  10. Discovering Network Structure Beyond Communities

    NASA Astrophysics Data System (ADS)

    Nishikawa, Takashi; Motter, Adilson E.

    2011-11-01

    To understand the formation, evolution, and function of complex systems, it is crucial to understand the internal organization of their interaction networks. Partly due to the impossibility of visualizing large complex networks, resolving network structure remains a challenging problem. Here we overcome this difficulty by combining the visual pattern recognition ability of humans with the high processing speed of computers to develop an exploratory method for discovering groups of nodes characterized by common network properties, including but not limited to communities of densely connected nodes. Without any prior information about the nature of the groups, the method simultaneously identifies the number of groups, the group assignment, and the properties that define these groups. The results of applying our method to real networks suggest the possibility that most group structures lurk undiscovered in the fast-growing inventory of social, biological, and technological networks of scientific interest.

  11. Community Assembly Processes of the Microbial Rare Biosphere.

    PubMed

    Jia, Xiu; Dini-Andreote, Francisco; Falcão Salles, Joana

    2018-03-14

    Our planet teems with microorganisms that often present a skewed abundance distribution in a local community, with relatively few dominant species coexisting alongside a high number of rare species. Recent studies have demonstrated that these rare taxa serve as limitless reservoirs of genetic diversity, and perform disproportionate types of functions despite their low abundances. However, relatively little is known about the mechanisms controlling rarity and the processes promoting the development of the rare biosphere. Here, we propose the use of multivariate cut-offs to estimate rare species and phylogenetic null models applied to predefined rare taxa to disentangle the relative influences of ecoevolutionary processes mediating the assembly of the rare biosphere. Importantly, the identification of the factors controlling rare species assemblages is critical for understanding the types of rarity, how the rare biosphere is established, and how rare microorganisms fluctuate over spatiotemporal scales, thus enabling prospective predictions of ecosystem responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Accumulation of rare earth elements by siderophore-forming Arthrobacter luteolus isolated from rare earth environment of Chavara, India.

    PubMed

    Emmanuel, E S Challaraj; Ananthi, T; Anandkumar, B; Maruthamuthu, S

    2012-03-01

    In this study, Arthrobacter luteolus, isolated from rare earth environment of Chavara (Quilon district, Kerala, India), were found to produce catechol-type siderophores. The bacterial strain accumulated rare earth elements such as samarium and scandium. The siderophores may play a role in the accumulation of rare earth elements. Catecholate siderophore and low-molecular-weight organic acids were found to be present in experiments with Arthrobacter luteolus. The influence of siderophore on the accumulation of rare earth elements by bacteria has been extensively discussed.

  13. OT discovered by MASTER during Fermi Trigger Num 430645968 follow up observations follow up observations

    NASA Astrophysics Data System (ADS)

    Tiurina, N.; Balanutsa, P.; Denisenko, D.; Lipunov, V.; Gorbovskoy, E.; Kornilov, V.; Chazov, V.; Kuznetsov, A.; Vladimirov, V.; Yecheistov, V.; Shumkov, V.; Ivanov, K.; Yazev, S.; Budnev, N.; Konstantinov, E.; Chuvalaev, O.; Poleshchuk, V.; Gress, O.; Parkhomenko, A.; Tlatov, A.; Dormidontov, D.; Senik, V.; Yurkov, V.; Sergienko, Y.; Varda, D.; Sinyakov, E.; Gabovich, A.; Krushinsky, V.; Zalozhnih, I.; Popov, A.; Bourdanov, A.; Podvorotny, P.; Shurpakov, S.; Levato, H.; Saffe, C.; Mallamaci, C.; Lopez, C.; Podest, F.

    2014-08-01

    MASTER-Tunka auto-detection system during follow-up Fermi Trigger 430645968 observations (GCN 16745) discovered OT source at: MASTER-Tunka auto-detection system discovered MASTER OT J230448.20+324534.1 at (RA, Dec) = 23h 04m 48.20s +32d 45m 34.1s on 2014-08-25.62245 UT.

  14. Let Students Discover an Important Physical Property of a Slinky

    ERIC Educational Resources Information Center

    Gash, Philip

    2016-01-01

    This paper describes a simple experiment that lets first-year physics and engineering students discover an important physical property of a Slinky. The restoring force for the fundamental oscillation frequency is provided only by those coils between the support and the Slinky center of mass.

  15. Rare earths, the lanthanides, yttrium and scandium

    USGS Publications Warehouse

    Hedrick, J.B.

    2006-01-01

    In 2005, rare earths were not mined in the United States. The major supplier, Molycorp, continued to maintain a large stockpile of rare-earth concentrates and compounds. Consumption decreased of refined rare-earth products. The United States remained a major importer and exporter of rare earths in 2005. During the same period, yttrium was not mined or refined in the US. Hence, supply of yttrium compounds for refined yttrium products came from China, France and Japan. Scandium was not also mined. World production was primarily in China, Russia and Ukraine. Demand for rare earths in 2006 is expected to be closely tied to economic conditions in the US.

  16. Rare Earth Metals: Resourcefulness and Recovery

    NASA Astrophysics Data System (ADS)

    Wang, Shijie

    2013-10-01

    When we appreciate the digital revolution carried over from the twentieth century with mobile communication and the Internet, and when we enjoy our high-tech lifestyle filled with iDevices, hybrid cars, wind turbines, and solar cells in this new century, we should also appreciate that all of these advanced products depend on rare earth metals to function. Although there are only 136,000 tons of annual worldwide demand, (Cho, Rare Earth Metals, Will We Have Enough?)1 rare earth metals are becoming such hot commodities on international markets, due to not only to their increasing uses, including in most critical military hardware, but also to Chinese growth, which accounts for 95% of global rare earth metal production. Hence, the 2013 technical calendar topic, planned by the TMS/Hydrometallurgy and Electrometallurgy Committee, is particularly relevant, with four articles (including this commentary) contributed to the JOM October Issue discussing rare earth metals' resourcefulness and recovery.

  17. Enzymatic approaches to rare sugar production.

    PubMed

    Zhang, Wenli; Zhang, Tao; Jiang, Bo; Mu, Wanmeng

    Rare sugars have recently attracted much attention because of their potential applications in the food, nutraceutical, and pharmaceutical industries. A systematic strategy for enzymatic production of rare sugars, named Izumoring, was developed >10years ago. The strategy consists of aldose-ketose isomerization, ketose C-3 epimerization, and monosaccharide oxidation-reduction. Recent development of the Izumoring strategy is reviewed herein, especially the genetic approaches to the improvement of rare sugar-producing enzymes and the applications of target-oriented bioconversion. In addition, novel non-Izumoring enzymatic approaches are also summarized, including enzymatic condensation, phosphorylation-dephosphorylation cascade reaction, aldose epimerization, ulosonic acid decarboxylation, and biosynthesis of rare disaccharides. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Rare earth metal-containing ionic liquids

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

    Prodius, Denis; Mudring, Anja-Verena

    As an innovative tool, ionic liquids (ILs) are widely employed as an alternative, smart, reaction media (vs. traditional solvents) offering interesting technology solutions for dissolving, processing and recycling of metal-containing materials. The costly mining and refining of rare earths (RE), combined with increasing demand for high-tech and energy-related applications around the world, urgently requires effective approaches to improve the efficiency of rare earth separation and recovery. In this context, ionic liquids appear as an attractive technology solution. Finally, this paper addresses the structural and coordination chemistry of ionic liquids comprising rare earth metals with the aim to add to understandingmore » prospects of ionic liquids in the chemistry of rare earths.« less

  19. Rare earth metal-containing ionic liquids

    DOE PAGES

    Prodius, Denis; Mudring, Anja-Verena

    2018-03-07

    As an innovative tool, ionic liquids (ILs) are widely employed as an alternative, smart, reaction media (vs. traditional solvents) offering interesting technology solutions for dissolving, processing and recycling of metal-containing materials. The costly mining and refining of rare earths (RE), combined with increasing demand for high-tech and energy-related applications around the world, urgently requires effective approaches to improve the efficiency of rare earth separation and recovery. In this context, ionic liquids appear as an attractive technology solution. Finally, this paper addresses the structural and coordination chemistry of ionic liquids comprising rare earth metals with the aim to add to understandingmore » prospects of ionic liquids in the chemistry of rare earths.« less

  20. Uptake and effect of rare earth elements on gene expression in Methylosinus trichosporium OB3b

    DOE PAGES

    Gu, Wenyu; Farhan Ul Haque, Muhammad; DiSpirito, Alan A.; ...

    2016-05-12

    It is well-known that M. trichosporium OB3b has two forms of methane monooxygenase responsible for the initial conversion of methane to methanol, a cytoplasmic (soluble) methane monooxygenase (sMMO) and a membrane-associated (particulate) methane monooxygenase (pMMO) and that copper strongly regulates expression of these alternative forms of MMO. More recently, it has been discovered that M. trichosporium OB3b has multiple types of the methanol dehydrogenase (MeDH), i.e. the Mxa-MeDH and Xox-MeDH, and the expression of these two forms is regulated by the availability of the rare earth element, cerium. Here we extend these studies and show that lanthanum, praseodymium, neodymium andmore » samarium also regulate expression of alternative forms of MeDH. The effect of these rare earth elements on MeDH expression, however, was only observed in the absence of copper. Further, a mutant of M. trichosporium OB3b where the Mxa-MeDH was knocked out was able to grow in the presence of lanthanum, praseodymium and neodymium, but was not able to grow in the presence of samarium. In conclusion, collectively these data suggest that multiple levels of gene regulation by metals exist in M. trichosporium OB3b but that copper overrides the effect of other metals by an as yet unknown mechanism.« less

  1. Rare Earth Polyoxometalates.

    PubMed

    Boskovic, Colette

    2017-09-19

    Longstanding and important applications make use of the chemical and physical properties of both rare earth metals and polyoxometalates of early transition metals. The catalytic, optical, and magnetic features of rare earth metal ions are well-known, as are the reversible multielectron redox and photoredox capabilities of polyoxomolybdates and polyoxotungstates. The combination of rare earth ions and polyoxometalates in discrete molecules and coordination polymers is of interest for the unique combination of chemical and physical properties that can arise. This Account surveys our efforts to synthesize and investigate compounds with rare earth ions and polyoxometalates (RE-POMs), sometimes with carboxylate-based organic coligands. Our general synthetic approach is "bottom-up", which affords well-defined nanoscale molecules, typically in crystalline form and amenable to single-crystal X-ray diffraction for structure determination. Our particular focus is on elucidation of the physical properties conferred by the different structural components with a view to ultimately being able to tune these properties chemically. For this purpose, we employ a variety of spectroscopic, magnetochemical, electrochemical, and scattering techniques in concert with theoretical modeling and computation. Studies of RE-POM single-molecule magnets (SMMs) have utilized magnetic susceptibility, inelastic neutron scattering, and ab initio calculations. These investigations have allowed characterization of the crystal field splitting of the rare earth(III) ions that is responsible for the SMM properties of slow magnetic relaxation and magnetization quantum tunneling. Such SMMs are promising for applications in quantum computing and molecular spintronics. Photophysical measurements of a family of hybrid RE-POMs with organic ligands have afforded insights into sensitization of Tb(III) and Eu(III) emission through both organic and polyoxometalate chromophores in the same molecule. Detailed

  2. Line drawing of anomaly discovered in redesigned shuttle motor nozzle

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Line drawing titled 'DM-9 Case-to-Nozzle Joint' shows anomaly discovered in redesigned shuttle motor nozzle. The second full-duration test firing of NASA's redesigned Space Shuttle solid rocket motor (SRM), designated DM-9, was conducted 12-23-87 at Morton Thiokol's Wasatch facility in Utah. A post-test examination of the motor has revealed an anomaly in one nozzle component. Material was discovered missing from the nozzle outer boot ring, a large carbon phenolic composite ring used to anchor one end of the flexible boot that allows the nozzle to move and 'steer' the vehicle. About one-third of the missing 160 degrees of missing ring material was found adjacent to the forward nozzle section inside the motor. This diagram shows the location of the nozzle joint on an assembled SRM, and points out the shaded location of the outer boot ring that circles the motor within the nozzle joint.

  3. Ternary rare earth-lanthanide sulfides

    DOEpatents

    Takeshita, Takuo; Gschneidner JR., Karl A.; Beaudry, Bernard J.

    1987-01-06

    A new ternary rare earth sulfur compound having the formula: where M is a rare earth element selected from the group europium, samarium and ytterbium and x=0.15 to 0.8. The compound has good high-temperature thermoelectric properties and exhibits long-term structural stability up to 1000.degree. C.

  4. [RARE DISEASES DTC: DIAGNOSIS, TREATMENT AND CARE].

    PubMed

    Mendlovic, Joseph; Barash, Hila; Yardeni, Hadar; Banet-Levi, Yonit; Yonath, Hagith; Raas-Rothschild, Annick

    2016-04-01

    Rare diseases are chronic, progressive genetic disorders, which affect around 6-8% of the general population, mainly children. Therefore, in Israel approximately 500,000 people are probably affected by a rare disease. In this article, we review some of the issues pertaining to rare diseases, such as the need for accurate diagnosis which is necessary not only for specific care and treatment but also for informed family planning. In addition, we review the impact of the activities of patients' organizations on the awareness of rare diseases and their involvement in the creation of the Orphan Drug Act, which was the leading point on the way to drug development worldwide. During the last few years networks for reaching leading specialists' opinions on the way to proper diagnosis were created. Thereafter, the next generation genetic technologies, such as exome sequencing, have been a revolution in terms of options and hope for patients with rare undiagnosed diseases. Patients with rare diseases and their families are a challenge to the health care system, not only in terms of diagnosis and therapy, but also in terms of special needs. In addition, deciphering molecular pathways of rare diseases might be the key for understanding molecular events involved in common disorders. We emphasize the duty to ensure appropriate capacity and equal access to follow-up and clinical management of patients with rare diseases in Israel.

  5. Identification of a rare BMP pathway mutation in a non-syndromic human brain arteriovenous malformation via exome sequencing.

    PubMed

    Walcott, Brian P; Winkler, Ethan A; Zhou, Sirui; Birk, Harjus; Guo, Diana; Koch, Matthew J; Stapleton, Christopher J; Spiegelman, Dan; Dionne-Laporte, Alexandre; Dion, Patrick A; Kahle, Kristopher T; Rouleau, Guy A; Lawton, Michael T

    2018-01-01

    Brain arteriovenous malformations (AVMs) are abnormal connections between arteries and veins that can result in hemorrhagic stroke. A genetic basis for AVMs is suspected, and we investigated potential mutations in a 14-year-old girl who developed a recurrent brain AVM. Whole-exome sequencing (WES) of AVM lesion tissue and blood was performed accompanied by in silico modeling, protein expression observation in lesion tissue and zebrafish modeling. A stop-gain mutation (c.C739T:p.R247X) in the gene SMAD family member 9 ( SMAD9 ) was discovered. In the human brain tissue, immunofluorescent staining demonstrated a vascular predominance of SMAD9 at the protein level. Vascular SMAD9 was markedly reduced in AVM peri-nidal blood vessels, which was accompanied by a decrease in phosphorylated SMAD4, a downstream effector protein of the bone morphogenic protein signaling pathway. Zebrafish modeling ( Tg kdrl:eGFP ) of the morpholino splice site and translation-blocking knockdown of SMAD9 resulted in abnormal cerebral artery-to-vein connections with morphologic similarities to human AVMs. Orthogonal trajectories of evidence established a relationship between the candidate mutation discovered in SMAD9 via WES and the clinical phenotype. Replication in similar rare cases of recurrent AVM, or even more broadly sporadic AVM, may be informative in building a more comprehensive understanding of AVM pathogenesis.

  6. Taxonomy of rare genetic metabolic bone disorders.

    PubMed

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

    2015-10-01

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

  7. Discover 4-H Clubs: The Essential Resource for 4-H

    ERIC Educational Resources Information Center

    MacArthur, Stacey; Nelson, Cindy; Brower, Naomi; Memmott, Margie; Peterson, Gaelynn

    2016-01-01

    Obstacles facing new 4-H volunteers include time constraints and difficulty finding project-specific information, resources, and opportunities available for club members. As a solution to these obstacles and an aid for assisting volunteers in becoming confident in delivering information to youth, content experts produced Discover 4-H Clubs, a…

  8. Simultaneously Discovering and Localizing Common Objects in Wild Images.

    PubMed

    Wang, Zhenzhen; Yuan, Junsong

    2018-09-01

    Motivated by the recent success of supervised and weakly supervised common object discovery, in this paper, we move forward one step further to tackle common object discovery in a fully unsupervised way. Generally, object co-localization aims at simultaneously localizing objects of the same class across a group of images. Traditional object localization/detection usually trains specific object detectors which require bounding box annotations of object instances, or at least image-level labels to indicate the presence/absence of objects in an image. Given a collection of images without any annotations, our proposed fully unsupervised method is to simultaneously discover images that contain common objects and also localize common objects in corresponding images. Without requiring to know the total number of common objects, we formulate this unsupervised object discovery as a sub-graph mining problem from a weighted graph of object proposals, where nodes correspond to object proposals, and edges represent the similarities between neighbouring proposals. The positive images and common objects are jointly discovered by finding sub-graphs of strongly connected nodes, with each sub-graph capturing one object pattern. The optimization problem can be efficiently solved by our proposed maximal-flow-based algorithm. Instead of assuming that each image contains only one common object, our proposed solution can better address wild images where each image may contain multiple common objects or even no common object. Moreover, our proposed method can be easily tailored to the task of image retrieval in which the nodes correspond to the similarity between query and reference images. Extensive experiments on PASCAL VOC 2007 and Object Discovery data sets demonstrate that even without any supervision, our approach can discover/localize common objects of various classes in the presence of scale, view point, appearance variation, and partial occlusions. We also conduct broad

  9. Rare Disease Roadmap: Navigating the challenges and barriers to deliver improved outcomes for patients living with a Rare Disease

    USDA-ARS?s Scientific Manuscript database

    Rare Disease registries have now been recognized as a global priority for progress in monitoring, documenting natural course, preventing and treating rare diseases. However, a disease registry is only one element of Rare Disease translational research. Here, we outline what we believe are ten key co...

  10. Patterns of rare and abundant marine microbial eukaryotes.

    PubMed

    Logares, Ramiro; Audic, Stéphane; Bass, David; Bittner, Lucie; Boutte, Christophe; Christen, Richard; Claverie, Jean-Michel; Decelle, Johan; Dolan, John R; Dunthorn, Micah; Edvardsen, Bente; Gobet, Angélique; Kooistra, Wiebe H C F; Mahé, Frédéric; Not, Fabrice; Ogata, Hiroyuki; Pawlowski, Jan; Pernice, Massimo C; Romac, Sarah; Shalchian-Tabrizi, Kamran; Simon, Nathalie; Stoeck, Thorsten; Santini, Sébastien; Siano, Raffaele; Wincker, Patrick; Zingone, Adriana; Richards, Thomas A; de Vargas, Colomban; Massana, Ramon

    2014-04-14

    Biological communities are normally composed of a few abundant and many rare species. This pattern is particularly prominent in microbial communities, in which most constituent taxa are usually extremely rare. Although abundant and rare subcommunities may present intrinsic characteristics that could be crucial for understanding community dynamics and ecosystem functioning, microbiologists normally do not differentiate between them. Here, we investigate abundant and rare subcommunities of marine microbial eukaryotes, a crucial group of organisms that remains among the least-explored biodiversity components of the biosphere. We surveyed surface waters of six separate coastal locations in Europe, independently considering the picoplankton, nanoplankton, and microplankton/mesoplankton organismal size fractions. Deep Illumina sequencing of the 18S rRNA indicated that the abundant regional community was mostly structured by organismal size fraction, whereas the rare regional community was mainly structured by geographic origin. However, some abundant and rare taxa presented similar biogeography, pointing to spatiotemporal structure in the rare microeukaryote biosphere. Abundant and rare subcommunities presented regular proportions across samples, indicating similar species-abundance distributions despite taxonomic compositional variation. Several taxa were abundant in one location and rare in other locations, suggesting large oscillations in abundance. The substantial amount of metabolically active lineages found in the rare biosphere suggests that this subcommunity constitutes a diversity reservoir that can respond rapidly to environmental change. We propose that marine planktonic microeukaryote assemblages incorporate dynamic and metabolically active abundant and rare subcommunities, with contrasting structuring patterns but fairly regular proportions, across space and time. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A New Population of High-z, Dusty Lyman-alpha Emitters and Blobs Discovered by WISE: Feedback Caught in the Act?

    NASA Technical Reports Server (NTRS)

    Bridge, Carrie R.; Blain, Andrew; Borys, Colin J. K.; Petty, Sara; Benford, Dominic; Eisenhardt, Peter; Farrah, Duncan; Griffith, Roger, L.; Jarrett, Tom; Lonsdale, Carol; hide

    2013-01-01

    By combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W. M. Keck telescope, we discover a mid-IR color criterion that yields a 78% success rate in identifying rare, typically radio-quiet, 1.6 approx. < z approx. < 4.6 dusty Ly-alpha emitters (LAEs). Of these, at least 37% have emission extended on scales of 30-100 kpc and are considered Ly-alpha "blobs" (LABs). The objects have a surface density of only approx.. 0.1 deg(exp -2), making them rare enough that they have been largely missed in deep, small area surveys. We measured spectroscopic redshifts for 92 of these galaxies, and find that the LAEs (LABs) have a median redshift of 2.3 (2.5). The WISE photometry coupled with data from Herschel (Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA) reveals that these galaxies are in the Hyper Luminous IR galaxy regime (L(sub IR) approx. > 10(exp 13)-10(exp 14) Solar L) and have warm colors. They are typically more luminous and warmer than other dusty, z approx.. 2 populations such as submillimeter-selected galaxies and dust-obscured galaxies. These traits are commonly associated with the dust being illuminated by intense active galactic nucleus activity. We hypothesize that the combination of spatially extended Ly-alpha, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing brief, intense "feedback" transforming them from an extreme dusty starburst/QSO into a mature galaxy.

  12. Replacing the Rare Earth Intellectual Capital

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

    Gschneidner, Jr., Karl

    2011-04-01

    The rare earth crisis slowly evolved during a 10 to 15 year period beginning in the mid-1980s, when the Chinese began to export mixed rare earth concentrates. In the early 1990s, they started to move up the supply chain and began to export the individual rare earth oxides and metals. By the late 1990s the Chinese exported higher value products, such as magnets, phosphors, polishing compounds, catalysts; and in the 21st century they supplied finished products including electric motors, computers, batteries, liquid-crystal displays (LCDs), TVs and monitors, mobile phones, iPods and compact fluorescent lamp (CFL) light bulbs. As they movedmore » to higher value products, the Chinese slowly drove the various industrial producers and commercial enterprises in the US, Europe and Japan out of business by manipulating the rare earth commodity prices. Because of this, the technically trained rare earth engineers and scientists who worked in areas from mining to separations, to processing to production, to manufacturing of semifinished and final products, were laid-off and moved to other fields or they retired. However, in the past year the Chinese have changed their philosophy of the 1970s and 1980s of forming a rare earth cartel to control the rare earth markets to one in which they will no longer supply the rest of the world (ROW) with their precious rare earths, but instead will use them internally to meet the growing demand as the Chinese standard of living increases. To this end, they have implemented and occasionally increased export restrictions and added an export tariff on many of the high demand rare earth elements. Now the ROW is quickly trying to start up rare earth mines, e.g. Molycorp Minerals in the US and Lynas Corp. in Australia, to cover this shortfall in the worldwide market, but it will take about five years for the supply to meet the demand, even as other mines in the ROW become productive. Unfortunately, today there is a serious lack of technically

  13. Enhanced pinning in mixed rare earth-123 films

    DOEpatents

    Driscoll, Judith L [Los Alamos, NM; Foltyn, Stephen R [Los Alamos, NM

    2009-06-16

    An superconductive article and method of forming such an article is disclosed, the article including a substrate and a layer of a rare earth barium cuprate film upon the substrate, the rare earth barium cuprate film including two or more rare earth metals capable of yielding a superconductive composition where ion size variance between the two or more rare earth metals is characterized as greater than zero and less than about 10.times.10.sup.-4, and the rare earth barium cuprate film including two or more rare earth metals is further characterized as having an enhanced critical current density in comparison to a standard YBa.sub.2Cu.sub.3O.sub.y composition under identical testing conditions.

  14. A Genome-Wide Linkage Study for Chronic Obstructive Pulmonary Disease in a Dutch Genetic Isolate Identifies Novel Rare Candidate Variants.

    PubMed

    Nedeljkovic, Ivana; Terzikhan, Natalie; Vonk, Judith M; van der Plaat, Diana A; Lahousse, Lies; van Diemen, Cleo C; Hobbs, Brian D; Qiao, Dandi; Cho, Michael H; Brusselle, Guy G; Postma, Dirkje S; Boezen, H M; van Duijn, Cornelia M; Amin, Najaf

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is a complex and heritable disease, associated with multiple genetic variants. Specific familial types of COPD may be explained by rare variants, which have not been widely studied. We aimed to discover rare genetic variants underlying COPD through a genome-wide linkage scan. Affected-only analysis was performed using the 6K Illumina Linkage IV Panel in 142 cases clustered in 27 families from a genetic isolate, the Erasmus Rucphen Family (ERF) study. Potential causal variants were identified by searching for shared rare variants in the exome-sequence data of the affected members of the families contributing most to the linkage peak. The identified rare variants were then tested for association with COPD in a large meta-analysis of several cohorts. Significant evidence for linkage was observed on chromosomes 15q14-15q25 [logarithm of the odds (LOD) score = 5.52], 11p15.4-11q14.1 (LOD = 3.71) and 5q14.3-5q33.2 (LOD = 3.49). In the chromosome 15 peak, that harbors the known COPD locus for nicotinic receptors, and in the chromosome 5 peak we could not identify shared variants. In the chromosome 11 locus, we identified four rare (minor allele frequency (MAF) <0.02), predicted pathogenic, missense variants. These were shared among the affected family members. The identified variants localize to genes including neuroblast differentiation-associated protein ( AHNAK ), previously associated with blood biomarkers in COPD, phospholipase C Beta 3 ( PLCB3 ), shown to increase airway hyper-responsiveness, solute carrier family 22-A11 ( SLC22A11 ), involved in amino acid metabolism and ion transport, and metallothionein-like protein 5 ( MTL5 ), involved in nicotinate and nicotinamide metabolism. Association of SLC22A11 and MTL5 variants were confirmed in the meta-analysis of 9,888 cases and 27,060 controls. In conclusion, we have identified novel rare variants in plausible genes related to COPD. Further studies utilizing large sample

  15. Rare Disease Terminology and Definitions-A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group.

    PubMed

    Richter, Trevor; Nestler-Parr, Sandra; Babela, Robert; Khan, Zeba M; Tesoro, Theresa; Molsen, Elizabeth; Hughes, Dyfrig A

    2015-09-01

    At present, there is no universal definition of rare disease. To provide an overview of rare disease definitions currently used globally. We systematically searched for definitions related to rare disease from organizations in 32 international jurisdictions. Descriptive statistics of definitions were generated and prevalence thresholds were calculated. We identified 296 definitions from 1109 organizations. The terms "rare disease(s)" and "orphan drug(s)" were used most frequently (38% and 27% of the definitions, respectively). Qualitative descriptors such as "life-threatening" were used infrequently. A prevalence threshold was specified in at least one definition in 88% of the jurisdictions. The average prevalence threshold across organizations within individual jurisdictions ranged from 5 to 76 cases/100,000 people. Most jurisdictions (66%) had an average prevalence threshold between 40 and 50 cases/100,000 people, with a global average of 40 cases/100,000 people. Prevalence thresholds used by different organizations within individual jurisdictions varied substantially. Across jurisdictions, umbrella patient organizations had the highest (most liberal) average prevalence threshold (47 cases/100,000 people), whereas private payers had the lowest threshold (18 cases/100,000 people). Despite variation in the terminology and prevalence thresholds used to define rare diseases among different jurisdictions and organizations, the terms "rare disease" and "orphan drug" are used most widely and the average prevalence threshold is between 40 and 50 cases/100,000 people. These findings highlight the existing diversity among definitions of rare diseases, but suggest that any attempts to harmonize rare disease definitions should focus on standardizing objective criteria such as prevalence thresholds and avoid qualitative descriptors. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  16. Rare earths

    USGS Publications Warehouse

    Gambogi, J.

    2013-01-01

    Global mine production of rare earths was estimated to have declined slightly in 2012 relative to 2011 (Fig. 1). Production in China was estimated to have decreased to 95 from 105 kt (104,700 from 115,700 st) in 2011, while new mine production in the United States and Australia increased.

  17. Fortuitously discovered liver lesions.

    PubMed

    Dietrich, Christoph F; Sharma, Malay; Gibson, Robert N; Schreiber-Dietrich, Dagmar; Jenssen, Christian

    2013-06-07

    The fortuitously discovered liver lesion is a common problem. Consensus might be expected in terms of its work-up, and yet there is none. This stems in part from the fact that there is no preventive campaign involving the early detection of liver tumors other than for patients with known liver cirrhosis and oncological patients. The work-up (detection and differential diagnosis) of liver tumors comprises theoretical considerations, history, physical examination, laboratory tests, standard ultrasound, Doppler ultrasound techniques, contrast-enhanced ultrasound (CEUS), computed tomography and magnetic resonance imaging, as well as image-guided biopsy. CEUS techniques have proved to be the most pertinent method; these techniques became part of the clinical routine about 10 years ago in Europe and Asia and are used for a variety of indications in daily clinical practice. CEUS is in many cases the first and also decisive technical intervention for detecting and characterizing liver tumors. This development is reflected in many CEUS guidelines, e.g., in the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 as well as the recently published World Federation for Ultrasound in Medicine and Biology-EFSUMB guidelines 2012. This article sets out considerations for making a structured work-up of incidental liver tumors feasible.

  18. Possibility as monosaccharide laxative of rare sugar alcohols.

    PubMed

    Oosaka, Kazumasa

    2009-05-01

    Allitol, D-talitol and L-iditol are sugar alcohols that are rare in nature. Due to their previous rarity, little is known about the laxative effects of these rare sugar alcohols. Therefore, reliable data on the laxative effect that these sugar alcohols cause in experimental animals could help to evaluate the effectiveness of new monosaccharide laxative drugs. To investigate the laxative effect of rare sugar alcohols, the study was designed to observe the diarrhea that occurred after oral administration of these sugar alcohols in mice. Moreover, to investigate the influence on intestinal function of rare sugar alcohols, the study was designed to examine small intestine transit and the luminal water content. Results indicated that rare sugar alcohols have a laxative effect in mice. Diarrhea started at a dose of 4.95 g/kg of rare sugar alcohols. There was a statistically significant laxative effect for D-talitol and L-iditol at a dose of 9.9 g/kg as compared to vehicle. Moreover, rare sugar alcohols significantly increased the small intestinal transit and the luminal water content of the small intestine and cecum in mice as compared to each vehicle. Overall, L-iditol greatly changes the function of intestine. In conclusion, rare sugar alcohols increase water content in small intestine and accelerate small intestine transit. These results support laxative effect of rare sugar alcohols. Therefore, rare sugar alcohols may be useful as monosaccharide laxatives and may be used to treat constipation.

  19. A Global Approach to Rare Diseases Research and Orphan Products Development: The International Rare Diseases Research Consortium (IRDiRC).

    PubMed

    Cutillo, Christine M; Austin, Christopher P; Groft, Stephen C

    2017-01-01

    Rare diseases present unique challenges to researchers due to the global distribution of patients, complexity and low prevalence of each disease, and limited availability of data. They are also overwhelming and costly for patients, their families, communities, and society. As such, global integration of rare diseases research is necessary to accelerate the understanding, diagnosis, and treatment of rare disorders. The International Rare Diseases Research Consortium (IRDiRC) was born out of that need for a coordinated international community. IRDiRC was launched in 2011 to facilitate cooperation and collaboration on a global scale among the many stakeholders active in rare diseases research to stimulate better coordination, and thereby maximize output of rare diseases research efforts around the world. Members include funders, academic researchers, companies, and patient advocacy organizations all of whom share the common goals and principles of IRDiRC. The overarching objectives of the Consortium are to contribute to the development of 200 new therapies and a means to diagnose most rare diseases, by 2020. As IRDiRC approaches the end of its fifth year, these initial objectives have been largely achieved and new partners from across the globe are joining. This presents the Consortium with the exciting opportunity to set new and even more ambitious goals for the next phase with the ultimate goal of improved health through faster and better diagnostic capabilities and novel therapies for people living with rare diseases and conditions throughout the world.

  20. Computer-assisted initial diagnosis of rare diseases

    PubMed Central

    Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert

    2016-01-01

    Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534

  1. NASA's Kepler Mission Discovers Multiple Planets Orbiting Twin Suns (Reporter Pkg)

    NASA Image and Video Library

    2012-08-28

    NASA's Kepler mission has discovered the first transiting circumbinary system -- multiple planets orbiting two suns -- 4,900 light-years from Earth, in the constellation Cygnus, proving that more than one planets can form and survive in orbit around a binary star.

  2. Rare Earth Garnet Selective Emitter

    NASA Technical Reports Server (NTRS)

    Lowe, Roland A.; Chubb, Donald L.; Farmer, Serene C.; Good, Brian S.

    1994-01-01

    Thin film Ho-YAG and Er-YAG emitters with a platinum substrate exhibit high spectral emittance in the emission band (epsilon(sub lambda) approx. = 0.75, sup 4)|(sub 15/2) - (sup 4)|(sub 13/2),for Er-YAG and epsilon(sub lambda) approx. = 0.65, (sup 5)|(sub 7) - (sup 5)|(sub 8) for Ho-YAG) at 1500 K. In addition, low out-of-band spectral emittance, epsilon(sub lambda) less than 0.2, suggest these materials would be excellent candidates for high efficiency selective emitters in thermophotovoltaic (TPV) systems operating at moderate temperatures (1200-1500 K). Spectral emittance measurements of the thin films were made (1.2 less than lambda less than 3.0 microns) and compared to the theoretical emittances calculated using measured values of the spectral extinction coefficient. In this paper we present the results for a new class of rare earth ion selective emitters. These emitters are thin sections (less than 1 mm) of yttrium aluminum garnet (YAG) single crystal with a rare earth substitutional impurity. Selective emitters in the near IR are of special interest for thermophotovoltaic (TPV) energy conversion. The most promising solid selective emitters for use in a TPV system are rare earth oxides. Early spectral emittance work on rare earth oxides showed strong emission bands in the infrared (0.9 - 3 microns). However, the emittance outside the emission band was also significant and the efficiency of these emitters was low. Recent improvements in efficiency have been made with emitters fabricated from fine (5 - 10 microns) rare earth oxide fibers similar to the Welsbach mantle used in gas lanterns. However, the rare earth garnet emitters are more rugged than the mantle type emitters. A thin film selective emitter on a low emissivity substrate such as gold, platinum etc., is rugged and easily adapted to a wide variety of thermal sources. The garnet structure and its many subgroups have been successfully used as hosts for rare earth ions, introduced as substitutional

  3. Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

    PubMed Central

    Bogaerts, Jan; Sydes, Matthew R.; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M.; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J.; Law, Kate; Trimble, Ted; Seymour, Matthew

    2015-01-01

    Background The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. Settings The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional – usually randomised – clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. Results The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Interpretation Trials can be designed using a wide array of possibilities. There is no ‘one size fits all’ solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. PMID:25542058

  4. Clinical trial designs for rare diseases: studies developed and discussed by the International Rare Cancers Initiative.

    PubMed

    Bogaerts, Jan; Sydes, Matthew R; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J; Law, Kate; Trimble, Ted; Seymour, Matthew

    2015-02-01

    The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Chandra Discovers Cosmic Cannonball

    NASA Astrophysics Data System (ADS)

    2007-11-01

    One of the fastest moving stars ever seen has been discovered with NASA's Chandra X-ray Observatory. This cosmic cannonball is challenging theories to explain its blistering speed. Astronomers used Chandra to observe a neutron star, known as RX J0822-4300, over a period of about five years. During that span, three Chandra observations clearly show the neutron star moving away from the center of the Puppis A supernova remnant. This remnant is the stellar debris field created during the same explosion in which the neutron star was created about 3700 years ago. Chandra X-ray Image of RX J0822-4300 in Puppis A Chandra X-ray Image of RX J0822-4300 in Puppis A By combining how far it has moved across the sky with its distance from Earth, astronomers determined the neutron star is moving at over 3 million miles per hour. At this rate, RX J0822-4300 is destined to escape from the Milky Way after millions of years, even though it has only traveled about 20 light years so far. "This star is moving at 3 million miles an hour, but it's so far away that the apparent motion we see in five years is less than the height of the numerals in the date on a penny, seen from the length of a football field," said Frank Winkler of Middlebury College in Vermont. "It's remarkable, and a real testament to the power of Chandra, that such a tiny motion can be measured." Labeled Image of RX J0822-4300 in Puppis A Labeled Image of RX J0822-4300 in Puppis A "Just after it was born, this neutron star got a one-way ticket out of the Galaxy," said co-author Robert Petre of NASA's Goddard Space Flight Center in Greenbelt, Md. "Astronomers have seen other stars being flung out of the Milky Way, but few as fast as this." So-called hypervelocity stars have been previously discovered shooting out of the Milky Way with speeds around one million miles per hour. One key difference between RX J0822-4300 and these other reported galactic escapees is the source of their speed. The hypervelocity stars are

  6. Ternary rare earth-lanthanide sulfides

    DOEpatents

    Takeshita, Takuo; Gschneidner, Jr., Karl A.; Beaudry, Bernard J.

    1987-01-06

    A new ternary rare earth sulfur compound having the formula: La.sub.3-x M.sub.x S.sub.4 where M is a rare earth element selected from the group europium, samarium and ytterbium and x=0.15 to 0.8. The compound has good high-temperature thermoelectric properties and exhibits long-term structural stability up to 1000.degree. C.

  7. Ainhum - A Rare Case Report.

    PubMed

    Prabhu, Ravi; Kannan, Narayanasamy Subbaraju; Vinoth, Sundaresan; Praveen, Chinnappan Balasubramanian

    2016-04-01

    The term 'AINHUM' is derived from the African word meaning 'to saw or cut'. True ainhum otherwise called dactylolysis spontanea is a condition involving soft tissue or digits with constricting rings commonly presenting in fifth toes, usually bilateral. It is to be differentiated from Pseudo-ainhum that occurs secondary to some hereditary and nonhereditary diseases that lead to annular constriction of digits. We report a rare case of true ainhum involving the left fourth toe only. It is a very rare case and a very few were reported worldwide. The highest incidence of ainhum has been reported in South Africa and South America. It is rarely reported in India. Ainhum when diagnosed and treated in early stages can be prevented from progressing to mutilating deformities.

  8. Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.

    PubMed

    Chen, Rui; Davis, Lea K; Guter, Stephen; Wei, Qiang; Jacob, Suma; Potter, Melissa H; Cox, Nancy J; Cook, Edwin H; Sutcliffe, James S; Li, Bingshan

    2017-01-01

    Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown. In this study, pursuing the hypothesis that de novo variants (DNVs) and rare risk alleles acting in a recessive mode may play an important role in predisposition of hyperserotonemia in people with ASD, we carried out whole exome sequencing (WES) in 116 ASD parent-proband trios with most (107) probands having 5-HT measurements. Combined with published ASD DNVs, we identified USP15 as having recurrent de novo loss of function mutations and discovered evidence supporting two other known genes with recurrent DNVs ( FOXP1 and KDM5B ). Genes harboring functional DNVs significantly overlap with functional/disease gene sets known to be involved in ASD etiology, including FMRP targets and synaptic formation and transcriptional regulation genes. We grouped the probands into High-5HT and Normal-5HT groups based on normalized serotonin levels, and used network-based gene set enrichment analysis (NGSEA) to identify novel hyperserotonemia-related ASD genes based on LoF and missense DNVs. We found enrichment in the High-5HT group for a gene network module (DAWN-1) previously implicated in ASD, and this points to the TGF-β pathway and cell junction processes. Through analysis of rare recessively acting variants (RAVs), we also found that rare compound heterozygotes (CHs) in the High-5HT group were enriched for loci in an ASD-associated gene set. Finally, we carried out rare variant group-wise transmission

  9. A Bayesian Method for Evaluating and Discovering Disease Loci Associations

    PubMed Central

    Jiang, Xia; Barmada, M. Michael; Cooper, Gregory F.; Becich, Michael J.

    2011-01-01

    Background A genome-wide association study (GWAS) typically involves examining representative SNPs in individuals from some population. A GWAS data set can concern a million SNPs and may soon concern billions. Researchers investigate the association of each SNP individually with a disease, and it is becoming increasingly commonplace to also analyze multi-SNP associations. Techniques for handling so many hypotheses include the Bonferroni correction and recently developed Bayesian methods. These methods can encounter problems. Most importantly, they are not applicable to a complex multi-locus hypothesis which has several competing hypotheses rather than only a null hypothesis. A method that computes the posterior probability of complex hypotheses is a pressing need. Methodology/Findings We introduce the Bayesian network posterior probability (BNPP) method which addresses the difficulties. The method represents the relationship between a disease and SNPs using a directed acyclic graph (DAG) model, and computes the likelihood of such models using a Bayesian network scoring criterion. The posterior probability of a hypothesis is computed based on the likelihoods of all competing hypotheses. The BNPP can not only be used to evaluate a hypothesis that has previously been discovered or suspected, but also to discover new disease loci associations. The results of experiments using simulated and real data sets are presented. Our results concerning simulated data sets indicate that the BNPP exhibits both better evaluation and discovery performance than does a p-value based method. For the real data sets, previous findings in the literature are confirmed and additional findings are found. Conclusions/Significance We conclude that the BNPP resolves a pressing problem by providing a way to compute the posterior probability of complex multi-locus hypotheses. A researcher can use the BNPP to determine the expected utility of investigating a hypothesis further. Furthermore, we

  10. What Is Going on Inside the Arrows? Discovering the Hidden Springs in Causal Models

    PubMed Central

    Murray-Watters, Alexander; Glymour, Clark

    2016-01-01

    Using Gebharter's (2014) representation, we consider aspects of the problem of discovering the structure of unmeasured sub-mechanisms when the variables in those sub-mechanisms have not been measured. Exploiting an early insight of Sober's (1998), we provide a correct algorithm for identifying latent, endogenous structure—sub-mechanisms—for a restricted class of structures. The algorithm can be merged with other methods for discovering causal relations among unmeasured variables, and feedback relations between measured variables and unobserved causes can sometimes be learned. PMID:27313331

  11. Discovering Communicable Scientific Knowledge from Spatio-Temporal Data

    NASA Technical Reports Server (NTRS)

    Schwabacher, Mark; Langley, Pat; Norvig, Peter (Technical Monitor)

    2001-01-01

    This paper describes how we used regression rules to improve upon a result previously published in the Earth science literature. In such a scientific application of machine learning, it is crucially important for the learned models to be understandable and communicable. We recount how we selected a learning algorithm to maximize communicability, and then describe two visualization techniques that we developed to aid in understanding the model by exploiting the spatial nature of the data. We also report how evaluating the learned models across time let us discover an error in the data.

  12. Discovering herbal functional groups of traditional Chinese medicine.

    PubMed

    He, Ping; Deng, Ke; Liu, Zhihai; Liu, Delin; Liu, Jun S; Geng, Zhi

    2012-03-30

    For the traditional Chinese medicine (TCM), a prescription for a patient often contains several herbs. Some herbs are often used together in prescriptions, and these herbs can be considered as a functional group. In this paper, we propose an approach for discovering herbal functional groups from a large set of prescriptions recorded in TCM books. These functional groups are allowed to overlap with each other. Our approach is validated with a simulation study and applied to a data set containing thousands of TCM prescriptions. Copyright © 2011 John Wiley & Sons, Ltd.

  13. Interactive Gaussian Graphical Models for Discovering Depth Trends in ChemCam Data

    NASA Astrophysics Data System (ADS)

    Oyen, D. A.; Komurlu, C.; Lanza, N. L.

    2018-04-01

    Interactive Gaussian graphical models discover surface compositional features on rocks in ChemCam targets. Our approach visualizes shot-to-shot relationships among LIBS observations, and identifies the wavelengths involved in the trend.

  14. Discovering weighted patterns in intron sequences using self-adaptive harmony search and back-propagation algorithms.

    PubMed

    Huang, Yin-Fu; Wang, Chia-Ming; Liou, Sing-Wu

    2013-01-01

    A hybrid self-adaptive harmony search and back-propagation mining system was proposed to discover weighted patterns in human intron sequences. By testing the weights under a lazy nearest neighbor classifier, the numerical results revealed the significance of these weighted patterns. Comparing these weighted patterns with the popular intron consensus model, it is clear that the discovered weighted patterns make originally the ambiguous 5SS and 3SS header patterns more specific and concrete.

  15. Discovering Sentinel Rules for Business Intelligence

    NASA Astrophysics Data System (ADS)

    Middelfart, Morten; Pedersen, Torben Bach

    This paper proposes the concept of sentinel rules for multi-dimensional data that warns users when measure data concerning the external environment changes. For instance, a surge in negative blogging about a company could trigger a sentinel rule warning that revenue will decrease within two months, so a new course of action can be taken. Hereby, we expand the window of opportunity for organizations and facilitate successful navigation even though the world behaves chaotically. Since sentinel rules are at the schema level as opposed to the data level, and operate on data changes as opposed to absolute data values, we are able to discover strong and useful sentinel rules that would otherwise be hidden when using sequential pattern mining or correlation techniques. We present a method for sentinel rule discovery and an implementation of this method that scales linearly on large data volumes.

  16. Rare cell isolation and analysis in microfluidics

    PubMed Central

    Chen, Yuchao; Li, Peng; Huang, Po-Hsun; Xie, Yuliang; Mai, John D.; Wang, Lin; Nguyen, Nam-Trung; Huang, Tony Jun

    2014-01-01

    Rare cells are low-abundance cells in a much larger population of background cells. Conventional benchtop techniques have limited capabilities to isolate and analyze rare cells because of their generally low selectivity and significant sample loss. Recent rapid advances in microfluidics have been providing robust solutions to the challenges in the isolation and analysis of rare cells. In addition to the apparent performance enhancements resulting in higher efficiencies and sensitivity levels, microfluidics provides other advanced features such as simpler handling of small sample volumes and multiplexing capabilities for high-throughput processing. All of these advantages make microfluidics an excellent platform to deal with the transport, isolation, and analysis of rare cells. Various cellular biomarkers, including physical properties, dielectric properties, as well as immunoaffinities, have been explored for isolating rare cells. In this Focus article, we discuss the design considerations of representative microfluidic devices for rare cell isolation and analysis. Examples from recently published works are discussed to highlight the advantages and limitations of the different techniques. Various applications of these techniques are then introduced. Finally, a perspective on the development trends and promising research directions in this field are proposed. PMID:24406985

  17. Mantle peridotite in newly discovered far-inland subduction complex, southwest Arizona: Initial report

    USGS Publications Warehouse

    Haxel, Gordon B.; Jacobson, Carl E.; Wittke, James H.

    2015-01-01

    The latest Cretaceous to early Palaeogene Orocopia Schist and related units are generally considered a low-angle subduction complex that underlies much of southern California and Arizona. A recently discovered exposure of Orocopia Schist at Cemetery Ridge west of Phoenix, Arizona, lies exceptionally far inland from the continental margin. Unexpectedly, this body of Orocopia Schist contains numerous blocks, as large as ~300 m, of variably serpentinized mantle peridotite. These are unique; elsewhere in the Orocopia and related schists, peridotite is rare and completely serpentinized. Peridotite and metaperidotite at Cemetery Ridge are of three principal types: (1) serpentinite and tremolite serpentinite, derived from dunite; (2) partially serpentinized harzburgite and olivine orthopyroxenite (collectively, harzburgite); and (3) granoblastic or schistose metasomatic rocks, derived from serpentinite, made largely of actinolite, calcic plagioclase, hercynite, and chlorite. In the serpentinite, paucity of relict olivine, relatively abundant magnetite (5%), and elevated Fe3+/Fe indicate advanced serpentinization. Harzburgite contains abundant orthopyroxene, only slightly serpentinized, and minor to moderate (1–15%) relict olivine. Mantle tectonite fabric is locally preserved. Several petrographic and geochemical characteristics of the peridotite at Cemetery Ridge are ambiguously similar to either abyssal or mantle-wedge (suprasubduction) peridotites and serpentinites. Least ambiguous are orthopyroxene compositions. Orthopyroxene is distinctively depleted in Al2O3, Cr2O3, and CaO, indicating mantle-wedge affinities. Initial interpretation of field and petrologic data suggests that the peridotite blocks in the Orocopia Schist subduction complex at Cemetery Ridge may be derived from the leading corner or edge of a mantle wedge, presumably in (pre-San Andreas fault) southwest California. However, derivation from a subducting plate is not precluded.

  18. Improved method for preparing rare earth sesquichalcogenides

    DOEpatents

    Takeshita, T.; Beaudry, B.J.; Gschneidner, K.A. Jr.

    1982-04-14

    An improved method for the preparation of high purity rare earth sesquichalcogenides is described. The rare earth, as one or more pieces of the metal, is sealed under a vacuum with a stoichiometric amount of sulfur or selenium and a small amount of iodine into a quartz reaction vessel. The sealed vessel is then heated to above the vaporization temperature of the chalcogen and below the melting temperature of the rare earth metal and maintained until the product has been formed. The iodine is then vaporized off leaving a pure product. The rare earth sulfides and selenides thus formed are useful as semiconductors and as thermoelectric generators. 3 tables.

  19. Alaska's rare earth deposits and resource potential

    USGS Publications Warehouse

    Barker, James C.; Van Gosen, Bradley S.

    2012-01-01

    Alaska’s known mineral endowment includes some of the largest and highest grade deposits of various metals, including gold, copper and zinc. Recently, Alaska has also been active in the worldwide search for sources of rare earth elements (REE) to replace exports now being limitedby China. Driven by limited supply of the rare earths, combined with their increasing use in new ‘green’ energy, lighting, transportation, and many other technological applications, the rare earth metals neodymium, europium and, in particular, the heavy rare earth elements terbium, dysprosium and yttrium are forecast to soon be in critical short supply (U.S. Department of Energy, 2010).

  20. Rare cancers: a sea of opportunity.

    PubMed

    Boyd, Niki; Dancey, Janet E; Gilks, C Blake; Huntsman, David G

    2016-02-01

    Rare cancers, as a collective, account for around a quarter of all cancer diagnoses and deaths. Historically, they have been divided into two groups: cancers defined by their unusual histogenesis (cell of origin or differentiation state)--including chordomas or adult granulosa cell tumours--and histologically defined subtypes of common cancers. Most tumour types in the first group are still clinically and biologically relevant, and have been disproportionately important as sources of insight into cancer biology. By contrast, most of those in the second group have been shown to have neither defining molecular features nor clinical utility. Omics-based analyses have splintered common cancers into a myriad of molecularly, rather than histologically, defined subsets of common cancers, many of which have immediate clinical relevance. Now, almost all rare cancers are either histomolecular entities, which often have pathognomonic mutations, or molecularly defined subsets of more common cancers. The presence of specific genetic variants provides rationale for the testing of targeted drugs in rare cancers. However, in addition to molecular alterations, it is crucial to consider the contributions of both mutation and cell context in the development, biology, and behaviour of these cancers. Patients with rare cancers are disadvantaged because of the challenge of leading clinical trials in this setting due to poor accrual. However, the number of patients with rare cancers will only increase as more molecular subsets of common cancers are identified, necessitating a shift in the focus of clinical trials and research into these cancer types, which, by epidemiological definitions, will become rare tumours. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Transit Photometry of Recently Discovered Hot Jupiters

    NASA Astrophysics Data System (ADS)

    McCloat, Sean Peter

    The University of North Dakota Space Studies Internet Observatory was used to observe the transits of hot Jupiter exoplanets. Targets for this research were selected from the list of currently confirmed exoplanets using the following criteria: radius > 0.5 Rjup, discovered since 2011, orbiting stars with apparent magnitude > 13. Eleven transits were observed distributed across nine targets with the goal of performing differential photometry for parameter refinement and transit timing variation analysis if data quality allowed. Data quality was ultimately insufficient for robust parameter refinement, but tentative calculations of mid-transit times were made of three of the observed transits. Mid-transit times for WASP-103b and WASP-48b were consistent with predictions and the existing database.

  2. Exome sequencing in schizophrenic patients with high levels of homozygosity identifies novel and extremely rare mutations in the GABA/glutamatergic pathways.

    PubMed

    Giacopuzzi, Edoardo; Gennarelli, Massimo; Minelli, Alessandra; Gardella, Rita; Valsecchi, Paolo; Traversa, Michele; Bonvicini, Cristian; Vita, Antonio; Sacchetti, Emilio; Magri, Chiara

    2017-01-01

    Inbreeding is a known risk factor for recessive Mendelian diseases and previous studies have suggested that it could also play a role in complex disorders, such as psychiatric diseases. Recent inbreeding results in the presence of long runs of homozygosity (ROHs) along the genome, which are also defined as autozygosity regions. Genetic variants in these regions have two alleles that are identical by descent, thus increasing the odds of bearing rare recessive deleterious mutations due to a homozygous state. A recent study showed a suggestive enrichment of long ROHs in schizophrenic patients, suggesting that recent inbreeding could play a role in the disease. To better understand the impact of autozygosity on schizophrenia risk, we selected, from a cohort of 180 Italian patients, seven subjects with extremely high numbers of large ROHs that were likely due to recent inbreeding and characterized the mutational landscape within their ROHs using Whole Exome Sequencing and, gene set enrichment analysis. We identified a significant overlap (17%; empirical p-value = 0.0171) between genes inside ROHs affected by low frequency functional homozygous variants (107 genes) and the group of most promising candidate genes mutated in schizophrenia. Moreover, in four patients, we identified novel and extremely rare damaging mutations in the genes involved in neurodevelopment (MEGF8) and in GABA/glutamatergic synaptic transmission (GAD1, FMN1, ANO2). These results provide insights into the contribution of rare recessive mutations and inbreeding as risk factors for schizophrenia. ROHs that are likely due to recent inbreeding harbor a combination of predisposing low-frequency variants and extremely rare variants that have a high impact on pivotal biological pathways implicated in the disease. In addition, this study confirms that focusing on patients with high levels of homozygosity could be a useful prioritization strategy for discovering new high-impact mutations in genetically

  3. Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity.

    PubMed

    Katrancha, Sara M; Wu, Yi; Zhu, Minsheng; Eipper, Betty A; Koleske, Anthony J; Mains, Richard E

    2017-12-01

    Bipolar disorder, schizophrenia, autism and intellectual disability are complex neurodevelopmental disorders, debilitating millions of people. Therapeutic progress is limited by poor understanding of underlying molecular pathways. Using a targeted search, we identified an enrichment of de novo mutations in the gene encoding the 330-kDa triple functional domain (TRIO) protein associated with neurodevelopmental disorders. By generating multiple TRIO antibodies, we show that the smaller TRIO9 isoform is the major brain protein product, and its levels decrease after birth. TRIO9 contains two guanine nucleotide exchange factor (GEF) domains with distinct specificities: GEF1 activates both Rac1 and RhoG; GEF2 activates RhoA. To understand the impact of disease-associated de novo mutations and other rare sequence variants on TRIO function, we utilized two FRET-based biosensors: a Rac1 biosensor to study mutations in TRIO (T)GEF1, and a RhoA biosensor to study mutations in TGEF2. We discovered that one autism-associated de novo mutation in TGEF1 (K1431M), at the TGEF1/Rac1 interface, markedly decreased its overall activity toward Rac1. A schizophrenia-associated rare sequence variant in TGEF1 (F1538Intron) was substantially less active, normalized to protein level and expressed poorly. Overall, mutations in TGEF1 decreased GEF1 activity toward Rac1. One bipolar disorder-associated rare variant (M2145T) in TGEF2 impaired inhibition by the TGEF2 pleckstrin-homology domain, resulting in dramatically increased TGEF2 activity. Overall, genetic damage to both TGEF domains altered TRIO catalytic activity, decreasing TGEF1 activity and increasing TGEF2 activity. Importantly, both GEF changes are expected to decrease neurite outgrowth, perhaps consistent with their association with neurodevelopmental disorders. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. An early sophisticated East Polynesian voyaging canoe discovered on New Zealand's coast

    PubMed Central

    Johns, Dilys A.; Irwin, Geoffrey J.; Sung, Yun K.

    2014-01-01

    The colonization of the islands of East Polynesia was a remarkable episode in the history of human migration and seafaring. We report on an ocean-sailing canoe dating from close to that time. A large section of a complex composite canoe was discovered recently at Anaweka on the New Zealand coast. The canoe dates to approximately A.D. 1400 and was contemporary with continuing interisland voyaging. It was built in New Zealand as an early adaptation to a new environment, and a sea turtle carved on its hull makes symbolic connections with wider Polynesian culture and art. We describe the find and identify and radiocarbon date the construction materials. We present a reconstruction of the whole canoe and compare it to another early canoe previously discovered in the Society Islands. PMID:25267657

  5. Discovering Weighted Patterns in Intron Sequences Using Self-Adaptive Harmony Search and Back-Propagation Algorithms

    PubMed Central

    Wang, Chia-Ming; Liou, Sing-Wu

    2013-01-01

    A hybrid self-adaptive harmony search and back-propagation mining system was proposed to discover weighted patterns in human intron sequences. By testing the weights under a lazy nearest neighbor classifier, the numerical results revealed the significance of these weighted patterns. Comparing these weighted patterns with the popular intron consensus model, it is clear that the discovered weighted patterns make originally the ambiguous 5SS and 3SS header patterns more specific and concrete. PMID:23737711

  6. Rare variants and cardiovascular disease.

    PubMed

    Wain, Louise V

    2014-09-01

    Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in the Western world. Large genome-wide association studies (GWASs) of coronary artery disease, myocardial infarction, stroke and dilated cardiomyopathy have identified a number of common genetic variants with modest effects on disease risk. Similarly, studies of important modifiable risk factors of CVD have identified a large number of predominantly common variant associations, for example, with blood pressure and blood lipid levels. In each case, despite the often large numbers of loci identified, only a small proportion of the phenotypic variance is explained. It has been hypothesised that rare variants with large effects may account for some of the missing variance but large-scale studies of rare variation are in their infancy for cardiovascular traits and have yet to produce fruitful results. Studies of monogenic CVDs, inherited disorders believed to be entirely driven by individual rare mutations, have highlighted genes that play a key role in disease aetiology. In this review, we discuss how findings from studies of rare variants in monogenic disease and GWAS of predominantly common variants are converging to provide further insight into biological disease mechanisms. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Discovering Self: Childbearing Adolescents' Maternal Identity.

    PubMed

    Macintosh, Janelle; Callister, Lynn Clark

    2015-01-01

    Adolescent pregnancy and motherhood have long been a topic of interest for many healthcare professionals. However, there are limited data on how childbearing adolescents incorporate motherhood identity into their sense of self. The purpose of this study was to explore how childbearing adolescents perceive motherhood as becoming part of their personal identity. This qualitative study using ethnographic data collection involved 7 months of observation, interaction, and interviews. Data were collected from nine expectant adolescents during in-depth interviews. All participants were patients at a teen mother and child clinic staffed by certified nurse midwives and a pediatrician. Narrative content analysis revealed the overall theme of discovering self, with three major themes: confirming the pregnancy, the loss of my body, and imagining my child in my arms. Adolescent mothers may need assistance to construct their maternal identity in order to strengthen self-perceptions and improve maternal/child outcomes.

  8. Rare earths, the lanthanides, yttrium and scandium

    USGS Publications Warehouse

    Bedinger, G.; Bleiwas, D.

    2012-01-01

    In 2011, rare earths were recovered from bastnasite concentrates at the Mountain Pass Mine in California. Consumption of refined rare-earth products decreased in 2011 from 2010. U.S. rare-earth imports originated primarily from China, with lesser amounts from Austria, Estonia, France and Japan. The United States imported all of its demand for yttrium metal and yttrium compounds, with most of it originating from China. Scandium was imported in various forms and processed domestically.

  9. Discovering Multimodal Behavior in Ms. Pac-Man through Evolution of Modular Neural Networks.

    PubMed

    Schrum, Jacob; Miikkulainen, Risto

    2016-03-12

    Ms. Pac-Man is a challenging video game in which multiple modes of behavior are required: Ms. Pac-Man must escape ghosts when they are threats and catch them when they are edible, in addition to eating all pills in each level. Past approaches to learning behavior in Ms. Pac-Man have treated the game as a single task to be learned using monolithic policy representations. In contrast, this paper uses a framework called Modular Multi-objective NEAT (MM-NEAT) to evolve modular neural networks. Each module defines a separate behavior. The modules are used at different times according to a policy that can be human-designed (i.e. Multitask) or discovered automatically by evolution. The appropriate number of modules can be fixed or discovered using a genetic operator called Module Mutation. Several versions of Module Mutation are evaluated in this paper. Both fixed modular networks and Module Mutation networks outperform monolithic networks and Multitask networks. Interestingly, the best networks dedicate modules to critical behaviors (such as escaping when surrounded after luring ghosts near a power pill) that do not follow the customary division of the game into chasing edible and escaping threat ghosts. The results demonstrate that MM-NEAT can discover interesting and effective behavior for agents in challenging games.

  10. Discovering Multimodal Behavior in Ms. Pac-Man through Evolution of Modular Neural Networks

    PubMed Central

    Schrum, Jacob; Miikkulainen, Risto

    2015-01-01

    Ms. Pac-Man is a challenging video game in which multiple modes of behavior are required: Ms. Pac-Man must escape ghosts when they are threats and catch them when they are edible, in addition to eating all pills in each level. Past approaches to learning behavior in Ms. Pac-Man have treated the game as a single task to be learned using monolithic policy representations. In contrast, this paper uses a framework called Modular Multi-objective NEAT (MM-NEAT) to evolve modular neural networks. Each module defines a separate behavior. The modules are used at different times according to a policy that can be human-designed (i.e. Multitask) or discovered automatically by evolution. The appropriate number of modules can be fixed or discovered using a genetic operator called Module Mutation. Several versions of Module Mutation are evaluated in this paper. Both fixed modular networks and Module Mutation networks outperform monolithic networks and Multitask networks. Interestingly, the best networks dedicate modules to critical behaviors (such as escaping when surrounded after luring ghosts near a power pill) that do not follow the customary division of the game into chasing edible and escaping threat ghosts. The results demonstrate that MM-NEAT can discover interesting and effective behavior for agents in challenging games. PMID:27030803

  11. Lessons from rare diseases of cartilage and bone.

    PubMed

    Gallagher, James A; Ranganath, Lakshminarayan R; Boyde, Alan

    2015-06-01

    Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of more common disorders and identify potential therapeutic targets. Lessons from rare bone diseases contributed to the development of the most successful class of bone active agents, the bisphosphonates. More recent research on rare bone diseases has helped elucidate key pathways and identify new targets in bone resorption and bone formation including cathepsin K and sclerostin, for which drugs are now in clinical trials. By contrast, there has been much less focus on rare cartilage diseases and osteoarthritis (OA) remains a common disease with no effective therapy. Investigation of rare cartilage syndromes is identifying new potential targets in OA including GDF5 and lubricin. Research on the arthropathy of the ultra-rare disease alkaptonuria has identified several new features of the OA phenotype, including high density mineralized protrusions (HDMPs) which constitute a newly identified mechanism of joint destruction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. PubMed on Tap: discovering design principles for online information delivery to handheld computers.

    PubMed

    Hauser, Susan E; Demner-Fushman, Dina; Ford, Glenn; Thoma, George R

    2004-01-01

    Online access to biomedical information from handheld computers will be a valuable adjunct to other popular medical applications if information delivery systems are designed with handheld computers in mind. The goal of this project is to discover design principles to facilitate practitioners' access to online medical information at the point-of-care. A prototype system was developed to serve as a testbed for this research. Using the testbed, an initial evaluation has yielded several user interface design principles. Continued research is expected to discover additional user interface design principles as well as guidelines for results organization and system performance

  13. Rare Cancers Europe (RCE) methodological recommendations for clinical studies in rare cancers: a European consensus position paper.

    PubMed

    Casali, P G; Bruzzi, P; Bogaerts, J; Blay, J-Y

    2015-02-01

    While they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in clinical studies on rare cancers, as well as adaptive trials in general, with their inherent potential of flexibility when properly applied. While clinical studies are the mainstay to test hypotheses, the potential of electronic patient records should be exploited to generate new hypotheses, to create external controls for future studies (when internal controls are unpractical), to study effectiveness of new treatments in real conditions. Framework study protocols in specific rare cancers to sequentially test sets of new agents, as from the early post-phase I development stage, should be encouraged. Also the compassionate and the off-label settings should be exploited to generate new evidence, and flexible regulatory innovations such as adaptive licensing could convey new agents early to rare cancer patients, while generating evidence. Though validation of surrogate end points is problematic in rare cancers, the use of an updated notion of tumor response may be of great value in the single patient to optimize the use of therapies, all the more the new ones. Disease-based communities, involving clinicians and patients, should be regularly consulted by regulatory bodies when setting their policies on drug approval and reimbursement in specific rare cancers. © The Author 2014

  14. The rare-earth elements: Vital to modern technologies and lifestyles

    USGS Publications Warehouse

    Van Gosen, Bradley S.; Verplanck, Philip L.; Long, Keith R.; Gambogi, Joseph; Seal, Robert R.

    2014-01-01

    Until recently, the rare-earth elements (REEs) were familiar to a relatively small number of people, such as chemists, geologists, specialized materials scientists, and engineers. In the 21st century, the REEs have gained visibility through many media outlets because of (1) the public has recognized the critical, specialized properties that REEs contribute to modern technology, as well as (2) China's dominance in production and supply of the REEs and (3) international dependence on China for the majority of the world's REE supply.Since the late 1990s, China has provided 85–95 percent of the world’s REEs. In 2010, China announced their intention to reduce REE exports. During this timeframe, REE use increased substantially. REEs are used as components in high technology devices, including smart phones, digital cameras, computer hard disks, fluorescent and light-emitting-diode (LED) lights, flat screen televisions, computer monitors, and electronic displays. Large quantities of some REEs are used in clean energy and defense technologies. Because of the many important uses of REEs, nations dependent on new technologies, such as Japan, the United States, and members of the European Union, reacted with great concern to China’s intent to reduce its REE exports. Consequently, exploration activities intent on discovering economic deposits of REEs and bringing them into production have increased.

  15. 40 CFR 721.6005 - Rare earth phosphate (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Rare earth phosphate (generic). 721... Substances § 721.6005 Rare earth phosphate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as rare earth phophate (PMNs P-99...

  16. 40 CFR 721.6005 - Rare earth phosphate (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Rare earth phosphate (generic). 721... Substances § 721.6005 Rare earth phosphate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as rare earth phophate (PMNs P-99...

  17. 40 CFR 721.6005 - Rare earth phosphate (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Rare earth phosphate (generic). 721... Substances § 721.6005 Rare earth phosphate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as rare earth phophate (PMNs P-99...

  18. 40 CFR 721.6005 - Rare earth phosphate (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Rare earth phosphate (generic). 721... Substances § 721.6005 Rare earth phosphate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as rare earth phophate (PMNs P-99...

  19. 40 CFR 721.6005 - Rare earth phosphate (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Rare earth phosphate (generic). 721... Substances § 721.6005 Rare earth phosphate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as rare earth phophate (PMNs P-99...

  20. Rare earth element scavenging in seawater

    NASA Astrophysics Data System (ADS)

    Byrne, Robert H.; Kim, Ki-Hyun

    1990-10-01

    Examinations of rare earth element (REE) adsorption in seawater, using a variety of surface-types, indicated that, for most surfaces, light rare earth elements (LREEs) are preferentially adsorbed compared to the heavy rare earths (HREEs). Exceptions to this behavior were observed only for silica phases (glass surfaces, acid-cleaned diatomaceous earth, and synthetic SiO 2). The affinity of the rare earths for surfaces can be strongly affected by thin organic coatings. Glass surfaces which acquired an organic coating through immersion in Tampa Bay exhibited adsorptive behavior typical of organic-rich, rather than glass, surfaces. Models of rare earth distributions between seawater and carboxylate-rich surfaces indicate that scavenging processes which involve such surfaces should exhibit a strong dependence on pH and carbonate complexation. Scavenging models involving carboxylate surfaces produce relative REE abundance patterns in good general agreement with observed shale-normalized REE abundances in seawater. Scavenging by carboxylate-rich surfaces should produce HREE enrichments in seawater relative to the LREEs and may produce enrichments of lanthanum relative to its immediate trivalent neighbors. Due to the origin of distribution coefficients as a difference between REE solution complexation (which increases strongly with atomic number) and surface complexation (which apparently also increases with atomic number) the relative solution abundance patterns of the REEs produced by scavenging reactions can be quite complex.

  1. Using RSAT oligo-analysis and dyad-analysis tools to discover regulatory signals in nucleic sequences.

    PubMed

    Defrance, Matthieu; Janky, Rekin's; Sand, Olivier; van Helden, Jacques

    2008-01-01

    This protocol explains how to discover functional signals in genomic sequences by detecting over- or under-represented oligonucleotides (words) or spaced pairs thereof (dyads) with the Regulatory Sequence Analysis Tools (http://rsat.ulb.ac.be/rsat/). Two typical applications are presented: (i) predicting transcription factor-binding motifs in promoters of coregulated genes and (ii) discovering phylogenetic footprints in promoters of orthologous genes. The steps of this protocol include purging genomic sequences to discard redundant fragments, discovering over-represented patterns and assembling them to obtain degenerate motifs, scanning sequences and drawing feature maps. The main strength of the method is its statistical ground: the binomial significance provides an efficient control on the rate of false positives. In contrast with optimization-based pattern discovery algorithms, the method supports the detection of under- as well as over-represented motifs. Computation times vary from seconds (gene clusters) to minutes (whole genomes). The execution of the whole protocol should take approximately 1 h.

  2. "Discovering the Cell": An Educational Game about Cell and Molecular Biology

    ERIC Educational Resources Information Center

    Spiegel, Carolina N.; Alves, Gutemberg G.; Cardona, Tania da S.; Melim, Leandra M. C.; Luz, Mauricio R. M. P.; Araujo-Jorge, Tania C.; Henriques-Pons, Andrea

    2008-01-01

    The role of games within education becomes clearer as students become more active and are able to take decisions, solve problems and react to the results of those decisions. The educational board game "Discovering the Cell" ("Celula Adentro"), is based on problem-solving learning. This investigative game attempts to stimulate…

  3. RAS signalling in energy metabolism and rare human diseases.

    PubMed

    Dard, L; Bellance, N; Lacombe, D; Rossignol, R

    2018-05-08

    The RAS pathway is a highly conserved cascade of protein-protein interactions and phosphorylation that is at the heart of signalling networks that govern proliferation, differentiation and cell survival. Recent findings indicate that the RAS pathway plays a role in the regulation of energy metabolism via the control of mitochondrial form and function but little is known on the participation of this effect in RAS-related rare human genetic diseases. Germline mutations that hyperactivate the RAS pathway have been discovered and linked to human developmental disorders that are known as RASopathies. Individuals with RASopathies, which are estimated to affect approximately 1/1000 human birth, share many overlapping characteristics, including cardiac malformations, short stature, neurocognitive impairment, craniofacial dysmorphy, cutaneous, musculoskeletal, and ocular abnormalities, hypotonia and a predisposition to developing cancer. Since the identification of the first RASopathy, type 1 neurofibromatosis (NF1), which is caused by the inactivation of neurofibromin 1, several other syndromes have been associated with mutations in the core components of the RAS-MAPK pathway. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), which was formerly called LEOPARD syndrome, Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Legius syndrome (LS) and capillary malformation-arteriovenous malformation syndrome (CM-AVM). Here, we review current knowledge about the bioenergetics of the RASopathies and discuss the molecular control of energy homeostasis and mitochondrial physiology by the RAS pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. DISCOVER-AQ SJV Surface Measurements and Initial Comparisons with Photochemical Model Simulations

    EPA Science Inventory

    NASA’s DISCOVER-AQ (Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality) campaign studied the air quality throughout California’s San Joaquin Valley (SJV) during January and February of 2013. The SJV is a...

  5. A Discovery Resource of Rare Copy Number Variations in Individuals with Autism Spectrum Disorder

    PubMed Central

    Prasad, Aparna; Merico, Daniele; Thiruvahindrapuram, Bhooma; Wei, John; Lionel, Anath C.; Sato, Daisuke; Rickaby, Jessica; Lu, Chao; Szatmari, Peter; Roberts, Wendy; Fernandez, Bridget A.; Marshall, Christian R.; Hatchwell, Eli; Eis, Peggy S.; Scherer, Stephen W.

    2012-01-01

    The identification of rare inherited and de novo copy number variations (CNVs) in human subjects has proven a productive approach to highlight risk genes for autism spectrum disorder (ASD). A variety of microarrays are available to detect CNVs, including single-nucleotide polymorphism (SNP) arrays and comparative genomic hybridization (CGH) arrays. Here, we examine a cohort of 696 unrelated ASD cases using a high-resolution one-million feature CGH microarray, the majority of which were previously genotyped with SNP arrays. Our objective was to discover new CNVs in ASD cases that were not detected by SNP microarray analysis and to delineate novel ASD risk loci via combined analysis of CGH and SNP array data sets on the ASD cohort and CGH data on an additional 1000 control samples. Of the 615 ASD cases analyzed on both SNP and CGH arrays, we found that 13,572 of 21,346 (64%) of the CNVs were exclusively detected by the CGH array. Several of the CGH-specific CNVs are rare in population frequency and impact previously reported ASD genes (e.g., NRXN1, GRM8, DPYD), as well as novel ASD candidate genes (e.g., CIB2, DAPP1, SAE1), and all were inherited except for a de novo CNV in the GPHN gene. A functional enrichment test of gene-sets in ASD cases over controls revealed nucleotide metabolism as a potential novel pathway involved in ASD, which includes several candidate genes for follow-up (e.g., DPYD, UPB1, UPP1, TYMP). Finally, this extensively phenotyped and genotyped ASD clinical cohort serves as an invaluable resource for the next step of genome sequencing for complete genetic variation detection. PMID:23275889

  6. Astronomers Discover Fastest-Spinning Pulsar

    NASA Astrophysics Data System (ADS)

    2006-01-01

    Astronomers using the National Science Foundation's Robert C. Byrd Green Bank Telescope have discovered the fastest-spinning neutron star ever found, a 20-mile-diameter superdense pulsar whirling faster than the blades of a kitchen blender. Their work yields important new information about the nature of one of the most exotic forms of matter known in the Universe. Pulsar Graphic Pulsars Are Spinning Neutron Stars CREDIT: Bill Saxton, NRAO/AUI/NSF (Click on image for larger version) "We believe that the matter in neutron stars is denser than an atomic nucleus, but it is unclear by how much. Our observations of such a rapidly rotating star set a hard upper limit on its size, and hence on how dense the star can be.," said Jason Hessels, a graduate student at McGill University in Montreal. Hessels and his colleagues presented their findings to the American Astronomical Society's meeting in Washington, DC. Pulsars are spinning neutron stars that sling "lighthouse beams" of radio waves or light around as they spin. A neutron star is what is left after a massive star explodes at the end of its "normal" life. With no nuclear fuel left to produce energy to offset the stellar remnant's weight, its material is compressed to extreme densities. The pressure squeezes together most of its protons and electrons to form neutrons; hence, the name "neutron star." "Neutron stars are incredible laboratories for learning about the physics of the fundamental particles of nature, and this pulsar has given us an important new limit," explained Scott Ransom, an astronomer at the National Radio Astronomy Observatory and one of Hessels' collaborators on this work. The scientists discovered the pulsar, named PSR J1748-2446ad, in a globular cluster of stars called Terzan 5, located some 28,000 light-years from Earth in the constellation Sagittarius. The newly-discovered pulsar is spinning 716 times per second, or at 716 Hertz (Hz), readily beating the previous record of 642 Hz from a pulsar

  7. Rare Earth Optical Temperature Sensor

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L. (Inventor); Jenkins, Phillip (Inventor)

    2004-01-01

    A rare earth optical temperature sensor is disclosed for measuring high temperatures. Optical temperature sensors exist that channel emissions from a sensor to a detector using a light pipe. The invention uses a rare earth emitter to transform the sensed thermal energy into a narrow band width optical signal that travels to a detector using a light pipe. An optical bandpass filter at the detector removes any noise signal outside of the band width of the signal from the emitter.

  8. Discovering Pediatric Asthma Phenotypes on the Basis of Response to Controller Medication Using Machine Learning.

    PubMed

    Ross, Mindy K; Yoon, Jinsung; van der Schaar, Auke; van der Schaar, Mihaela

    2018-01-01

    Pediatric asthma has variable underlying inflammation and symptom control. Approaches to addressing this heterogeneity, such as clustering methods to find phenotypes and predict outcomes, have been investigated. However, clustering based on the relationship between treatment and clinical outcome has not been performed, and machine learning approaches for long-term outcome prediction in pediatric asthma have not been studied in depth. Our objectives were to use our novel machine learning algorithm, predictor pursuit (PP), to discover pediatric asthma phenotypes on the basis of asthma control in response to controller medications, to predict longitudinal asthma control among children with asthma, and to identify features associated with asthma control within each discovered pediatric phenotype. We applied PP to the Childhood Asthma Management Program study data (n = 1,019) to discover phenotypes on the basis of asthma control between assigned controller therapy groups (budesonide vs. nedocromil). We confirmed PP's ability to discover phenotypes using the Asthma Clinical Research Network/Childhood Asthma Research and Education network data. We next predicted children's asthma control over time and compared PP's performance with that of traditional prediction methods. Last, we identified clinical features most correlated with asthma control in the discovered phenotypes. Four phenotypes were discovered in both datasets: allergic not obese (A + /O - ), obese not allergic (A - /O + ), allergic and obese (A + /O + ), and not allergic not obese (A - /O - ). Of the children with well-controlled asthma in the Childhood Asthma Management Program dataset, we found more nonobese children treated with budesonide than with nedocromil (P = 0.015) and more obese children treated with nedocromil than with budesonide (P = 0.008). Within the obese group, more A + /O + children's asthma was well controlled with nedocromil than with budesonide (P = 0.022) or with placebo

  9. Drugs for rare disorders.

    PubMed

    Cremers, Serge; Aronson, Jeffrey K

    2017-08-01

    Estimates of the frequencies of rare disorders vary from country to country; the global average defined prevalence is 40 per 100 000 (0.04%). Some occur in only one or a few patients. However, collectively rare disorders are fairly common, affecting 6-8% of the US population, or about 30 million people, and a similar number in the European Union. Most of them affect children and most are genetically determined. Diagnosis can be difficult, partly because of variable presentations and partly because few clinicians have experience of individual rare disorders, although they may be assisted by searching databases. Relatively few rare disorders have specific pharmacological treatments (so-called orphan drugs), partly because of difficulties in designing trials large enough to determine benefits and harms alike. Incentives have been introduced to encourage the development of orphan drugs, including tax credits and research aids, simplification of marketing authorization procedures and exemption from fees, and extended market exclusivity. Consequently, the number of applications for orphan drugs has grown, as have the costs of using them, so much so that treatments may not be cost-effective. It has therefore been suggested that not-for-profit organizations that are socially motivated to reduce those costs should be tasked with producing them. A growing role for patient organizations, improved clinical and translational infrastructures, and developments in genetics have also contributed to successful drug development. The translational discipline of clinical pharmacology is an essential component in drug development, including orphan drugs. Clinical pharmacologists, skilled in basic pharmacology and its links to clinical medicine, can be involved at all stages. They can contribute to the delineation of genetic factors that determine clinical outcomes of pharmacological interventions, develop biomarkers, design and perform clinical trials, assist regulatory decision

  10. An Overview of Rare Earth Science and Technology

    NASA Astrophysics Data System (ADS)

    Gschneidner, Karl, Jr.

    2012-02-01

    Currently rare earth science and technology is robust: this includes all the major branches of science -- biochemistry, chemistry, materials and physics. There are, however, currently some anomalies and distortions especially in the technology and applications sector of the rare earth field, which is caused by the dominance of China on the sales of rare earths and rare earth containing products. For the past 5 to 10 years ˜95% of rare earths utilized in commerce came from China. Although Chinese actions have lead to sudden and large price spikes and export embargoes, the rare earths are still available but at a higher cost. The start up of production in 2011 at mines in the USA and Australia will alleviate this situation in about two years. Basic and applied research on the condensed matter physics/materials science has hardly been impacted by these events, but new research opportunities are opening up especially with regard to the USA's military and energy security. Magnets seems to be the hottest topic, but research on battery materials, phosphors and catalysts are also (or should be) strongly considered.

  11. Discovering, Indexing and Interlinking Information Resources

    PubMed Central

    Celli, Fabrizio; Keizer, Johannes; Jaques, Yves; Konstantopoulos, Stasinos; Vudragović, Dušan

    2015-01-01

    The social media revolution is having a dramatic effect on the world of scientific publication. Scientists now publish their research interests, theories and outcomes across numerous channels, including personal blogs and other thematic web spaces where ideas, activities and partial results are discussed. Accordingly, information systems that facilitate access to scientific literature must learn to cope with this valuable and varied data, evolving to make this research easily discoverable and available to end users. In this paper we describe the incremental process of discovering web resources in the domain of agricultural science and technology. Making use of Linked Open Data methodologies, we interlink a wide array of custom-crawled resources with the AGRIS bibliographic database in order to enrich the user experience of the AGRIS website. We also discuss the SemaGrow Stack, a query federation and data integration infrastructure used to estimate the semantic distance between crawled web resources and AGRIS. PMID:26834982

  12. Michael Maier--nine newly discovered letters.

    PubMed

    Lenke, Nils; Roudet, Nicolas; Tilton, Hereward

    2014-02-01

    The authors provide a transcription, translation, and evaluation of nine newly discovered letters from the alchemist Michael Maier (1568-1622) to Gebhardt Johann von Alvensleben (1576-1631), a noble landholder in the vicinity of Magdeburg. Stemming from the final year of his life, this correspondence casts new light on Maier's biography, detailing his efforts to secure patronage amid the financial crisis of the early Thirty Years' War. While his ill-fated quest to perfect potable gold continued to form the central focus of his patronage suits, Maier also offered his services in several arts that he had condemned in his printed works, namely astrology and "supernatural" magic. Remarks concerning his previously unknown acquaintance with Heinrich Khunrath call for a re-evaluation of Maier's negotiation of the discursive boundaries between Lutheran orthodoxy and Paracelsianism. The letters also reveal Maier's substantial contribution to a work previously ascribed solely to the English alchemist Francis Anthony.

  13. [A rare form of granuloma annulare].

    PubMed

    Bogdanowski, T; Wygledowska-Kania, M

    1995-01-01

    We present a four-year-old girl with a doubly rare form of granuloma annulare with non-typical localisation of superficial nodules on the palms and predisposition to ulceration which is very rare in this type of superficial nodules. The diagnosis was proved by histological examination. After the local cryotherapy (ethyl chloride) the lesions almost completely disappeared.

  14. Ames Lab 101: Rare-Earth Recycling

    ScienceCinema

    Ryan Ott

    2017-12-22

    Recycling keeps paper, plastics, and even jeans out of landfills. Could recycling rare-earth magnets do the same? Perhaps, if the recycling process can be improved. Scientists at the U.S. Department of Energy's Ames Laboratory are working to more effectively remove the neodymium, a rare earth, from the mix of other materials in a magnet.

  15. Improving the Interpretability of Classification Rules Discovered by an Ant Colony Algorithm: Extended Results.

    PubMed

    Otero, Fernando E B; Freitas, Alex A

    2016-01-01

    Most ant colony optimization (ACO) algorithms for inducing classification rules use a ACO-based procedure to create a rule in a one-at-a-time fashion. An improved search strategy has been proposed in the cAnt-Miner[Formula: see text] algorithm, where an ACO-based procedure is used to create a complete list of rules (ordered rules), i.e., the ACO search is guided by the quality of a list of rules instead of an individual rule. In this paper we propose an extension of the cAnt-Miner[Formula: see text] algorithm to discover a set of rules (unordered rules). The main motivations for this work are to improve the interpretation of individual rules by discovering a set of rules and to evaluate the impact on the predictive accuracy of the algorithm. We also propose a new measure to evaluate the interpretability of the discovered rules to mitigate the fact that the commonly used model size measure ignores how the rules are used to make a class prediction. Comparisons with state-of-the-art rule induction algorithms, support vector machines, and the cAnt-Miner[Formula: see text] producing ordered rules are also presented.

  16. Sharing Rare Attitudes Attracts.

    PubMed

    Alves, Hans

    2018-04-01

    People like others who share their attitudes. Online dating platforms as well as other social media platforms regularly rely on the social bonding power of their users' shared attitudes. However, little is known about moderating variables. In the present work, I argue that sharing rare compared with sharing common attitudes should evoke stronger interpersonal attraction among people. In five studies, I tested this prediction for the case of shared interests from different domains. I found converging evidence that people's rare compared with their common interests are especially potent to elicit interpersonal attraction. I discuss the current framework's theoretical implications for impression formation and impression management as well as its practical implications for improving online dating services.

  17. Rare genetic variants in Tunisian Jewish patients suffering from age-related macular degeneration.

    PubMed

    Pras, Eran; Kristal, Dana; Shoshany, Nadav; Volodarsky, Dina; Vulih, Inna; Celniker, Gershon; Isakov, Ofer; Shomron, Noam; Pras, Elon

    2015-07-01

    To explore the molecular basis of familial, early onset, age-related macular degeneration (AMD) with diverse phenotypes, using whole exome sequencing (WES). We performed WES on four patients (two sibs from two families) manifesting early-onset AMD and searched for disease-causing genetic variants in previously identified macular degeneration related genes. Validation studies of the variants included bioinformatics tools, segregation analysis of mutations within the families and mutation screening in an AMD cohort of patients. The index patients were in their 50s when diagnosed and displayed a wide variety of clinical AMD presentations: from limited drusen in the posterior pole to multiple basal-laminar drusen extending peripherally. Severe visual impairment due to extensive geographic atrophy and/or choroidal-neovascularisation was common by the age of 75 years. Approximately, 400 000 genomic variants for each DNA sample were included in the downstream bioinformatics analysis, which ended in the discovery of two novel variants; in one family a single bp deletion was identified in the Hemicentin (HMCN1) gene (c.4162delC), whereas in the other, a missense variant (p.V412M) in the Complement Factor-I (CFI) gene was found. Screening for these variants in a cohort of patients with AMD identified another family with the CFI variant. This report uses WES to uncover rare genetic variants in AMD. A null-variant in HMCN1 has been identified in one AMD family, and a missense variant in CFI was discovered in two other families. These variants confirm the genetic complexity and significance of rare genetic variants in the pathogenesis of AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Combined mining: discovering informative knowledge in complex data.

    PubMed

    Cao, Longbing; Zhang, Huaifeng; Zhao, Yanchang; Luo, Dan; Zhang, Chengqi

    2011-06-01

    Enterprise data mining applications often involve complex data such as multiple large heterogeneous data sources, user preferences, and business impact. In such situations, a single method or one-step mining is often limited in discovering informative knowledge. It would also be very time and space consuming, if not impossible, to join relevant large data sources for mining patterns consisting of multiple aspects of information. It is crucial to develop effective approaches for mining patterns combining necessary information from multiple relevant business lines, catering for real business settings and decision-making actions rather than just providing a single line of patterns. The recent years have seen increasing efforts on mining more informative patterns, e.g., integrating frequent pattern mining with classifications to generate frequent pattern-based classifiers. Rather than presenting a specific algorithm, this paper builds on our existing works and proposes combined mining as a general approach to mining for informative patterns combining components from either multiple data sets or multiple features or by multiple methods on demand. We summarize general frameworks, paradigms, and basic processes for multifeature combined mining, multisource combined mining, and multimethod combined mining. Novel types of combined patterns, such as incremental cluster patterns, can result from such frameworks, which cannot be directly produced by the existing methods. A set of real-world case studies has been conducted to test the frameworks, with some of them briefed in this paper. They identify combined patterns for informing government debt prevention and improving government service objectives, which show the flexibility and instantiation capability of combined mining in discovering informative knowledge in complex data.

  19. Discovering the plates boundaries in the Mediterranean sea

    NASA Astrophysics Data System (ADS)

    Marinelli, Maurizio

    2017-04-01

    During the 8th class the students learn geology. We analyze the earth's layers, the earthquakes, the volcanoes and other natural phenomena like subduction and orogeny. We start with a global study but our goal is to focus on the crust to discover the plates boundaries, particularly the boundary between Eurasian and African Plate in the Mediterranean sea. It's very simple for the students to discover all the information using the Internet or the science book, but I want to make with them an exploration of earth science with the help of the natural phenomena we studied during the year. We connect with Istituto Nazionale di Geofisica e Vulcanologia ( http://www.ingv.it/en/ ) where we can find a map with the earthquakes happened in the last years in Italy and in the Mediterranean sea and the list of the main volcanoes. In this way we can draw a map of the mediterranean plates and we can talk about the past and the future of the Mediterranean sea, Europe and Africa based on our maps and on the Alps orogeny. Using youtube we can have a confirm of our hypothesis about the future of the Mediterranean sea (https://www.youtube.com/watch?v=uGcDed4xVD4 ). A good observation for the students is given by the fact that we live in Europe but actually we stay on the African plate. The boundary is 5 km north of our school and we can go and visit the place where it is possible to see the different height of the two plates.

  20. Discovering functional modules by topic modeling RNA-Seq based toxicogenomic data.

    PubMed

    Yu, Ke; Gong, Binsheng; Lee, Mikyung; Liu, Zhichao; Xu, Joshua; Perkins, Roger; Tong, Weida

    2014-09-15

    Toxicogenomics (TGx) endeavors to elucidate the underlying molecular mechanisms through exploring gene expression profiles in response to toxic substances. Recently, RNA-Seq is increasingly regarded as a more powerful alternative to microarrays in TGx studies. However, realizing RNA-Seq's full potential requires novel approaches to extracting information from the complex TGx data. Considering read counts as the number of times a word occurs in a document, gene expression profiles from RNA-Seq are analogous to a word by document matrix used in text mining. Topic modeling aiming at to discover the latent structures in text corpora would be helpful to explore RNA-Seq based TGx data. In this study, topic modeling was applied on a typical RNA-Seq based TGx data set to discover hidden functional modules. The RNA-Seq based gene expression profiles were transformed into "documents", on which latent Dirichlet allocation (LDA) was used to build a topic model. We found samples treated by the compounds with the same modes of actions (MoAs) could be clustered based on topic similarities. The topic most relevant to each cluster was identified as a "marker" topic, which was interpreted by gene enrichment analysis with MoAs then confirmed by compound and pathways associations mined from literature. To further validate the "marker" topics, we tested topic transferability from RNA-Seq to microarrays. The RNA-Seq based gene expression profile of a topic specifically associated with peroxisome proliferator-activated receptors (PPAR) signaling pathway was used to query samples with similar expression profiles in two different microarray data sets, yielding accuracy of about 85%. This proof-of-concept study demonstrates the applicability of topic modeling to discover functional modules in RNA-Seq data and suggests a valuable computational tool for leveraging information within TGx data in RNA-Seq era.

  1. Whole-exome sequencing reveals a rare interferon gamma receptor 1 mutation associated with myasthenia gravis.

    PubMed

    Qi, Guoyan; Liu, Peng; Gu, Shanshan; Yang, Hongxia; Dong, Huimin; Xue, Yinping

    2018-04-01

    Our study is aimed to explore the underlying genetic basis of myasthenia gravis. We collected a Chinese pedigree with myasthenia gravis, and whole-exome sequencing was performed on the two affected siblings and their parents. The candidate pathogenic gene was identified by bioinformatics filtering, which was further verified by Sanger sequencing. The homozygous mutation c.G40A (p.V14M) in interferon gamma receptor 1was identified. Moreover, the mutation was also detected in 3 cases of 44 sporadic myasthenia gravis patients. The p.V14M substitution in interferon gamma receptor 1 may affect the signal peptide function and the translocation on cell membrane, which could disrupt the binding of the ligand of interferon gamma and antibody production, contributing to myasthenia gravis susceptibility. We discovered that a rare variant c.G40A in interferon gamma receptor 1 potentially contributes to the myasthenia gravis pathogenesis. Further functional studies are needed to confirm the effect of the interferon gamma receptor 1 on the myasthenia gravis phenotype.

  2. Rare Earth Elements | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    - Mineral Resources main content Rare Earth Elements Rare earth elements and the supply and demand of these deposits containing rare earth elements to meet the perceived future demand. High prices for rare earth earth element occurrences in the DGGS publications catalog. Department of Natural Resources, Division of

  3. Medicinal benefits of marine invertebrates: sources for discovering natural drug candidates.

    PubMed

    De Zoysa, Mahanama

    2012-01-01

    Marine invertebrates are one of the major groups of organisms, which could be diversified under the major taxonomic groups of Porifera, Cnidaria, Mollusca, Arthropoda, Echinodermata, and many other minor phyla. To date, range of medicinal benefits and a significant number of marine natural products (MNPs) have been discovered from marine invertebrates. Seafood diet from edible marine invertebrates such as mollusks and crustaceans has been linked with various medicinal benefits to improve human health. Among marine invertebrates, spongers from phylum Porifera is the most dominant group responsible for discovering large number of MNPs, which have been used as template to develop therapeutic drugs. MNPs isolated from invertebrates have shown wide range of therapeutic properties including antimicrobial, antioxidant, antihypertensive, anticoagulant, anticancer, anti-inflammatory, wound healing and immune modulator, and other medicinal effects. Therefore, marine invertebrates are rich sources of chemical diversity and health benefits for developing drug candidates, cosmetics, nutritional supplements, and molecular probes that can be supported to increase the healthy life span of human. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Bioleaching of rare earth elements from monazite sand.

    PubMed

    Brisson, Vanessa L; Zhuang, Wei-Qin; Alvarez-Cohen, Lisa

    2016-02-01

    Three fungal strains were found to be capable of bioleaching rare earth elements from monazite, a rare earth phosphate mineral, utilizing the monazite as a phosphate source and releasing rare earth cations into solution. These organisms include one known phosphate solubilizing fungus, Aspergillus niger ATCC 1015, as well as two newly isolated fungi: an Aspergillus terreus strain ML3-1 and a Paecilomyces spp. strain WE3-F. Although monazite also contains the radioactive element Thorium, bioleaching by these fungi preferentially solubilized rare earth elements over Thorium, leaving the Thorium in the solid residual. Adjustments in growth media composition improved bioleaching performance measured as rare earth release. Cell-free spent medium generated during growth of A. terreus strain ML3-1 and Paecilomyces spp. strain WE3-F in the presence of monazite leached rare earths to concentrations 1.7-3.8 times those of HCl solutions of comparable pH, indicating that compounds exogenously released by these organisms contribute substantially to leaching. Organic acids released by the organisms included acetic, citric, gluconic, itaconic, oxalic, and succinic acids. Abiotic leaching with laboratory prepared solutions of these acids was not as effective as bioleaching or leaching with cell-free spent medium at releasing rare earths from monazite, indicating that compounds other than the identified organic acids contribute to leaching performance. © 2015 Wiley Periodicals, Inc.

  5. Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

    PubMed Central

    Bagyinszky, Eva; Youn, Young Chul; An, Seong Soo A; Kim, SangYun

    2016-01-01

    Alzheimer’s disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People’s Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People’s Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention. PMID:27799753

  6. [Rare causes of childhood leukocoria].

    PubMed

    Diagne, J-P; Sow, A S; Ka, A M; Wane, A M; Ndoye Roth, P A; Ba, E A; De Medeiros, M E; Ndiaye, J M; Diallo, H M; Kane, H; Sow, S; Nguer, M; Sy, E M; Ndiaye, P A

    2017-10-01

    The purpose was to record the causes of leukocoria among children under 10years of age and to determine the proportion of rare causes of leukocoria. This retrospective study was conducted over a period of ten years, from January 1, 2004 to December 31, 2013, in patients under 10years of age who were referred for leukocoria. Leukocoria represented one of the ten reasons for consultation among children under 10years of age. The mean age of our patients was 42.5months. In 76 % of cases, the leukocoria patients were children under 6years of age. Male patients were affected more commonly, with a sex-ratio of 1.5. Patients coming from Dakar and its suburbs represented two thirds of the total. Bilateral involvement represented 53.7 % of the total. Cataracts were responsible for 74.3 % of cases, retinoblastoma 20.58 %, retinal detachment 0.96 %, retinopathy of prematurity 0.96 %, pupillary membrane persistence 0.96 %, persistent hyperplastic primary vitreous 0.64 %, endophthalmitis 0.64 %, optic nerve coloboma 0.32 %, iris heterochromia 0.32 % and ametropia 0.32 %. The total percentage of rare causes was 5.12 % in our study, including one case of hyperopia. These etiologies, although rare, do exist. Rare causes of leukocoria require special attention. The discovery of leukocoria necessitates rigorous etiological work-up. Ametropia must be a diagnosis of exclusion. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. A comparison of the IGBP DISCover and University of Maryland 1 km global land cover products

    USGS Publications Warehouse

    Hansen, M.C.; Reed, B.

    2000-01-01

    Two global 1 km land cover data sets derived from 1992-1993 Advanced Very High Resolution Radiometer (AVHRR) data are currently available, the International Geosphere-Biosphere Programme Data and Information System (IGBP-DIS) DISCover and the University of Maryland (UMd) 1 km land cover maps. This paper makes a preliminary comparison of the methodologies and results of the two products. The DISCover methodology employed an unsupervised clustering classification scheme on a per-continent basis using 12 monthly maximum NDVI composites as inputs. The UMd approach employed a supervised classification tree method in which temporal metrics derived from all AVHRR bands and the NDVI were used to predict class membership across the entire globe. The DISCover map uses the IGBP classification scheme, while the UMd map employs a modified IGBP scheme minus the classes of permanent wetlands, cropland/natural vegetation mosaic and ice and snow. Global area totals of aggregated vegetation types are very similar and have a per-pixel agreement of 74%. For tall versus short/no vegetation, the per-pixel agreement is 84%. For broad vegetation types, core areas map similarly, while transition zones around core areas differ significantly. This results in high regional variability between the maps. Individual class agreement between the two 1 km maps is 49%. Comparison of the maps at a nominal 0.5 resolution with two global ground-based maps shows an improvement of thematic concurrency of 46% when viewing average class agreement. The absence of the cropland mosaic class creates a difficulty in comparing the maps, due to its significant extent in the DISCover map. The DISCover map, in general, has more forest, while the UMd map has considerably more area in the intermediate tree cover classes of woody savanna/ woodland and savanna/wooded grassland.

  8. Discovering the Art of Mathematics: Using String Art to Investigate Calculus

    ERIC Educational Resources Information Center

    von Renesse, Christine; Ecke, Volker

    2016-01-01

    One goal of our Discovering the Art of Mathematics project is to empower students in the liberal arts to become confident creators of art and imaginative creators of mathematics. In this paper, we describe our experience with using string art to guide liberal arts students in exploring ideas of calculus. We provide excerpts from our inquiry-based…

  9. Evaluation of the Discover Drug Education Curriculum for Grades K-4.

    ERIC Educational Resources Information Center

    Adams, Ronald D.; Butler, Joan M.

    A major purpose of this study was to establish and test a procedure for evaluating drug education curricula that allows for a more objective view of the effectiveness of drug education materials and the instructional delivery system. A major focus of the study was to determine the extent to which the Discover Curriculum affected student outcomes.…

  10. Strong self-limitation promotes the persistence of rare species.

    PubMed

    Yenni, Glenda; Adler, Peter B; Ernest, S K Morgan

    2012-03-01

    Theory has recognized a combination of niche and neutral processes each contributing, with varying importance, to species coexistence. However, long-term persistence of rare species has been difficult to produce in trait-based models of coexistence that incorporate stochastic dynamics, raising questions about how rare species persist despite such variability. Following recent evidence that rare species may experience significantly different population dynamics than dominant species, we use a plant community model to simulate the effect of disproportionately strong negative frequency dependence on the long-term persistence of the rare species in a simulated community. This strong self-limitation produces long persistence times for the rare competitors, which otherwise succumb quickly to stochastic extinction. The results suggest that the mechanism causing species to be rare in this case is the same mechanism allowing those species to persist.

  11. RareVariantVis: new tool for visualization of causative variants in rare monogenic disorders using whole genome sequencing data.

    PubMed

    Stokowy, Tomasz; Garbulowski, Mateusz; Fiskerstrand, Torunn; Holdhus, Rita; Labun, Kornel; Sztromwasser, Pawel; Gilissen, Christian; Hoischen, Alexander; Houge, Gunnar; Petersen, Kjell; Jonassen, Inge; Steen, Vidar M

    2016-10-01

    The search for causative genetic variants in rare diseases of presumed monogenic inheritance has been boosted by the implementation of whole exome (WES) and whole genome (WGS) sequencing. In many cases, WGS seems to be superior to WES, but the analysis and visualization of the vast amounts of data is demanding. To aid this challenge, we have developed a new tool-RareVariantVis-for analysis of genome sequence data (including non-coding regions) for both germ line and somatic variants. It visualizes variants along their respective chromosomes, providing information about exact chromosomal position, zygosity and frequency, with point-and-click information regarding dbSNP IDs, gene association and variant inheritance. Rare variants as well as de novo variants can be flagged in different colors. We show the performance of the RareVariantVis tool in the Genome in a Bottle WGS data set. https://www.bioconductor.org/packages/3.3/bioc/html/RareVariantVis.html tomasz.stokowy@k2.uib.no Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Artificial Intelligence and NASA Data Used to Discover Eighth Planet Circling Distant Star

    NASA Image and Video Library

    2017-12-12

    Our solar system now is tied for most number of planets around a single star, with the recent discovery of an eighth planet circling Kepler-90, a Sun-like star 2,545 light years from Earth. The planet was discovered in data from NASA’s Kepler space telescope. The newly-discovered Kepler-90i -- a sizzling hot, rocky planet that orbits its star once every 14.4 days -- was found by researchers from Google and The University of Texas at Austin using machine learning. Machine learning is an approach to artificial intelligence in which computers “learn.” In this case, computers learned to identify planets by finding in Kepler data instances where the telescope recorded signals from planets beyond our solar system, known as exoplanets. Video Credit: NASA Ames Research Center / Google

  13. Using in Vitro Evolution and Whole Genome Analysis To Discover Next Generation Targets for Antimalarial Drug Discovery

    PubMed Central

    2018-01-01

    Although many new anti-infectives have been discovered and developed solely using phenotypic cellular screening and assay optimization, most researchers recognize that structure-guided drug design is more practical and less costly. In addition, a greater chemical space can be interrogated with structure-guided drug design. The practicality of structure-guided drug design has launched a search for the targets of compounds discovered in phenotypic screens. One method that has been used extensively in malaria parasites for target discovery and chemical validation is in vitro evolution and whole genome analysis (IVIEWGA). Here, small molecules from phenotypic screens with demonstrated antiparasitic activity are used in genome-based target discovery methods. In this Review, we discuss the newest, most promising druggable targets discovered or further validated by evolution-based methods, as well as some exceptions. PMID:29451780

  14. GraphTeams: a method for discovering spatial gene clusters in Hi-C sequencing data.

    PubMed

    Schulz, Tizian; Stoye, Jens; Doerr, Daniel

    2018-05-08

    Hi-C sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes. We use data obtained from Hi-C experiments to provide new evidence for the existence of spatial gene clusters. These are sets of genes with associated functionality that exhibit close proximity to each other in the spatial conformation of chromosomes across several related species. We present the first gene cluster model capable of handling spatial data. Our model generalizes a popular computational model for gene cluster prediction, called δ-teams, from sequences to graphs. Following previous lines of research, we subsequently extend our model to allow for several vertices being associated with the same label. The model, called δ-teams with families, is particular suitable for our application as it enables handling of gene duplicates. We develop algorithmic solutions for both models. We implemented the algorithm for discovering δ-teams with families and integrated it into a fully automated workflow for discovering gene clusters in Hi-C data, called GraphTeams. We applied it to human and mouse data to find intra- and interchromosomal gene cluster candidates. The results include intrachromosomal clusters that seem to exhibit a closer proximity in space than on their chromosomal DNA sequence. We further discovered interchromosomal gene clusters that contain genes from different chromosomes within the human genome, but are located on a single chromosome in mouse. By identifying δ-teams with families, we provide a flexible model to discover gene cluster candidates in Hi-C data. Our analysis of Hi-C data from human and mouse reveals several known gene clusters (thus validating our approach), but also few sparsely studied or possibly unknown gene cluster candidates that could be the source of further experimental investigations.

  15. Readers of Largest U.S. History Textbooks Discover a Storehouse of Misinformation.

    ERIC Educational Resources Information Center

    Putka, Gary

    1992-01-01

    Reports that a Texas advocacy group discovered thousands of errors in U.S. history textbooks. Notes that the books underwent the review after drawing favorable reactions from Texas education officials. Identifies possible explanations for the errors and steps being taken to reduce errors in the future. (SG)

  16. Using Appreciative Inquiry to Discover and Deliver Change for Surgical Technology Students

    ERIC Educational Resources Information Center

    Cabai, Katherine A.

    2012-01-01

    The purpose of this study was to examine efficacious teaching-learning strategies that community college stakeholders employ that enhance surgical technology student outcomes. Knowles's adult learning theory, constructivist theory, and appreciative inquiry served as the theoretical foundation for this study. Discovering effective aspects and…

  17. Rare high-impact disease variants: properties and identifications.

    PubMed

    Park, Leeyoung; Kim, Ju Han

    2016-03-21

    Although many genome-wide association studies have been performed, the identification of disease polymorphisms remains important. It is now suspected that many rare disease variants induce the association signal of common variants in linkage disequilibrium (LD). Based on recent development of genetic models, the current study provides explanations of the existence of rare variants with high impacts and common variants with low impacts. Disease variants are neither necessary nor sufficient due to gene-gene or gene-environment interactions. A new method was developed based on theoretical aspects to identify both rare and common disease variants by their genotypes. Common disease variants were identified with relatively small odds ratios and relatively small sample sizes, except for specific situations in which the disease variants were in strong LD with a variant with a higher frequency. Rare disease variants with small impacts were difficult to identify without increasing sample sizes; however, the method was reasonably accurate for rare disease variants with high impacts. For rare variants, dominant variants generally showed better Type II error rates than recessive variants; however, the trend was reversed for common variants. Type II error rates increased in gene regions containing more than two disease variants because the more common variant, rather than both disease variants, was usually identified. The proposed method would be useful for identifying common disease variants with small impacts and rare disease variants with large impacts when disease variants have the same effects on disease presentation.

  18. Prospects for Ground-Based Detection and Follow-up of TESS-Discovered Exoplanets

    NASA Astrophysics Data System (ADS)

    Varakian, Matthew; Deming, Drake

    2018-01-01

    The Transiting Exoplanet Survey Satellite (TESS) will monitor over 200,000 main sequence dwarf stars for exoplanetary transits, with the goal of discovering small planets orbiting stars that are bright enough for follow-up observations. We here evaluate the prospects for ground-based transit detection and follow-up of the TESS-discovered planets. We focus particularly on the TESS planets that only transit once during each 27.4 day TESS observing window per region, and we calculate to what extent ground-based recovery of additional transits will be possible. Using simulated exoplanet systems from Sullivan et al. and assuming the use of a 60-cm telescope at a high quality observing site, we project the S/N ratios for transits of such planets. We use Phoenix stellar models for stars with surface temperatures from 2500K to 12000K, and we account for limb darkening, red atmospheric noise, and missed transits due to the day-night cycle and poor weather.

  19. Leveraging Collaborative Filtering to Accelerate Rare Disease Diagnosis

    PubMed Central

    Shen, Feichen; Liu, Sijia; Wang, Yanshan; Wang, Liwei; Afzal, Naveed; Liu, Hongfang

    2017-01-01

    In the USA, rare diseases are defined as those affecting fewer than 200,000 patients at any given time. Patients with rare diseases are frequently misdiagnosed or undiagnosed which may due to the lack of knowledge and experience of care providers. We hypothesize that patients’ phenotypic information available in electronic medical records (EMR) can be leveraged to accelerate disease diagnosis based on the intuition that providers need to document associated phenotypic information to support the diagnosis decision, especially for rare diseases. In this study, we proposed a collaborative filtering system enriched with natural language processing and semantic techniques to assist rare disease diagnosis based on phenotypic characterization. Specifically, we leveraged four similarity measurements with two neighborhood algorithms on 2010-2015 Mayo Clinic unstructured large patient cohort and evaluated different approaches. Preliminary results demonstrated that the use of collaborative filtering with phenotypic information is able to stratify patients with relatively similar rare diseases. PMID:29854225

  20. Leveraging Collaborative Filtering to Accelerate Rare Disease Diagnosis.

    PubMed

    Shen, Feichen; Liu, Sijia; Wang, Yanshan; Wang, Liwei; Afzal, Naveed; Liu, Hongfang

    2017-01-01

    In the USA, rare diseases are defined as those affecting fewer than 200,000 patients at any given time. Patients with rare diseases are frequently misdiagnosed or undiagnosed which may due to the lack of knowledge and experience of care providers. We hypothesize that patients' phenotypic information available in electronic medical records (EMR) can be leveraged to accelerate disease diagnosis based on the intuition that providers need to document associated phenotypic information to support the diagnosis decision, especially for rare diseases. In this study, we proposed a collaborative filtering system enriched with natural language processing and semantic techniques to assist rare disease diagnosis based on phenotypic characterization. Specifically, we leveraged four similarity measurements with two neighborhood algorithms on 2010-2015 Mayo Clinic unstructured large patient cohort and evaluated different approaches. Preliminary results demonstrated that the use of collaborative filtering with phenotypic information is able to stratify patients with relatively similar rare diseases.

  1. Ecology and exploration of the rare biosphere.

    PubMed

    Lynch, Michael D J; Neufeld, Josh D

    2015-04-01

    The profound influence of microorganisms on human life and global biogeochemical cycles underlines the value of studying the biogeography of microorganisms, exploring microbial genomes and expanding our understanding of most microbial species on Earth: that is, those present at low relative abundance. The detection and subsequent analysis of low-abundance microbial populations—the 'rare biosphere'—have demonstrated the persistence, population dynamics, dispersion and predation of these microbial species. We discuss the ecology of rare microbial populations, and highlight molecular and computational methods for targeting taxonomic 'blind spots' within the rare biosphere of complex microbial communities.

  2. Locally rare species influence grassland ecosystem multifunctionality.

    PubMed

    Soliveres, Santiago; Manning, Peter; Prati, Daniel; Gossner, Martin M; Alt, Fabian; Arndt, Hartmut; Baumgartner, Vanessa; Binkenstein, Julia; Birkhofer, Klaus; Blaser, Stefan; Blüthgen, Nico; Boch, Steffen; Böhm, Stefan; Börschig, Carmen; Buscot, Francois; Diekötter, Tim; Heinze, Johannes; Hölzel, Norbert; Jung, Kirsten; Klaus, Valentin H; Klein, Alexandra-Maria; Kleinebecker, Till; Klemmer, Sandra; Krauss, Jochen; Lange, Markus; Morris, E Kathryn; Müller, Jörg; Oelmann, Yvonne; Overmann, Jörg; Pašalić, Esther; Renner, Swen C; Rillig, Matthias C; Schaefer, H Martin; Schloter, Michael; Schmitt, Barbara; Schöning, Ingo; Schrumpf, Marion; Sikorski, Johannes; Socher, Stephanie A; Solly, Emily F; Sonnemann, Ilja; Sorkau, Elisabeth; Steckel, Juliane; Steffan-Dewenter, Ingolf; Stempfhuber, Barbara; Tschapka, Marco; Türke, Manfred; Venter, Paul; Weiner, Christiane N; Weisser, Wolfgang W; Werner, Michael; Westphal, Catrin; Wilcke, Wolfgang; Wolters, Volkmar; Wubet, Tesfaye; Wurst, Susanne; Fischer, Markus; Allan, Eric

    2016-05-19

    Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity-multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above- and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities. © 2016 The Author(s).

  3. Locally rare species influence grassland ecosystem multifunctionality

    PubMed Central

    Manning, Peter; Prati, Daniel; Gossner, Martin M.; Alt, Fabian; Arndt, Hartmut; Baumgartner, Vanessa; Binkenstein, Julia; Birkhofer, Klaus; Blaser, Stefan; Blüthgen, Nico; Boch, Steffen; Böhm, Stefan; Börschig, Carmen; Buscot, Francois; Diekötter, Tim; Heinze, Johannes; Hölzel, Norbert; Jung, Kirsten; Klaus, Valentin H.; Klein, Alexandra-Maria; Kleinebecker, Till; Klemmer, Sandra; Krauss, Jochen; Lange, Markus; Morris, E. Kathryn; Müller, Jörg; Oelmann, Yvonne; Overmann, Jörg; Pašalić, Esther; Renner, Swen C.; Rillig, Matthias C.; Schaefer, H. Martin; Schloter, Michael; Schmitt, Barbara; Schöning, Ingo; Schrumpf, Marion; Sikorski, Johannes; Socher, Stephanie A.; Solly, Emily F.; Sonnemann, Ilja; Sorkau, Elisabeth; Steckel, Juliane; Steffan-Dewenter, Ingolf; Stempfhuber, Barbara; Tschapka, Marco; Türke, Manfred; Venter, Paul; Weiner, Christiane N.; Weisser, Wolfgang W.; Werner, Michael; Westphal, Catrin; Wilcke, Wolfgang; Wolters, Volkmar; Wubet, Tesfaye; Wurst, Susanne; Fischer, Markus; Allan, Eric

    2016-01-01

    Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity–multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above- and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities. PMID:27114572

  4. Rare Species (RS)

    Treesearch

    Steve Sutherland

    2006-01-01

    The FIREMON Rare Species (RS) method is used to assess changes in uncommon, perennial plant species when other monitoring methods are not effective. This method monitors individual plants and statistically quantifies changes in plant survivorship, growth, and reproduction over time. Plants are spatially located using distance along and from a permanent baseline, and...

  5. Ciliates and the rare biosphere-community ecology and population dynamics.

    PubMed

    Weisse, Thomas

    2014-01-01

    Application of deep sequencing technologies to environmental samples and some detailed morphological studies suggest that there is a vast, yet unexplored rare ciliate biosphere, tentatively defined in terms of operational taxonomic units. However, very few studies complemented molecular and phylogenetic data with morphological and ecological descriptions of the species inventory. This is mainly because the sampling effort increases strongly with decreasing species abundance. In spite of this limited knowledge, it is clear that species that are rare under certain environmental conditions (temporal rare biosphere) may become abundant when the physical, chemical, and biological variables of their habitat change. Furthermore, some species may always be present in low numbers if their dispersal rates are exceedingly high (accidental rare biosphere). An intriguing question is whether there are some species that are always rare, i.e., in every suitable environment. This permanent rare biosphere is conceptually different from the temporal rare biosphere. This review characterizes typical aquatic habitats of the rare ciliate biosphere, portrays different scenarios under which some or even many species may be permanently rare (background fauna), and identifies some fundamental questions that need to be addressed to achieve a better understanding of the population dynamics of the rare ciliate biosphere. © 2014 The Authors The Journal of Eukaryotic Microbiology published by Wiley Periodicals, Inc. on behalf of International Society of Protistologists.

  6. Protocols for Teaching Students How to Search for, Discover, and Evaluate Innovations

    ERIC Educational Resources Information Center

    Norton, William I., Jr.; Hale, Dena H.

    2011-01-01

    The authors introduce and develop protocols to guide aspiring entrepreneurs' behaviors in searching for and discovering innovative ideas that may have commercial potential. Systematic search has emerged as a theory-based, prescriptive framework to guide innovative behavior. Grounded in Fiet's theory of search and discovery, this article provides…

  7. Preliminary study of microtektites first discovered in the central Pacific by China

    NASA Technical Reports Server (NTRS)

    Hanchang, P.; Shong, Y.; Xi, M.; Shijie, S.

    1984-01-01

    Electron probe analysis was used to determine the chemical composition of microtektites discovered in the Central Pacific. An X-ray energy spectrum analysis was made, and the surface microstructure was investigated. The found microtektites appear to be younger than the microtektites reported in the Asia Australia Strewn Field.

  8. Rare genetic variants and the risk of cancer.

    PubMed

    Bodmer, Walter; Tomlinson, Ian

    2010-06-01

    There are good reasons to expect that common genetic variants do not explain all of the inherited risk of the common cancers, not least of these being the relatively low proportion of familial relative risk that common cancer SNPs currently explain. One promising source of the unexplained risk is rare, low-penetrance genetic variants, a class that ranges from low-frequency polymorphisms (allele frequency < 5%) through subpolymorphic variants (frequency 0.1-1.0%) to very low frequency or 'private' variants with frequencies of 0.1% or less. Examples of rare cancer variants include breast cancer susceptibility loci CHEK2, BRIP1 and PALB2. There are considerable challenges associated with the discovery and testing of rare predisposition alleles, many of which are illustrated by the issues associated with variants of unknown significance in the Mendelian cancer predisposition genes. However, whilst cost constraints remain, the technological barriers to rare variant discovery and large-scale genotyping no longer exist. If each individual carries many disease-causing rare variants, the so-called missing heritability of cancer might largely be explained. Whether or not rare variants do end up filling the heritability gap, it is imperative to look for them along side common variants.

  9. Re-discovering Mendel: The Case of Carl Correns

    NASA Astrophysics Data System (ADS)

    Rheinberger, Hans-Jörg

    2015-01-01

    Carl Erich Correns (1864-1933) is remembered in the annals of science as one of the three botanists who re-discovered Mendel's laws. He can also, however, be regarded as one of the founding figures of classical genetics in Germany. Between 1894 and 1899 he carried out the crossing experiments with corn and peas that led to the re-statement of Gregor Mendel's (1822-1884) results. Between 1900 and 1910, he explored the complications of these laws, including the coupling of factors due to their chromosomal location and the inheritance of sex, in a great number of plant species. In later years Correns became interested in and experimented on phenomena of extra-nuclear inheritance.

  10. Micromagnetics of rare-earth efficient permanent magnets

    NASA Astrophysics Data System (ADS)

    Fischbacher, Johann; Kovacs, Alexander; Gusenbauer, Markus; Oezelt, Harald; Exl, Lukas; Bance, Simon; Schrefl, Thomas

    2018-05-01

    The development of permanent magnets containing less or no rare-earth elements is linked to profound knowledge of the coercivity mechanism. Prerequisites for a promising permanent magnet material are a high spontaneous magnetization and a sufficiently high magnetic anisotropy. In addition to the intrinsic magnetic properties the microstructure of the magnet plays a significant role in establishing coercivity. The influence of the microstructure on coercivity, remanence, and energy density product can be understood by using micromagnetic simulations. With advances in computer hardware and numerical methods, hysteresis curves of magnets can be computed quickly so that the simulations can readily provide guidance for the development of permanent magnets. The potential of rare-earth reduced and rare-earth free permanent magnets is investigated using micromagnetic simulations. The results show excellent hard magnetic properties can be achieved in grain boundary engineered NdFeB, rare-earth magnets with a ThMn12 structure, Co-based nano-wires, and L10-FeNi provided that the magnet’s microstructure is optimized.

  11. Antibacterial, Antifungal and Nematicidal Activities of Rare Earth Ions.

    PubMed

    Wakabayashi, Tokumitsu; Ymamoto, Ayumi; Kazaana, Akira; Nakano, Yuta; Nojiri, Yui; Kashiwazaki, Moeko

    2016-12-01

    Despite the name, rare earth elements are relatively abundant in soil. Therefore, these elements might interact with biosphere during the history of life. In this study, we have examined the effect of rare earth ions on the growth of bacteria, fungi and soil nematode. All rare earth ions, except radioactive promethium that we have not tested, showed antibacterial and antifungal activities comparable to that of copper ions, which is widely used as antibacterial metals in our daily life. Rare earth ions also have nematicidal activities as they strongly perturb the embryonic development of the nematode, Caenorhabditis elegans. Interestingly, the nematicidal activity increased with increasing atomic number of lanthanide ions. Since the rare earth ions did not show high toxicity to the human lymphoblastoid cell line or even stimulate the growth of the cultured cells at 1 mM, it raised the possibility that we can substitute rare earth elements for the antibacterial metals usually used because of their safety.

  12. Cost of illness and economic evaluation in rare diseases.

    PubMed

    López-Bastida, Julio; Oliva-Moreno, Juan

    2010-01-01

    Rare diseases are a major cause of morbidity and mortality in high income countries and have major repercussions on individuals and health care systems. This chapter examines the health economy of rare diseases from two different perspectives: firstly, the study of the economic impact of rare diseases (Cost of Illness studies); and, secondly, cost-effectiveness evaluation, which evaluates both the costs and results of the health care technologies applied in rare diseases. From the point of view of economics, health resource allocation is based on the principle of scarcity, as there are not - and never will be- sufficient resources for all worthy objectives. Hence, policy makers should balance costs and health outcomes. Rare diseases may well represent a significant societal burden that should rightly receive appropriate prioritisation of health care resources. As new and seemingly expensive health care technologies are developed for rare diseases, it will become increasingly important to evaluate potential and real impact of these new technologies in both dimensions: social costs and health outcomes.

  13. Dioctophymiasis: A Rare Case Report

    PubMed Central

    Kaval, Sunil; Tewari, Swati

    2016-01-01

    Dioctophyma renale commonly known as “giant kidney worm’ is found in the kidney of carnivorous mammals. Human infestation is rare, but results in destruction of the kidneys. Very few cases have been reported worldwide. We are here reporting a case of Dioctophymiasis in a 35-year-old male patient who presented with retention of urine and subsequent passage of worm and blood in urine. The worm was confirmed as Dioctophyma renale based on its morphology and clinical presentation. This is a very rare case report and to best of our knowledge only two cases have been reported from India. PMID:27042466

  14. Dioctophymiasis: A Rare Case Report.

    PubMed

    Chauhan, Sapna; Kaval, Sunil; Tewari, Swati

    2016-02-01

    Dioctophyma renale commonly known as "giant kidney worm' is found in the kidney of carnivorous mammals. Human infestation is rare, but results in destruction of the kidneys. Very few cases have been reported worldwide. We are here reporting a case of Dioctophymiasis in a 35-year-old male patient who presented with retention of urine and subsequent passage of worm and blood in urine. The worm was confirmed as Dioctophyma renale based on its morphology and clinical presentation. This is a very rare case report and to best of our knowledge only two cases have been reported from India.

  15. Tunable, rare earth-doped solid state lasers

    DOEpatents

    Emmett, John L.; Jacobs, Ralph R.; Krupke, William F.; Weber, Marvin J.

    1980-01-01

    Laser apparatus comprising combinations of an excimer pump laser and a rare earth-doped solid matrix, utilizing the 5d-4f radiative transition in a rare earth ion to produce visible and ultra-violet laser radiation with high overall efficiency in selected cases and relatively long radiative lifetimes.

  16. Health Systems Sustainability and Rare Diseases.

    PubMed

    Ferrelli, Rita Maria; De Santis, Marta; Egle Gentile, Amalia; Taruscio, Domenica

    2017-01-01

    The paper is addressing aspects of health system sustainability for rare diseases in relation to the current economic crisis and equity concerns. It takes into account the results of the narrative review carried out in the framework of the Joint Action for Rare Diseases (Joint RD-Action) "Promoting Implementation of Recommendations on Policy, Information and Data for Rare Diseases", that identified networks as key factors for health systems sustainability for rare diseases. The legal framework of European Reference Networks and their added value is also presented. Networks play a relevant role for health systems sustainability, since they are based upon, pay special attention to and can intervene on health systems knowledge development, partnership, organizational structure, resources, leadership and governance. Moreover, sustainability of health systems can not be separated from the analysis of the context and the action on it, including fiscal equity. As a result of the financial crisis of 2008, cuts of public health-care budgets jeopardized health equity, since the least wealthy suffered from the greatest health effects. Moreover, austerity policies affected economic growth much more adversely than previously believed. Therefore, reducing public health expenditure not only is going to jeopardise citizens' health, but also to hamper fair and sustainable development.

  17. Discover Earth: An earth system science program for libraries and their communities

    NASA Astrophysics Data System (ADS)

    Curtis, L.; Dusenbery, P.

    2010-12-01

    The view from space has deepened our understanding of Earth as a global, dynamic system. Instruments on satellites and spacecraft, coupled with advances in ground-based research, have provided us with astonishing new perspectives of our planet. Now more than ever, enhancing the public’s understanding of Earth’s physical and biological systems is vital to helping citizens make informed policy decisions especially when they are faced with the consequences of global climate change. In spite of this relevance, there are many obstacles to achieving broad public understanding of key earth system science (ESS) concepts. Strategies for addressing climate change can only succeed with the full engagement of the general public. As reported by U.S. News and World Report in 2010, small towns in rural America are emerging as the front line in the climate change debate in the country. The Space Science Institute’s National Center for Interactive Learning (NCIL) in partnership with the American Library Association (ALA), the Lunar and Planetary Institute (LPI), and the National Girls Collaborative Project (NGCP) have received funding from NSF to develop a national project called the STAR Library Education Network: a hands-on learning program for libraries and their communities (or STAR-Net for short). STAR stands for Science-Technology, Activities and Resources. There are two distinct components of STAR-Net: Discover Earth and Discover Tech. While the focus for education reform is on school improvement, there is considerable research that supports the role that out-of-school experiences can play in student achievement. Libraries provide an untapped resource for engaging underserved youth and their families in fostering an appreciation and deeper understanding of science and technology topics. The overarching goal of the project is to reach underserved youth and their families with informal STEM learning experiences. The Discover Earth part of STAR_Net will produce ESS

  18. NEWLY DISCOVERED PLANETS ORBITING HD 5319, HD 11506, HD 75784 AND HD 10442 FROM THE N2K CONSORTIUM

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

    Giguere, Matthew J.; Fischer, Debra A.; Brewer, John M.

    2015-01-20

    Initially designed to discover short-period planets, the N2K campaign has since evolved to discover new worlds at large separations from their host stars. Detecting such worlds will help determine the giant planet occurrence at semi-major axes beyond the ice line, where gas giants are thought to mostly form. Here we report four newly discovered gas giant planets (with minimum masses ranging from 0.4 to 2.1 M {sub Jup}) orbiting stars monitored as part of the Next 2000 target stars (N2K) Doppler Survey program. Two of these planets orbit stars already known to host planets: HD 5319 and HD 11506. Themore » remaining discoveries reside in previously unknown planetary systems: HD 10442 and HD 75784. The refined orbital period of the inner planet orbiting HD 5319 is 641 days. The newly discovered outer planet orbits in 886 days. The large masses combined with the proximity to a 4:3 mean motion resonance make this system a challenge to explain with current formation and migration theories. HD 11506 has one confirmed planet, and here we confirm a second. The outer planet has an orbital period of 1627.5 days, and the newly discovered inner planet orbits in 223.6 days. A planet has also been discovered orbiting HD 75784 with an orbital period of 341.7 days. There is evidence for a longer period signal; however, several more years of observations are needed to put tight constraints on the Keplerian parameters for the outer planet. Lastly, an additional planet has been detected orbiting HD 10442 with a period of 1043 days.« less

  19. Collaboration for rare disease drug discovery research.

    PubMed

    Litterman, Nadia K; Rhee, Michele; Swinney, David C; Ekins, Sean

    2014-01-01

    Rare disease research has reached a tipping point, with the confluence of scientific and technologic developments that if appropriately harnessed, could lead to key breakthroughs and treatments for this set of devastating disorders. Industry-wide trends have revealed that the traditional drug discovery research and development (R&D) model is no longer viable, and drug companies are evolving their approach. Rather than only pursue blockbuster therapeutics for heterogeneous, common diseases, drug companies have increasingly begun to shift their focus to rare diseases. In academia, advances in genetics analyses and disease mechanisms have allowed scientific understanding to mature, but the lack of funding and translational capability severely limits the rare disease research that leads to clinical trials. Simultaneously, there is a movement towards increased research collaboration, more data sharing, and heightened engagement and active involvement by patients, advocates, and foundations. The growth in networks and social networking tools presents an opportunity to help reach other patients but also find researchers and build collaborations. The growth of collaborative software that can enable researchers to share their data could also enable rare disease patients and foundations to manage their portfolio of funded projects for developing new therapeutics and suggest drug repurposing opportunities. Still there are many thousands of diseases without treatments and with only fragmented research efforts. We will describe some recent progress in several rare diseases used as examples and propose how collaborations could be facilitated. We propose that the development of a center of excellence that integrates and shares informatics resources for rare diseases sponsored by all of the stakeholders would help foster these initiatives.

  20. Collaboration for rare disease drug discovery research

    PubMed Central

    Litterman, Nadia K.; Rhee, Michele; Swinney, David C.; Ekins, Sean

    2014-01-01

    Rare disease research has reached a tipping point, with the confluence of scientific and technologic developments that if appropriately harnessed, could lead to key breakthroughs and treatments for this set of devastating disorders. Industry-wide trends have revealed that the traditional drug discovery research and development (R&D) model is no longer viable, and drug companies are evolving their approach. Rather than only pursue blockbuster therapeutics for heterogeneous, common diseases, drug companies have increasingly begun to shift their focus to rare diseases. In academia, advances in genetics analyses and disease mechanisms have allowed scientific understanding to mature, but the lack of funding and translational capability severely limits the rare disease research that leads to clinical trials. Simultaneously, there is a movement towards increased research collaboration, more data sharing, and heightened engagement and active involvement by patients, advocates, and foundations. The growth in networks and social networking tools presents an opportunity to help reach other patients but also find researchers and build collaborations. The growth of collaborative software that can enable researchers to share their data could also enable rare disease patients and foundations to manage their portfolio of funded projects for developing new therapeutics and suggest drug repurposing opportunities. Still there are many thousands of diseases without treatments and with only fragmented research efforts. We will describe some recent progress in several rare diseases used as examples and propose how collaborations could be facilitated. We propose that the development of a center of excellence that integrates and shares informatics resources for rare diseases sponsored by all of the stakeholders would help foster these initiatives. PMID:25685324

  1. Host specificity and the probability of discovering species of helminth parasites.

    PubMed

    Poulin, R; Mouillot, D

    2005-06-01

    Different animal species have different probabilities of being discovered and described by scientists, and these probabilities are determined to a large extent by the biological characteristics of these species. For instance, species with broader geographical ranges are more likely to be encountered by collectors than species with restricted distributions; indeed, the size of the geographical range is often the best predictor of a species' date of description. For parasitic organisms, host specificity may be similarly linked to the probability of a species being found. Here, using data on 170 helminth species parasitic in freshwater fishes, we show that host specificity is associated with the year in which the helminths were described. Helminths that exploit more host species, and to a lesser degree those that exploit a broader taxonomic range of host species, tend to be discovered earlier than the more host-specific helminths. This pattern was observed across all helminth species, as well as within the different helminth taxa (trematodes, cestodes, nematodes and acanthocephalans). Our results demonstrate that the parasite species known at any given point in time are not a random subset of existing species, but rather a biased subset with respect to the parasites' biological properties.

  2. Readership Assessment of Missouri's "Discover&Enlighten": Implications for Publications and Teaching Programs.

    ERIC Educational Resources Information Center

    Wood-Turley, Sharon; Tucker, Mark

    2003-01-01

    Results of study to measure the effectiveness of Discover&Enlighten, a newsletter of the University of Missouri's College of Agriculture, Food and Natural Resources, indicate that respondents (n=150) desire a mix of stories, have a positive perception of the newsletter, and consider it to be truthful. (Contains 17 references.) (JOW)

  3. Discovering, Supporting, and Promoting Young Children's Passions and Interests: One Teacher's Reflections.

    ERIC Educational Resources Information Center

    Ferguson, Christine

    2001-01-01

    Describes the journey of one kindergarten teacher as she discovered, supported, and promoted the passions and interests of an at-risk kindergarten student, and shared in his joys of learning. Details an inquiry project about snakes, initiated by the student's knowledge about snakes, involving field trips, class discussion, learning centers, and…

  4. Separation Anxiety: An in-Class Game Designed to Help Students Discover Chromatography

    ERIC Educational Resources Information Center

    Samide, Michael J.

    2008-01-01

    An in-class activity has been developed to assist students in discovering chromatographic separations. Designed on the basis of plate theory, the game has students use instructor-provided partition coefficients to establish equilibrium for two different items between a stationary and mobile phase. As students work through equilibration and mobile…

  5. Rare cancers in The Netherlands: a population-based study.

    PubMed

    van der Zwan, Jan M; van Dijk, Boukje A C; Visser, Otto; van Krieken, Han J H J M; Capocaccia, Riccardo; Siesling, Sabine

    2018-07-01

    The conventional definition for rare disease is based on prevalence. Because of differences in prognosis, a definition on the basis of incidence was deemed to be more appropriate for rare cancers. Within the European RARECARE project, a definition was introduced that defines cancers as rare when the crude incidence rate is less than six per 100 000 per year. In this study, we applied the RARECARE definition for rare cancer to the Netherlands; this to identify the usefulness of the definition in a single country and to provide more insight into the burden of rare cancers in the Netherlands. Data for 2004 through 2008 were extracted from the Netherlands Cancer Registry and classified according to the RARECARE entities (tumour groupings). Crude and European standardized incidence rates were calculated. Out of the 260 entities, 223 (86%) were rare according to the definition, accounting for 14 000 cancers (17% of all). Considerable fluctuations in crude rates over years were observed for the major group of cancers. Rare tumours in the Netherlands constituted 17% of all newly diagnosed tumours, but were divided over 223 different entities, indicating the challenge that faces clinicians. To make the definition of rare cancers better applicable, it should be refined by taking into consideration the sex-specific incidence for sex-specific cancer sites. Moreover, a mean incidence over 5 years will provide more solid insight into the burden, eliminating large fluctuations in time of most of the cancers.

  6. Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the "-Omics" Era.

    PubMed

    Stamou, M I; Cox, K H; Crowley, William F

    2015-12-01

    The neuroendocrine regulation of reproduction is an intricate process requiring the exquisite coordination of an assortment of cellular networks, all converging on the GnRH neurons. These neurons have a complex life history, migrating mainly from the olfactory placode into the hypothalamus, where GnRH is secreted and acts as the master regulator of the hypothalamic-pituitary-gonadal axis. Much of what we know about the biology of the GnRH neurons has been aided by discoveries made using the human disease model of isolated GnRH deficiency (IGD), a family of rare Mendelian disorders that share a common failure of secretion and/or action of GnRH causing hypogonadotropic hypogonadism. Over the last 30 years, research groups around the world have been investigating the genetic basis of IGD using different strategies based on complex cases that harbor structural abnormalities or single pleiotropic genes, endogamous pedigrees, candidate gene approaches as well as pathway gene analyses. Although such traditional approaches, based on well-validated tools, have been critical to establish the field, new strategies, such as next-generation sequencing, are now providing speed and robustness, but also revealing a surprising number of variants in known IGD genes in both patients and healthy controls. Thus, before the field moves forward with new genetic tools and continues discovery efforts, we must reassess what we know about IGD genetics and prepare to hold our work to a different standard. The purpose of this review is to: 1) look back at the strategies used to discover the "known" genes implicated in the rare forms of IGD; 2) examine the strengths and weaknesses of the methodologies used to validate genetic variation; 3) substantiate the role of known genes in the pathophysiology of the disease; and 4) project forward as we embark upon a widening use of these new and powerful technologies for gene discovery.

  7. Rare Earth Doped High Temperature Ceramic Selective Emitters

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L.; Pal, AnnaMarie; Patton, Martin O.; Jenkins, Phillip P.

    1999-01-01

    As a result of their electron structure, rare earth ions in crystals at high temperature emit radiation in several narrow bands rather than in a continuous blackbody manner. This study develops a spectral emittance model for films of rare earth containing materials. Although there are several possible rare earth doped high temperature materials, this study was confined to rare earth aluminum garnets. Good agreement between experimental and theoretical spectral emittances was found for erbium, thulium and erbium-holmium aluminum garnets. Spectral emittances of these films are sensitive to temperature differences across the film. Emitter efficiency is also a sensitive function of temperature. For thulium aluminum garnet the efficiency is 0.38 at 1700 K but only 0.19 at 1262 K.

  8. SALICYLATE PROCESS FOR THORIUM SEPARATION FROM RARE EARTHS

    DOEpatents

    Cowan, G.A.

    1959-08-25

    The separation of thorium from rare earths is accomplished by forming an aqueous solution of salts of thorium and rare earths and sufficient acetate buffer to provide a pH of between 2 and 5, adding an ammonium salicylate to the aqueous buffered solution, contacting the resultant solution with a substantially water-immiscible organic solvent mixture of an ether and an ester, and separating the solvent extract phase containing thorium salicylate from the aqueous phase containing the rare earths.

  9. Chemical Abundance Measurements of Ultra-Faint Dwarf Galaxies Discovered by the Dark Energy Survey

    NASA Astrophysics Data System (ADS)

    Nagasawa, Daniel; Marshall, Jennifer L.; Simon, Joshua D.; Hansen, Terese; Li, Ting; Bernstein, Rebecca; Balbinot, Eduardo; Drlica-Wagner, Alex; Pace, Andrew; Strigari, Louis; Pellegrino, Craig; DePoy, Darren L.; Suntzeff, Nicholas; Bechtol, Keith; Dark Energy Suvey

    2018-01-01

    We present chemical abundance analysis results derived from high-resolution spectroscopy of ultra-faint dwarfs discovered by the Dark Energy Survey. Ultra-faint dwarf galaxies preserve a fossil record of the chemical abundance patterns imprinted by the first stars in the Universe. High-resolution spectroscopic observations of member stars in several recently discovered Milky Way satellites reveal a range of abundance patterns among ultra-faint dwarfs suggesting that star formation processes in the early Universe were quite diverse. The chemical content provides a glimpse not only of the varied nucleosynthetic processes and chemical history of the dwarfs themselves, but also the environment in which they were formed. We present the chemical abundance analysis of these objects and discuss possible explanations for the observed abundance patterns.

  10. Learning a Taxonomy of Predefined and Discovered Activity Patterns

    PubMed Central

    Krishnan, Narayanan; Cook, Diane J.; Wemlinger, Zachary

    2013-01-01

    Many intelligent systems that focus on the needs of a human require information about the activities that are being performed by the human. At the core of this capability is activity recognition. Activity recognition techniques have become robust but rarely scale to handle more than a few activities. They also rarely learn from more than one smart home data set because of inherent differences between labeling techniques. In this paper we investigate a data-driven approach to creating an activity taxonomy from sensor data found in disparate smart home datasets. We investigate how the resulting taxonomy can help analyze the relationship between classes of activities. We also analyze how the taxonomy can be used to scale activity recognition to a large number of activity classes and training datasets. We describe our approach and evaluate it on 34 smart home datasets. The results of the evaluation indicate that the hierarchical modeling can reduce training time while maintaining accuracy of the learned model. PMID:25302084

  11. Rare earth elements and permanent magnets (invited)

    NASA Astrophysics Data System (ADS)

    Dent, Peter C.

    2012-04-01

    Rare earth (RE) magnets have become virtually indispensible in a wide variety of industries such as aerospace, automotive, electronics, medical, and military. RE elements are essential ingredients in these high performance magnets based on intermetallic compounds RECo5, RE2TM17 (TM: transition metal), and RE2TM14B. Rare earth magnets are known for their superior magnetic properties—high induction, and coercive force. These properties arise due to the extremely high magnetocrystalline anisotropy made possible by unique 3d-4f interactions between transition metals and rare earths. For more than 40 years, these magnets remain the number one choice in applications that require high magnetic fields in extreme operating conditions—high demagnetization forces and high temperature. EEC produces and specializes in RECo5 and RE2TM17 type sintered magnets. Samarium and gadolinium are key RE ingredients in the powder metallurgical magnet production processes which include melting, crushing, jet milling, pressing, sintering, and heat treating. The magnetic properties and applications of these magnets will be discussed. We will also briefly discuss the past, current, and future of the permanent magnet business. Currently, over 95% of all pure rare earth oxides are sourced from China, which currently controls the market. We will provide insights regarding current and potential new magnet technologies and designer choices, which may mitigate rare earth supply chain issues now and into the future.

  12. Webinar Presentation: Using Metabolomics with Neonatal Blood Spots to Discover Causes of Childhood Leukemia

    EPA Pesticide Factsheets

    This presentation, Using Metabolomics with Neonatal Blood Spots to Discover Causes of Childhood Leukemia, was given at the NIEHS/EPA Children's Centers 2016 Webinar Series: Exposome held on May 11, 2016.

  13. The burden of rare cancers in the United States.

    PubMed

    DeSantis, Carol E; Kramer, Joan L; Jemal, Ahmedin

    2017-07-08

    There are limited published data on the burden of rare cancers in the United States. By using data from the North American Association of Central Cancer Registries and the Surveillance, Epidemiology, and End Results program, the authors provide information on incidence rates, stage at diagnosis, and survival for more than 100 rare cancers (defined as an incidence of fewer than 6 cases per 100,000 individuals per year) in the United States. Overall, approximately 20% of patients with cancer in the United States are diagnosed with a rare cancer. Rare cancers make up a larger proportion of cancers diagnosed in Hispanic (24%) and Asian/Pacific Islander (22%) patients compared with non-Hispanic blacks (20%) and non-Hispanic whites (19%). More than two-thirds (71%) of cancers occurring in children and adolescents are rare cancers compared with less than 20% of cancers diagnosed in patients aged 65 years and older. Among solid tumors, 59% of rare cancers are diagnosed at regional or distant stages compared with 45% of common cancers. In part because of this stage distribution, 5-year relative survival is poorer for patients with a rare cancer compared with those diagnosed with a common cancer among both males (55% vs 75%) and females (60% vs 74%). However, 5-year relative survival is substantially higher for children and adolescents diagnosed with a rare cancer (82%) than for adults (46% for ages 65-79 years). Continued efforts are needed to develop interventions for prevention, early detection, and treatment to reduce the burden of rare cancers. Such discoveries can often advance knowledge for all cancers. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:261-272. © 2017 American Cancer Society. © 2017 American Cancer Society.

  14. [Hungarian national plan and strategy for rare diseases].

    PubMed

    Kosztolányi, György

    2014-03-02

    The rarity of low prevalence diseases and the lack of information, research, diagnosis, treatment and expert availability may mean that the people affected do not benefit from the health resources and services they need. Rare diseases are considered to have little impact on society as a whole, yet they pose serious difficulties for sufferers and their families. By the end of the last century, two robust achievements in science and technology, i.e. the biotechnological and informatics revolutions, have created a real base for global approach to rare diseases by coordinating the capacities for health care, biomedical research and drug development and pooling the very limited resources available both nationally and transnationally. The European Commission has taken a number of actions which help patients and professionals to share expertise and information across borders with the objective of reducing the number of people suffering from these types of diseases. These actions together form the legal basis of the European Union policy on rare diseases. Orphan or rare diseases are now one of the priorities in the public health programmes in European Union. In 2009, the document "European Union Council Recommendation on an action in the field of rare diseases" was released with the main goal to provide national health authorities with supporting tools for the development and implementation of national plans and strategies for rare diseases by the end of 2013. This recommendation adopted by European Union Member States, allows common policy guidelines to be shared everywhere in Europe. By September 2013 the Hungarian National Plan for Rare Diseases, a health policy strategy until 2020 was finalized. The present report gives a short view on the document.

  15. Miscellaneous rare paratesticular tumors.

    PubMed

    Henley, J D; Ferry, J; Ulbright, T M

    2000-11-01

    A few uncommon but distinctive tumors may preferentially involve the paratestis. The 3 unusual tumors that represent the focus of this discussion are the ovarian-type epithelial tumors (OTET), the desmoplastic small round cell tumor (DSRCT), and the melanotic neuroectodermal tumor of infancy (MNTI). The OTETs are testicular homologues of their more common namesake counterparts that arise in the ovary. Most frequent of these are serous tumors of borderline malignancy, with fewer cases of serous carcinomas or other forms of mullerian differentiation. DSRCT is an increasingly recognized, aggressive, "small blue cell" neoplasm with distinctive clinical and pathologic features. These polyphenotypic tumors characteristically, but not invariably, arise in intimate association with the serosal membrane of the peritoneal cavity and harbor a signature translocation-t(11;22)(p13,q12). In the paratestis they often involve the surface of the epididymis. The MNTI is an enigmatic, histologically distinctive, low-grade neoplasm occasionally encountered in the epididymis. Recognition of its features is essential to avoid misdiagnosis as a more aggressive "small blue cell" neoplasm and consequent therapeutic mismanagement. Primary hematopoietic tumors of the paratesticular structures are rare. There appears to be a tendency for young men to have low-grade lymphomas with an indolent course and older patients to develop higher-grade tumors. Plasmacytoma and granulocytic sarcoma of the paratestis are even more rare and are often susceptible to misinterpretation. Finally, metastatic tumors and a variety of other very rare neoplasms are discussed.

  16. Development of Creativity: The Influence of Varying Levels of Implementation of the DISCOVER Curriculum Model, a Non-Traditional Pedagogical Approach

    ERIC Educational Resources Information Center

    Maker, C. June; Jo, Sonmi; Muammar, Omar M.

    2008-01-01

    Development of creativity is influenced by multiple factors, including the environment, developmental changes, and measurement tools. In this study, we investigated the relationship between creativity development and implementation of the Discovering Intellectual Strengths and Capabilities while Observing Varied Ethnic Responses (DISCOVER)…

  17. Use of the Culture Care Theory and ethnonursing method to discover how nursing faculty teach culture care.

    PubMed

    Mixer, Sandra J

    2008-04-01

    As the world becomes increasingly multicultural, transcultural nursing education is critical to ensuring a culturally competent workforce. This paper presents a comprehensive review of literature and results of an ethnonursing pilot study using the Culture Care Theory (CCT) to discover how nursing faculty teach culture care. The literature revealed that despite 50 years of transcultural nursing knowledge development through theory, research and practice, there remains a lack of formal, integrated culture education in nursing. The importance of faculty providing generic and professional care to nursing students and using an organising framework to teach culture care was discovered. Additionally, care was essential for faculty health and well-being to enable faculty to teach culture care. This unique use of the theory and method demonstrates its usefulness in discovering and describing the complex nature of teaching culture care. Larger scale studies are predicted to further substantiate the CCT, building the discipline of nursing.

  18. Rhabdoid Meningioma of Brain - A Rare Aggressive Tumor

    PubMed Central

    Mondal, Sajeeb; Pradhan, Rajashree; Pal, Subrata; Chatterjee, Sharmistha; Bandyapadhyay, Arindam; Bhattacharyya, Debosmita

    2017-01-01

    Rhabdoid meningioma is a rare aggressive variant of meningioma, regarded as WHO Grade III type. Histologically and cytologically, it is distinctive type having abundant eosinophilic cytoplasm, cytoplasmic inclusion with eccentrically placed vesicular nuclei and prominent nucleoli. High recurrence rate and poor outcome are important features. Here, we are presenting a rare case of rhabdoid meningioma found in a recurrent meningioma of the posterior fossa in a middle-aged female. We emphasized the squash cytology and histology finding of the rare neoplasm. PMID:28900335

  19. eRAM: encyclopedia of rare disease annotations for precision medicine.

    PubMed

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

    2018-01-04

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

  20. The impact of rare variation on gene expression across tissues.

    PubMed

    Li, Xin; Kim, Yungil; Tsang, Emily K; Davis, Joe R; Damani, Farhan N; Chiang, Colby; Hess, Gaelen T; Zappala, Zachary; Strober, Benjamin J; Scott, Alexandra J; Li, Amy; Ganna, Andrea; Bassik, Michael C; Merker, Jason D; Hall, Ira M; Battle, Alexis; Montgomery, Stephen B

    2017-10-11

    Rare genetic variants are abundant in humans and are expected to contribute to individual disease risk. While genetic association studies have successfully identified common genetic variants associated with susceptibility, these studies are not practical for identifying rare variants. Efforts to distinguish pathogenic variants from benign rare variants have leveraged the genetic code to identify deleterious protein-coding alleles, but no analogous code exists for non-coding variants. Therefore, ascertaining which rare variants have phenotypic effects remains a major challenge. Rare non-coding variants have been associated with extreme gene expression in studies using single tissues, but their effects across tissues are unknown. Here we identify gene expression outliers, or individuals showing extreme expression levels for a particular gene, across 44 human tissues by using combined analyses of whole genomes and multi-tissue RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project v6p release. We find that 58% of underexpression and 28% of overexpression outliers have nearby conserved rare variants compared to 8% of non-outliers. Additionally, we developed RIVER (RNA-informed variant effect on regulation), a Bayesian statistical model that incorporates expression data to predict a regulatory effect for rare variants with higher accuracy than models using genomic annotations alone. Overall, we demonstrate that rare variants contribute to large gene expression changes across tissues and provide an integrative method for interpretation of rare variants in individual genomes.

  1. Effects of rare-earth co-doping on the local structure of rare-earth phosphate glasses using high and low energy X-ray diffraction.

    PubMed

    Cramer, Alisha J; Cole, Jacqueline M; FitzGerald, Vicky; Honkimaki, Veijo; Roberts, Mark A; Brennan, Tessa; Martin, Richard A; Saunders, George A; Newport, Robert J

    2013-06-14

    Rare-earth co-doping in inorganic materials has a long-held tradition of facilitating highly desirable optoelectronic properties for their application to the laser industry. This study concentrates specifically on rare-earth phosphate glasses, (R2O3)x(R'2O3)y(P2O5)(1-(x+y)), where (R, R') denotes (Ce, Er) or (La, Nd) co-doping and the total rare-earth composition corresponds to a range between metaphosphate, RP3O9, and ultraphosphate, RP5O14. Thereupon, the effects of rare-earth co-doping on the local structure are assessed at the atomic level. Pair-distribution function analysis of high-energy X-ray diffraction data (Q(max) = 28 Å(-1)) is employed to make this assessment. Results reveal a stark structural invariance to rare-earth co-doping which bears testament to the open-framework and rigid nature of these glasses. A range of desirable attributes of these glasses unfold from this finding; in particular, a structural simplicity that will enable facile molecular engineering of rare-earth phosphate glasses with 'dial-up' lasing properties. When considered together with other factors, this finding also demonstrates additional prospects for these co-doped rare-earth phosphate glasses in nuclear waste storage applications. This study also reveals, for the first time, the ability to distinguish between P-O and P[double bond, length as m-dash]O bonding in these rare-earth phosphate glasses from X-ray diffraction data in a fully quantitative manner. Complementary analysis of high-energy X-ray diffraction data on single rare-earth phosphate glasses of similar rare-earth composition to the co-doped materials is also presented in this context. In a technical sense, all high-energy X-ray diffraction data on these glasses are compared with analogous low-energy diffraction data; their salient differences reveal distinct advantages of high-energy X-ray diffraction data for the study of amorphous materials.

  2. Discovering chemistry with an ab initio nanoreactor

    DOE PAGES

    Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert; ...

    2014-11-02

    Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provides detailed physical insight. While theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor – a highly accelerated, first-principles molecular dynamics simulation of chemical reactions that discovers new molecules and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor we show new pathways for glycine synthesis frommore » primitive compounds proposed to exist on the early Earth, providing new insight into the classic Urey-Miller experiment. Ultimately, these results highlight the emergence of theoretical and computational chemistry as a tool for discovery in addition to its traditional role of interpreting experimental findings.« less

  3. Discovering chemistry with an ab initio nanoreactor

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

    Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert

    Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provides detailed physical insight. While theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor – a highly accelerated, first-principles molecular dynamics simulation of chemical reactions that discovers new molecules and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor we show new pathways for glycine synthesis frommore » primitive compounds proposed to exist on the early Earth, providing new insight into the classic Urey-Miller experiment. Ultimately, these results highlight the emergence of theoretical and computational chemistry as a tool for discovery in addition to its traditional role of interpreting experimental findings.« less

  4. METHOD OF SEPARATING RARE EARTHS BY ION EXCHANGE

    DOEpatents

    Spedding, F.H.; Powell, J.E.

    1960-10-18

    A process is given for separating yttrium and rare earth values having atomic numbers of from 57 through 60 and 68 through 71 from an aqueous solution whose pH value can range from 1 to 9. All rare earths and yttrium are first adsorbed on a cation exchange resin, and they are then eluted with a solution of N-hydroxyethylethylenediaminetriacetic acid (HEDTA) in the order of decreasing atomic number, yttrium behaving like element 61; the effluents are collected in fractions. The HEDTA is recovered by elution with ammonia solution and the resin is regenerated with sulfuric acid. Rare earths are precipitated from the various effluents with oxalic acid, and each supernatant is passed over cation exchange resin for adsorption of HEDTA and nonprecipitated rare earths: the oxalic acid is not retained by the resin.

  5. Non-union of the trapezium: rare consequence of a rare injury

    PubMed Central

    Samson, Deepak; Jones, Matthew; Mahon, Andrew

    2018-01-01

    Abstract Fractures of the trapezium are rare and easily missed. As these injuries are often imperceptible on plain radiographs, diagnosis in the ED setting is challenging. We report a case of an isolated fracture of the trapezium which was picked up as a non-union 5 months after the injury following persistence of symptoms. PMID:29765589

  6. On the Front Lines of Rare Disease Research

    MedlinePlus

    ... Diseases On the Front Lines of Rare Disease Research Past Issues / Spring 2016 Table of Contents Dr. ... MedlinePlus magazine. Many people may not hear about research on rare diseases. Why is this research important ...

  7. Rare earth elements in sedimentary phosphate deposits: Solution to the global REE crisis?

    USGS Publications Warehouse

    Emsbo, Poul; McLaughlin, Patrick I.; Breit, George N.; du Bray, Edward A.; Koenig, Alan E.

    2015-01-01

    The critical role of rare earth elements (REEs), particularly heavy REEs (HREEs), in high-tech industries has created a surge in demand that is quickly outstripping known global supply and has triggered a worldwide scramble to discover new sources. The chemical analysis of 23 sedimentary phosphate deposits (phosphorites) in the United States demonstrates that they are significantly enriched in REEs. Leaching experiments using dilute H2SO4 and HCl, extracted nearly 100% of their total REE content and show that the extraction of REEs from phosphorites is not subject to the many technological and environmental challenges that vex the exploitation of many identified REE deposits. Our data suggest that phosphate rock currently mined in the United States has the potential to produce a significant proportion of the world's REE demand as a byproduct. Importantly, the size and concentration of HREEs in some unmined phosphorites dwarf the world's richest REE deposits. Secular variation in phosphate REE contents identifies geologic time periods favorable for the formation of currently unrecognized high-REE phosphates. The extraordinary endowment, combined with the ease of REE extraction, indicates that such phosphorites might be considered as a primary source of REEs with the potential to resolve the global REE (particularly for HREE) supply shortage.

  8. Crystalline rare-earth activated oxyorthosilicate phosphor

    DOEpatents

    McClellan, Kenneth J.; Cooke, D. Wayne

    2004-02-10

    Crystalline, transparent, rare-earth activated lutetium oxyorthosilicate phosphor. The phosphor consists essentially of lutetium yttrium oxyorthosilicate activated with a rare-earth metal dopant M and having the general formula Lu(.sub.2-x-z)Y.sub.x M.sub.z SiO.sub.5, wherein 0.00.ltoreq.x.ltoreq.1.95, wherein 0.001.ltoreq.z.ltoreq.0.02, and wherein M is selected from Sm, Tb, Tm, Eu, Yb, and Pr. The phosphor also consists essentially of lutetium gadolinium oxyorthosilicate activated with a rare-earth metal dopant M and having the general formula Lu(.sub.2-x-z)Gd.sub.x M.sub.z SiO.sub.5, wherein 0.00.ltoreq.x.ltoreq.1.95, wherein 0.001.ltoreq.z.ltoreq.0.02, and wherein M is selected from Sm, Tb, Tm, Eu, Yb, and Pr. The phosphor also consists essentially of gadolinium yttrium oxyorthosilicate activated with a rare-earth metal dopant M and having the general formula Gd(.sub.2-x-z)Y.sub.x M.sub.z SiO.sub.5, wherein 0.00.ltoreq.x.ltoreq.1.95, wherein 0.001.ltoreq.z.ltoreq.0.02, and wherein M is selected from Sm, Tb, Tm, Eu, Yb, and Pr. The phosphor may be optically coupled to a photodetector to provide a radiation detector.

  9. Replacing critical rare earth materials in high energy density magnets

    NASA Astrophysics Data System (ADS)

    McCallum, R. William

    2012-02-01

    High energy density permanent magnets are crucial to the design of internal permanent magnet motors (IPM) for hybride and electric vehicles and direct drive wind generators. Current motor designs use rare earth permanent magnets which easily meet the performance goals, however, the rising concerns over cost and foreign control of the current supply of rare earth resources has motivated a search for non-rare earth based permanent magnets alloys with performance metrics which allow the design of permanent magnet motors and generators without rare earth magnets. This talk will discuss the state of non-rare-earth permanent magnets and efforts to both improve the current materials and find new materials. These efforts combine first principles calculations and meso-scale magnetic modeling with advance characterization and synthesis techniques in order to advance the state of the art in non rare earth permanent magnets. The use of genetic algorithms in first principle structural calculations, combinatorial synthesis in the experimental search for materials, atom probe microscopy to characterize grain boundaries on the atomic level, and other state of the art techniques will be discussed. In addition the possibility of replacing critical rare earth elements with the most abundant rare earth Ce will be discussed.

  10. DISCOVERY OF BRIGHT GALACTIC R CORONAE BOREALIS AND DY PERSEI VARIABLES: RARE GEMS MINED FROM ACVS

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

    Miller, A. A.; Richards, J. W.; Bloom, J. S.

    2012-08-20

    We present the results of a machine-learning (ML)-based search for new R Coronae Borealis (RCB) stars and DY Persei-like stars (DYPers) in the Galaxy using cataloged light curves from the All-Sky Automated Survey (ASAS) Catalog of Variable Stars (ACVS). RCB stars-a rare class of hydrogen-deficient carbon-rich supergiants-are of great interest owing to the insights they can provide on the late stages of stellar evolution. DYPers are possibly the low-temperature, low-luminosity analogs to the RCB phenomenon, though additional examples are needed to fully establish this connection. While RCB stars and DYPers are traditionally identified by epochs of extreme dimming that occurmore » without regularity, the ML search framework more fully captures the richness and diversity of their photometric behavior. We demonstrate that our ML method can use newly discovered RCB stars to identify additional candidates within the same data set. Our search yields 15 candidates that we consider likely RCB stars/DYPers: new spectroscopic observations confirm that four of these candidates are RCB stars and four are DYPers. Our discovery of four new DYPers increases the number of known Galactic DYPers from two to six; noteworthy is that one of the new DYPers has a measured parallax and is m Almost-Equal-To 7 mag, making it the brightest known DYPer to date. Future observations of these new DYPers should prove instrumental in establishing the RCB connection. We consider these results, derived from a machine-learned probabilistic classification catalog, as an important proof-of-concept for the efficient discovery of rare sources with time-domain surveys.« less

  11. A Phyletically Rare Gene Promotes the Niche-specific Fitness of an E. coli Pathogen during Bacteremia

    PubMed Central

    Wiles, Travis J.; Lewis, Adam J.; Mobley, Harry L. T.; Casjens, Sherwood R.; Mulvey, Matthew A.

    2013-01-01

    In bacteria, laterally acquired genes are often concentrated within chromosomal regions known as genomic islands. Using a recently developed zebrafish infection model, we set out to identify unique factors encoded within genomic islands that contribute to the fitness and virulence of a reference urosepsis isolate—extraintestinal pathogenic Escherichia coli strain CFT073. By screening a series of deletion mutants, we discovered a previously uncharacterized gene, neaT, that is conditionally required by the pathogen during systemic infections. In vitro assays indicate that neaT can limit bacterial interactions with host phagocytes and alter the aggregative properties of CFT073. The neaT gene is localized within an integrated P2-like bacteriophage in CFT073, but was rarely found within other proteobacterial genomes. Sequence-based analyses revealed that neaT homologues are present, but discordantly conserved, within a phyletically diverse set of bacterial species. In CFT073, neaT appears to be unameliorated, having an exceptionally A+T-rich composition along with a notably altered codon bias. These data suggest that neaT was recently brought into the proteobacterial pan-genome from an extra-phyletic source. Interestingly, even in G+C-poor genomes, as found within the Firmicutes lineage, neaT-like genes are often unameliorated. Sequence-level features of neaT homologues challenge the common supposition that the A+T-rich nature of many recently acquired genes reflects the nucleotide composition of their genomes of origin. In total, these findings highlight the complexity of the evolutionary forces that can affect the acquisition, utilization, and assimilation of rare genes that promote the niche-dependent fitness and virulence of a bacterial pathogen. PMID:23459509

  12. Material efficiency: rare and critical metals.

    PubMed

    Ayres, Robert U; Peiró, Laura Talens

    2013-03-13

    In the last few decades, progress in electronics, especially, has resulted in important new uses for a number of geologically rare metals, some of which were mere curiosities in the past. Most of them are not mined for their own sake (gold, the platinum group metals and the rare Earth elements are exceptions) but are found mainly in the ores of the major industrial metals, such as aluminium, copper, zinc and nickel. We call these major metals 'attractors' and the rare accompanying metals 'hitch-hikers'. The key implication is that rising prices do not necessarily call forth greater output because that would normally require greater output of the attractor metal. We trace the geological relationships and the functional uses of these metals. Some of these metals appear to be irreplaceable in the sense that there are no known substitutes for them in their current functional uses. Recycling is going to be increasingly important, notwithstanding a number of barriers.

  13. Rare earth phosphors and phosphor screens

    DOEpatents

    Buchanan, Robert A.; Maple, T. Grant; Sklensky, Alden F.

    1981-01-01

    This invention relates to rare earth phosphor screens for converting image carrying incident radiation to image carrying visible or near-visible radiation and to the rare earth phosphor materials utilized in such screens. The invention further relates to methods for converting image carrying charged particles to image carrying radiation principally in the blue and near-ultraviolet region of the spectrum and to stabilized rare earth phosphors characterized by having a continuous surface layer of the phosphors of the invention. More particularly, the phosphors of the invention are oxychlorides and oxybromides of yttrium, lanthanum and gadolinium activated with trivalent cerium and the conversion screens are of the type illustratively including x-ray conversion screens, image amplifier tube screens, neutron imaging screens, cathode ray tube screens, high energy gamma ray screens, scintillation detector screens and screens for real-time translation of image carrying high energy radiation to image carrying visible or near-visible radiation.

  14. A rare and cryptic endemic of the Central Rocky Mountains, U.S.A: The distribution of the Arapahoe snowfly, Arsapnia arapahoe (Nelson & Kondratieff, 1988) (Plecoptera: Capniidae)

    USGS Publications Warehouse

    Fairchild, Matthew P.; Belcher, Thomas P.; Zuellig, Robert E.; Vieira, Nicole K.M.; Kondratieff, Boris C.

    2017-01-01

    The Arapahoe snowfly, Arsapnia arapahoe (Nelson & Kondratieff, 1988) (Plecoptera: Capniidae) is a candidate species warranted for listing under the Endangered Species Act. Prior to this study, A. arapahoe was known from only two tributaries of the Cache la Poudre River in Larimer County, Colorado: Young Gulch and Elkhorn Creek. The objectives of this study were to determine the distribution of this endemic stonefly, and to identify sympatric species as possible surrogate indicators of its occurrence. Eighty-four streams were sampled within the expected geographical range and emergence time-period from 2013 to 2017. Adults of A. arapahoe were discovered in 19 first-, second-, and fourth-order streams beyond the original type localities tributary to the Cache la Poudre River. The new and recently recorded localities were discovered in the Big Thompson River, St. Vrain River, Boulder Creek, and Upper South Platte River Watersheds. Two species, A. decepta (Banks, 1897) and Capnia gracilaria Claassen, 1924, always co-occurred with A. arapahoe, suggesting this species pair may serve as a surrogate indicator of suitable stream habitat for A. arapahoe. Suggestions for future investigation into the distribution, life-history, and habitat of A. arapahoe are presented to aid the conservation of this rare and endemic Colorado stonefly.

  15. Rare gases in Samoan xenoliths

    NASA Astrophysics Data System (ADS)

    Poreda, R. J.; Farley, K. A.

    1992-09-01

    The rare gas isotopic compositions of residual harzburgite xenoliths from Savai'i (SAV locality) and an unnamed seamount south of the Samoan chain (PPT locality) provide important constraints on the rare gas evolution of the mantle and atmosphere. Despite heterogeneous trace element compositions, the rare gas characteristics of the xenoliths from each of the two localities are strikingly similar. SAV and PPT xenoliths have 3He/ 4He ratios of11.1 ± 0.5 R A and21.6 ± 1 R A, respectively; this range is comparable to the 3He/ 4He ratios in Samoan lavas and clearly demonstrates that they have trapped gases from a relatively undegassed reservoir. The neon results are not consistent with mixing between MORB and a plume source with an atmospheric signature. Rather, the neon isotopes reflect either a variably degassed mantle (with a relative order of degassing of Loihi < PPT < Reunion < SAV < MORB), or mixing between the Loihi source and MORB. The data supports the conclusions of Honda et al. that the 20Ne/ 22Ne ratio in the mantle more closely resembles the solar ratio than the atmospheric one. 40Ar/ 36Ar ratios in the least contaminated samples range from 4,000 to 12,000 with the highest values in the 22 RA PPT xenoliths. There is no evidence for atmospheric 40Ar/ 36Ar ratios in the mantle source of these samples, which indicates that the lower mantle may have 40Ar/ 36Ar ratios in excess of 5,000. Xenon isotopic anomalies in 129Xe and 136Xe are as high as 6%, or about half of the maximum MORB excess and are consistent with the less degassed nature of the Samoan mantle source. These results contradict previous suggestions that the high 3He/ 4He mantle has a near-atmospheric heavy rare gas isotopic composition.

  16. Rare itemsets mining algorithm based on RP-Tree and spark framework

    NASA Astrophysics Data System (ADS)

    Liu, Sainan; Pan, Haoan

    2018-05-01

    For the issues of the rare itemsets mining in big data, this paper proposed a rare itemsets mining algorithm based on RP-Tree and Spark framework. Firstly, it arranged the data vertically according to the transaction identifier, in order to solve the defects of scan the entire data set, the vertical datasets are divided into frequent vertical datasets and rare vertical datasets. Then, it adopted the RP-Tree algorithm to construct the frequent pattern tree that contains rare items and generate rare 1-itemsets. After that, it calculated the support of the itemsets by scanning the two vertical data sets, finally, it used the iterative process to generate rare itemsets. The experimental show that the algorithm can effectively excavate rare itemsets and have great superiority in execution time.

  17. Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the “-Omics” Era

    PubMed Central

    Stamou, M. I.; Cox, K. H.

    2015-01-01

    The neuroendocrine regulation of reproduction is an intricate process requiring the exquisite coordination of an assortment of cellular networks, all converging on the GnRH neurons. These neurons have a complex life history, migrating mainly from the olfactory placode into the hypothalamus, where GnRH is secreted and acts as the master regulator of the hypothalamic-pituitary-gonadal axis. Much of what we know about the biology of the GnRH neurons has been aided by discoveries made using the human disease model of isolated GnRH deficiency (IGD), a family of rare Mendelian disorders that share a common failure of secretion and/or action of GnRH causing hypogonadotropic hypogonadism. Over the last 30 years, research groups around the world have been investigating the genetic basis of IGD using different strategies based on complex cases that harbor structural abnormalities or single pleiotropic genes, endogamous pedigrees, candidate gene approaches as well as pathway gene analyses. Although such traditional approaches, based on well-validated tools, have been critical to establish the field, new strategies, such as next-generation sequencing, are now providing speed and robustness, but also revealing a surprising number of variants in known IGD genes in both patients and healthy controls. Thus, before the field moves forward with new genetic tools and continues discovery efforts, we must reassess what we know about IGD genetics and prepare to hold our work to a different standard. The purpose of this review is to: 1) look back at the strategies used to discover the “known” genes implicated in the rare forms of IGD; 2) examine the strengths and weaknesses of the methodologies used to validate genetic variation; 3) substantiate the role of known genes in the pathophysiology of the disease; and 4) project forward as we embark upon a widening use of these new and powerful technologies for gene discovery. PMID:26394276

  18. Marquette Island: A Distinct Mafic Lithology Discovered by Opportunity

    NASA Technical Reports Server (NTRS)

    Mittlefehldt, David W.; Gellert, R.; Herkenhoff, K. E.; Clark, B. C.; Cohen, B. A.; Fleischer, I.; Jolliff, B. L.; Klingelhoefer, G.; Ming, D. W.; Yingst, R. A.

    2010-01-01

    While rolling over the Meridiani Planum sedimentary terrane, the rover Opportunity has occasionally discovered large, > 10 cm erratics. Most of these have proven to be meteorites [1], but one - Bounce Rock - is a martian basaltic rock similar in composition to the meteorite EETA79001 lithology B [2]. Presently, Opportunity is intensively investigating an --30 cm tall rock named Marquette Island that may be a distinct type of martian mafic lithology. We report the results of its continuing investigation using the Microscopic Imager (MI); Mossbauer Spectrometer (MB) and Alpha Particle X-ray Spectrometer (APXS). A companion abstract discusses the results of Panoramic Camera (Pancam) imaging of the rock [3].

  19. Discovering New Light States at Neutrino Experiments

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

    Essig, Rouven; /SLAC; Harnik, Roni

    2011-08-11

    Experiments designed to measure neutrino oscillations also provide major opportunities for discovering very weakly coupled states. In order to produce neutrinos, experiments such as LSND collide thousands of Coulombs of protons into fixed targets, while MINOS and MiniBooNE also focus and then dump beams of muons. The neutrino detectors beyond these beam dumps are therefore an excellent arena in which to look for long-lived pseudoscalars or for vector bosons that kinetically mix with the photon. We show that these experiments have significant sensitivity beyond previous beam dumps, and are able to partially close the gap between laboratory experiments and supernovaemore » constraints on pseudoscalars. Future upgrades to the NuMI beamline and Project X will lead to even greater opportunities for discovery. We also discuss thin target experiments with muon beams, such as those available in COMPASS, and show that they constitute a powerful probe for leptophilic PNGBs.« less

  20. Discovering New Drugs on the Cellular Level

    NASA Technical Reports Server (NTRS)

    2005-01-01

    With the Vision for Space Exploration calling for a sustained human presence in space, astronauts will need to grow plants, while in orbit, for nourishment that they will not receive from only consuming dehydrated foods. As a potential source of food for long-duration missions, space-grown plants could also give astronauts an important psychological boost, as fresh vegetables could serve as a welcomed change from monotonous meals consisting of reconstituted foods in plastic bags. Even more, these plants could likely aid in the recycling of air and wastewater on spacecraft. With a helping hand from a company by the name of Biolog, Inc., NASA is studying the impacts of decreased gravity and spaceborne bacteria on the plants being grown for food in space. With a helping hand from NASA, this very same company is creating powerful new cell- and bacteria-analysis tools for use in discovering and developing new drugs on Earth.

  1. Mother Lode: The Untapped Rare Earth Mineral Resources of Vietnam

    DTIC Science & Technology

    2013-11-01

    Library of Congress, Congressional Research Service. Rare Earth Elements: The Global Supply Chain, 4. 14 Tse , Pui-Kwan. China’s Rare-Earth Industry...U.S. Geological Survey Open-File Report 2011–1042, 2. Figure 2. Global REO production, 1960-2011. Source: Tse , Pui-Kwan. China’s Rare-Earth...3 compiled from three sources: Tse , Pui-Kwan. China’s Rare-Earth Industry: U.S. Geological Survey Open-File Report 2011–1042, 4; Areddy, James T

  2. Rare earth niobate coordination polymers

    NASA Astrophysics Data System (ADS)

    Muniz, Collin N.; Patel, Hiral; Fast, Dylan B.; Rohwer, Lauren E. S.; Reinheimer, Eric W.; Dolgos, Michelle; Graham, Matt W.; Nyman, May

    2018-03-01

    Rare-earth (RE) coordination polymers are infinitely tailorable to yield luminescent materials for various applications. Here we described the synthesis of a heterometallic rare-earth coordination compound ((CH3)2SO)3(RE)NbO(C2O4)3((CH3)2SO) = dimethylsulfoxide, DMSO, (C2O2= oxalate), (RE=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb). The structure was obtained from single crystal X-ray diffraction of the La analogue. The Nb˭O and DMSO terminal-bonding character guides assembly of an open framework structure with noncentrosymmetric RE-coordination geometry, and large spacing between the RE centers. A second structure was observed by PXRD for the smaller rare earths (Dy, Ho, Er, Yb); this structure has not yet been determined. The materials were further characterized using FTIR, and photoluminescence measurements. Characteristic excitation and emission transitions were observed for RE = Nd, Sm, Eu, and Tb. Quantum yield (QY) measurements were performed by exciting Eu and Tb analoges at 394 nm (QY 66%) and 464 nm (QY 71%) for Eu; and 370 nm (QY=40%) for Tb. We attribute the high QY and bright luminescence to two main structure-function properties of the system; namely the absence of water in the structure, and absence of concentration quenching.

  3. Rare disease: a national survey of paediatricians' experiences and needs.

    PubMed

    Zurynski, Yvonne; Gonzalez, Aranzazu; Deverell, Marie; Phu, Amy; Leonard, Helen; Christodoulou, John; Elliott, Elizabeth

    2017-01-01

    To describe the experiences of Australian paediatricians while caring for children with rare diseases, and their educational and resource needs. A brief online survey was developed and deployed to a representative sample of 679 paediatricians from the Australian Paediatric Surveillance Unit database. Of the 679 paediatricians, 242 (36%) completed the survey. The respondents were representative of all states and territories of Australia, urban and rural regions, and hospital and private practice. Almost all respondents (93%) had seen children with one or more of >350 different rare diseases during their career; 74% had seen a new patient with rare disease in the last 6 months. The most common problems encountered while caring for patients were: diagnostic delays (65%), lack of available treatments (40%), clinical guidelines (36%) and uncertainty where to refer for peer support (35%). Few paediatricians said that rare diseases were adequately covered during university (40%) or the Fellowship of the Royal Australasian College of Physicians (50%) training, and 28% felt unprepared to care for patients with rare diseases. Paediatricians wanted lists of specialist referral services (82%) and online educational modules about rare diseases (78%) that could be accessed via one online portal that consolidated multiple resources. Smartphone applications on rare diseases were favoured by paediatricians aged <50 years and by female paediatricians. An online educational portal should be developed and maintained for accuracy and currency of information to support dissemination of rare disease guidelines, referral pathways and coordination services relevant to Australian paediatricians and other health professionals who care for children with rare diseases.

  4. Rare disease: a national survey of paediatricians’ experiences and needs

    PubMed Central

    Zurynski, Yvonne; Gonzalez, Aranzazu; Deverell, Marie; Phu, Amy; Leonard, Helen; Christodoulou, John; Elliott, Elizabeth

    2017-01-01

    Objective To describe the experiences of Australian paediatricians while caring for children with rare diseases, and their educational and resource needs. Design A brief online survey was developed and deployed to a representative sample of 679 paediatricians from the Australian Paediatric Surveillance Unit database. Results Of the 679 paediatricians, 242 (36%) completed the survey. The respondents were representative of all states and territories of Australia, urban and rural regions, and hospital and private practice. Almost all respondents (93%) had seen children with one or more of >350 different rare diseases during their career; 74% had seen a new patient with rare disease in the last 6 months. The most common problems encountered while caring for patients were: diagnostic delays (65%), lack of available treatments (40%), clinical guidelines (36%) and uncertainty where to refer for peer support (35%). Few paediatricians said that rare diseases were adequately covered during university (40%) or the Fellowship of the Royal Australasian College of Physicians (50%) training, and 28% felt unprepared to care for patients with rare diseases. Paediatricians wanted lists of specialist referral services (82%) and online educational modules about rare diseases (78%) that could be accessed via one online portal that consolidated multiple resources. Smartphone applications on rare diseases were favoured by paediatricians aged <50 years and by female paediatricians. Conclusions An online educational portal should be developed and maintained for accuracy and currency of information to support dissemination of rare disease guidelines, referral pathways and coordination services relevant to Australian paediatricians and other health professionals who care for children with rare diseases. PMID:29637168

  5. Innovative research methods for studying treatments for rare diseases: methodological review.

    PubMed

    Gagne, Joshua J; Thompson, Lauren; O'Keefe, Kelly; Kesselheim, Aaron S

    2014-11-24

    To examine methods for generating evidence on health outcomes in patients with rare diseases. Methodological review of existing literature. PubMed, Embase, and Academic Search Premier searched for articles describing innovative approaches to randomized trial design and analysis methods and methods for conducting observational research in patients with rare diseases. We assessed information related to the proposed methods, the specific rare disease being studied, and outcomes from the application of the methods. We summarize methods with respect to their advantages in studying health outcomes in rare diseases and provide examples of their application. We identified 46 articles that proposed or described methods for studying patient health outcomes in rare diseases. Articles covered a wide range of rare diseases and most (72%) were published in 2008 or later. We identified 16 research strategies for studying rare disease. Innovative clinical trial methods minimize sample size requirements (n=4) and maximize the proportion of patients who receive active treatment (n=2), strategies crucial to studying small populations of patients with limited treatment choices. No studies describing unique methods for conducting observational studies in patients with rare diseases were identified. Though numerous studies apply unique clinical trial designs and considerations to assess patient health outcomes in rare diseases, less attention has been paid to innovative methods for studying rare diseases using observational data. © Gagne et al 2014.

  6. PROCESS FOR SEPARATING AMERICIUM AND CURIUM FROM RARE EARTH ELEMENTS

    DOEpatents

    Baybarz, R.D.; Lloyd, M.H.

    1963-02-26

    This invention relates to methods of separating americium and curium values from rare earth values. In accordance with the invention americium, curium, and rare earth values are sorbed on an anion exchange resin. A major portion of the rare earth values are selectively stripped from the resin with a concentrated aqueous solution of lithium chloride, and americium, curium, and a minor portion of rare earth values are then stripped from the resin with a dilute aqueous solution of lithium chloride. The americium and curium values are further purified by increasing the concentration of lithium chloride in the solution to at least 8 molar and selectively extracting rare earth values from the resulting solution with a monoalkylphosphoric acid. (AEC)

  7. Adapting Knowledge Translation Strategies for Rare Rheumatic Diseases.

    PubMed

    Cellucci, Tania; Lee, Shirley; Webster, Fiona

    2016-08-01

    Rare rheumatic diseases present unique challenges to knowledge translation (KT) researchers. There is often an urgent need to transfer knowledge from research findings into clinical practice to facilitate earlier diagnosis and better outcomes. However, existing KT frameworks have not addressed the specific considerations surrounding rare diseases for which gold standard evidence is not available. Several widely adopted models provide guidance for processes and problems associated with KT. However, they do not address issues surrounding creation or synthesis of knowledge for rare diseases. Additional problems relate to lack of awareness or experience in intended knowledge users, low motivation, and potential barriers to changing practice or policy. Strategies to address the challenges of KT for rare rheumatic diseases include considering different levels of evidence available, linking knowledge creation and transfer directly, incorporating patient and physician advocacy efforts to generate awareness of conditions, and selecting strategies to address barriers to practice or policy change.

  8. Evidence for an active rare biosphere within freshwater protists community.

    PubMed

    Debroas, Didier; Hugoni, Mylène; Domaizon, Isabelle

    2015-03-01

    Studies on the active rare biosphere at the RNA level are mainly focused on Bacteria and Archaea and fail to include the protists, which are involved in the main biogeochemical cycles of the earth. In this study, the richness, composition and activity of the rare protistan biosphere were determined from a temporal survey of two lakes by pyrosequencing. In these ecosystems, the always rare OTUs represented 77.2% of the total OTUs and 76.6% of the phylogenetic diversity. From the various phylogenetic indices computed, the phylogenetic units (PUs) constituted exclusively by always rare OTUs were discriminated from the other PUs. Therefore, the rare biosphere included mainly taxa that are distant from the reference databases compared to the dominant ones. In addition, the rarest OTUs represented 59.8% of the active biosphere depicted by rRNA and the activity (rRNA:rDNA ratio) increased with the rarity. The high rRNA:rDNA ratio determined in the rare fraction highlights that some protists were active at low abundances and contribute to ecosystem functioning. Interestingly, the always rare and active OTUs were characterized by seasonal changes in relation with the main environmental parameters measured. In conclusion, the rare eukaryotes represent an active, dynamic and overlooked fraction in the lacustrine ecosystems. © 2015 John Wiley & Sons Ltd.

  9. Rare Cell Capture in Microfluidic Devices

    PubMed Central

    Pratt, Erica D.; Huang, Chao; Hawkins, Benjamin G.; Gleghorn, Jason P.; Kirby, Brian J.

    2010-01-01

    This article reviews existing methods for the isolation, fractionation, or capture of rare cells in microfluidic devices. Rare cell capture devices face the challenge of maintaining the efficiency standard of traditional bulk separation methods such as flow cytometers and immunomagnetic separators while requiring very high purity of the target cell population, which is typically already at very low starting concentrations. Two major classifications of rare cell capture approaches are covered: (1) non-electrokinetic methods (e.g., immobilization via antibody or aptamer chemistry, size-based sorting, and sheath flow and streamline sorting) are discussed for applications using blood cells, cancer cells, and other mammalian cells, and (2) electrokinetic (primarily dielectrophoretic) methods using both electrode-based and insulative geometries are presented with a view towards pathogen detection, blood fractionation, and cancer cell isolation. The included methods were evaluated based on performance criteria including cell type modeled and used, number of steps/stages, cell viability, and enrichment, efficiency, and/or purity. Major areas for improvement are increasing viability and capture efficiency/purity of directly processed biological samples, as a majority of current studies only process spiked cell lines or pre-diluted/lysed samples. Despite these current challenges, multiple advances have been made in the development of devices for rare cell capture and the subsequent elucidation of new biological phenomena; this article serves to highlight this progress as well as the electrokinetic and non-electrokinetic methods that can potentially be combined to improve performance in future studies. PMID:21532971

  10. A Study of Evaluation and Management of Rare Congenital Breast Diseases

    PubMed Central

    Mehta, Sudhir Kumar; Bala, Jyoti; Zaman, Muzzafar; Mittal, Amit; Gupta, Guarav; Rudra, Samer; Singal, Samita

    2016-01-01

    carcinoma are common entities to come across everywhere but accessory breasts are rarely encountered especially in rural areas because of less awareness. The study found that there was tendency to neglect the swelling as there were minimal symptoms present. We also came across a rare entity, accessory breast and accessory nipples. A clinician should not ignore such cases taking as simple swelling because of chances of discovering a malignancy can occur. PMID:27891392

  11. A Study of Evaluation and Management of Rare Congenital Breast Diseases.

    PubMed

    Singal, Rikki; Mehta, Sudhir Kumar; Bala, Jyoti; Zaman, Muzzafar; Mittal, Amit; Gupta, Guarav; Rudra, Samer; Singal, Samita

    2016-10-01

    accessory breasts are rarely encountered especially in rural areas because of less awareness. The study found that there was tendency to neglect the swelling as there were minimal symptoms present. We also came across a rare entity, accessory breast and accessory nipples. A clinician should not ignore such cases taking as simple swelling because of chances of discovering a malignancy can occur.

  12. Rare-Variant Association Analysis: Study Designs and Statistical Tests

    PubMed Central

    Lee, Seunggeung; Abecasis, Gonçalo R.; Boehnke, Michael; Lin, Xihong

    2014-01-01

    Despite the extensive discovery of trait- and disease-associated common variants, much of the genetic contribution to complex traits remains unexplained. Rare variants can explain additional disease risk or trait variability. An increasing number of studies are underway to identify trait- and disease-associated rare variants. In this review, we provide an overview of statistical issues in rare-variant association studies with a focus on study designs and statistical tests. We present the design and analysis pipeline of rare-variant studies and review cost-effective sequencing designs and genotyping platforms. We compare various gene- or region-based association tests, including burden tests, variance-component tests, and combined omnibus tests, in terms of their assumptions and performance. Also discussed are the related topics of meta-analysis, population-stratification adjustment, genotype imputation, follow-up studies, and heritability due to rare variants. We provide guidelines for analysis and discuss some of the challenges inherent in these studies and future research directions. PMID:24995866

  13. State of rare disease management in Southeast Asia.

    PubMed

    Shafie, Asrul Akmal; Chaiyakunapruk, Nathorn; Supian, Azuwana; Lim, Jeremy; Zafra, Matt; Hassali, Mohamed Azmi Ahmad

    2016-08-02

    Rare diseases, also referred to as orphan diseases, are characterised by their low prevalence with majority of them are chronically debilitating and life threatening. Given the low prevalence and the widely dispersed but very small patient base for each disease, there may often be a disproportion in the availability of treatments and resources to manage patients, spur research and train experts. This is especially true in Southeast Asian countries that are currently in the process of implementing or revising their universal health coverage schemes. This paper aims to examine the status of rare disease management in Southeast Asian countries. It will serve as the basis for a more active discussion on how countries in the region can address an under-recognised rare disease burden and enhance national and regional capacities. The study consists of literature reviews and key stakeholders interviews in six focus countries, including the Philippines, Singapore, Malaysia, Indonesia, Vietnam, and Thailand and five countries as best practice, comprising of France, Canada, Australia, Taiwan, and South Korea. Rare disease management initiatives across each country were examined based on the World Health Organization's framework for action in strengthening health systems. The results suggest rare disease management remains challenging across Southeast Asia, as many of the focus countries face fundamental issues from basic healthcare systems to funding. Nonetheless, there are substantial improvement opportunities, including leveraging best practices from around the world and organising a multi-stakeholder and regional approach and strategy. Southeast Asian countries have made significant progress in the management of rare disease, but there remain key areas for substantial development opportunities.

  14. Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion

    PubMed Central

    Hall, Michael J; Innocent, Julie; Rybak, Christina; Veloski, Colleen; Scott, Walter J; Wu, Hong; Ridge, John A; Hoffman, John P; Borghaei, Hossein; Turaka, Aruna; Daly, Mary B

    2015-01-01

    Introduction Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. Case report A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo–oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A). Discussion Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A) in a male proband meeting the criteria for clinical MEN1 syndrome. Functional analysis performed on the stable mutant protein showed selective disruption of the transforming growth factor beta signaling pathway, yet it maintained its wild-type ability to inhibit nuclear factor kappa B and to suppress JunD transcriptional activity. Conclusion To our knowledge, this is the first report of MEN1 syndrome associated with bilateral granulosa cell malignancy. We postulate that

  15. Discovering Inexpensive, Effective Catalysts for Solar Energy Conversion: An Authentic Research Laboratory Experience

    ERIC Educational Resources Information Center

    Shaner, Sarah E.; Hooker, Paul D.; Nickel, Anne-Marie; Leichtfuss, Amanda R.; Adams, Carissa S.; de la Cerda, Dionisia; She, Yuqi; Gerken, James B.; Pokhrel, Ravi; Ambrose, Nicholas J.; Khaliqi, David; Stahl, Shannon S.; Schuttlefield Christus, Jennifer D.

    2016-01-01

    Electrochemical water oxidation is a major focus of solar energy conversion efforts. A new laboratory experiment has been developed that utilizes real-time, hands-on research to discover catalysts for solar energy conversion. The HARPOON, or Heterogeneous Anodes Rapidly Perused for Oxygen Overpotential Neutralization, experiment allows an array of…

  16. A Rare Disease in Adult: Langerhans Cell Histiocytosis

    PubMed Central

    Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Koroglu, Mustafa; Kaya, Emin; Unlu, Serkan

    2013-01-01

    Langerhans cell histiocytosis is a rare histiocytic disorder and has been diagnosed in all age groups, but is most common in children. This disease is very rare in adults. We presented a patient who was 62 years old man diagnosed langerhans cell histiocytosis. PMID:29147350

  17. A Virtual Screen Discovers Novel, Fragment-Sized Inhibitors of Mycobacterium tuberculosis InhA

    PubMed Central

    Perryman, Alexander L.; Yu, Weixuan; Wang, Xin; Ekins, Sean; Forli, Stefano; Li, Shao-Gang; Freundlich, Joel S.; Tonge, Peter J.; Olson, Arthur J.

    2015-01-01

    Isoniazid (INH) is usually administered to treat latent Mycobacterium tuberculosis (Mtb) infections, and is used in combination therapy to treat active tuberculosis disease (TB). Unfortunately, resistance to this drug is hampering its clinical effectiveness. INH is a prodrug that must be activated by Mtb catalase peroxidase (KatG) before it can inhibit InhA (Mtb enoyl-acyl-carrier-protein reductase). Isoniazid-resistant cases of TB found in clinical settings usually involve mutations in or deletion of katG, which abrogate INH activation. Compounds that inhibit InhA without requiring prior activation by KatG would not be affected by this resistance mechanism and hence would display continued potency against these drug-resistant isolates of Mtb. Virtual screening experiments versus InhA in the GO Fight Against Malaria project (GO FAM) were designed to discover new scaffolds that display base stacking interactions with the NAD cofactor. GO FAM experiments included targets from other pathogens, including Mtb, when they had structural similarity to a malaria target. Eight of the sixteen soluble compounds identified by docking against InhA plus visual inspection were modest inhibitors and did not require prior activation by KatG. The best two inhibitors discovered are both fragment-sized compounds and displayed Ki values of 54 and 59 μM, respectively. Importantly, the novel inhibitors discovered have low structural similarity to known InhA inhibitors and, thus, help expand the number of chemotypes on which future medicinal chemistry efforts can be focused. These new fragment hits could eventually help advance the fight against INH-resistant Mtb strains, which pose a significant global health threat. PMID:25636146

  18. Drug discovery and development for rare genetic disorders.

    PubMed

    Sun, Wei; Zheng, Wei; Simeonov, Anton

    2017-09-01

    Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed. Rare diseases are usually genetic diseases; hence, employing pharmacogenetics to develop treatments and using whole genome sequencing to identify the etiologies for such diseases are appropriate strategies to exploit. Beginning with high throughput screening of small molecules, the benefits and challenges of target-based and phenotypic screens are discussed. Explanations and examples of drug repurposing are given; drug repurposing as an approach to quickly move programs to clinical trials is evaluated. Consideration is given to the category of biologics which include gene therapy, recombinant proteins, and autologous transplants. Disease models, including animal models and induced pluripotent stem cells (iPSCs) derived from patients, are surveyed. Finally, the role of biomarkers in drug discovery and development, as well as clinical trials, is elucidated. © 2017 Wiley Periodicals, Inc.

  19. Long Noncoding RNAs AC009014.3 and Newly Discovered XPLAID Differentiate Aggressive and Indolent Prostate Cancers.

    PubMed

    Cesnik, Anthony J; Yang, Bing; Truong, Andrew; Etheridge, Tyler; Spiniello, Michele; Steinbrink, Maisie I; Shortreed, Michael R; Frey, Brian L; Jarrard, David F; Smith, Lloyd M

    2018-06-01

    The molecular mechanisms underlying aggressive versus indolent disease are not fully understood. Recent research has implicated a class of molecules known as long noncoding RNAs (lncRNAs) in tumorigenesis and progression of cancer. Our objective was to discover lncRNAs that differentiate aggressive and indolent prostate cancers. We analyzed paired tumor and normal tissues from six aggressive Gleason score (GS) 8-10 and six indolent GS 6 prostate cancers. Extracted RNA was split for poly(A)+ and ribosomal RNA depletion library preparations, followed byRNA sequencing (RNA-Seq) using an Illumina HiSeq 2000. We developed an RNA-Seq data analysis pipeline to discover and quantify these molecules. Candidate lncRNAs were validated using RT-qPCR on 87 tumor tissue samples: 28 (GS 6), 28 (GS 3+4), 6 (GS 4+3), and 25 (GS 8-10). Statistical correlations between lncRNAs and clinicopathologic variables were tested using ANOVA. The 43 differentially expressed (DE) lncRNAs between aggressive and indolent prostate cancers included 12 annotated and 31 novel lncRNAs. The top six DE lncRNAs were selected based on large, consistent fold-changes in the RNA-Seq results. Three of these candidates passed RT-qPCR validation, including AC009014.3 (P < .001 in tumor tissue) and a newly discovered X-linked lncRNA named XPLAID (P = .049 in tumor tissue and P = .048 in normal tissue). XPLAID and AC009014.3 show promise as prognostic biomarkers. We discovered several dozen lncRNAs that distinguish aggressive and indolent prostate cancers, of which four were validated using RT-qPCR. The investigation into their biology is ongoing. Published by Elsevier Inc.

  20. Paediatric genomics: diagnosing rare disease in children.

    PubMed

    Wright, Caroline F; FitzPatrick, David R; Firth, Helen V

    2018-05-01

    The majority of rare diseases affect children, most of whom have an underlying genetic cause for their condition. However, making a molecular diagnosis with current technologies and knowledge is often still a challenge. Paediatric genomics is an immature but rapidly evolving field that tackles this issue by incorporating next-generation sequencing technologies, especially whole-exome sequencing and whole-genome sequencing, into research and clinical workflows. This complex multidisciplinary approach, coupled with the increasing availability of population genetic variation data, has already resulted in an increased discovery rate of causative genes and in improved diagnosis of rare paediatric disease. Importantly, for affected families, a better understanding of the genetic basis of rare disease translates to more accurate prognosis, management, surveillance and genetic advice; stimulates research into new therapies; and enables provision of better support.

  1. Rare-earth metal prices in the USA ca. 1960 to 1994

    USGS Publications Warehouse

    Hedrick, James B.

    1997-01-01

    Rare-earth metal prices were compiled from the late 1950s and early 1960s through 1994. Although commercial demand for rare-earth metals began in 1908, as the alloy mischmetal, commercial quantities of a wide range of individual rare-earth metals were not available until the late 1950s. The discovery of a large, high-grade rare-earth deposit at Mountain Pass. CA, USA, in 1949, was significant because it led to the production of commercial quantities or rare-earth elements that reduced prices and encouraged wider application of the materials. The availability of ore from Mountain Pass, and other large rare-earth deposits, especially those in Australia and China, has provided the world with abundant resources for rare-earth metal production. This availability, coupled with improved technology from Government and private-sector metallurgical research, has resulted in substantial decreases in rare-earth metal prices since the late 1950s and early 1960s. Price series for the individual rare-earth metals (except promethium) are quoted on a kilogram basis from the late 1950s and early 1960s through 1994. Prices are given in US dollars on an actual and constant dollar basis. Industrial and economic factors affecting prices during this time period are examined.

  2. Rare-earth metal prices in the USA ca. 1960 to 1994

    USGS Publications Warehouse

    Hedrick, J.B.

    1997-01-01

    Rare-earth metal prices were compiled from the late 1950s and early 1960s through 1994. Although commercial demand for rare-earth metals began in 1908, as the alloy mischmetal, commercial quantities of a wide range of individual rare-earth metals were not available until the late 1950s. The discovery of a large, high-grade rare-earth deposit at Mountain Pass, CA, USA, in 1949, was significant because it led to the production of commercial quantities of rare-earth elements that reduced prices and encouraged wider application of the materials. The availability of ore from Mountain Pass, and other large rare-earth deposits, especially those in Australia and China, has provided the world with abundant resources for rare-earth metal production. This availability, coupled with improved technology from Government and private-sector metallurgical research, has resulted in substantial decreases in rare-earth metal prices since the late 1950s and early 1960s. Price series for the individual rare-earth metals (except promethium) are quoted on a kilogram basis from the late 1950s and early 1960s through 1994. Prices are given in US dollars on an actual and constant dollar basis. Industrial and economic factors affecting prices during this time period are examined.

  3. Two superluminous supernovae from the early universe discovered by the supernova legacy survey

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

    Howell, D. A.; Kasen, D.; Lidman, C.

    2013-12-20

    We present spectra and light curves of SNLS 06D4eu and SNLS 07D2bv, two hydrogen-free superluminous supernovae (SNe) discovered by the Supernova Legacy Survey. At z = 1.588, SNLS 06D4eu is the highest redshift superluminous SN with a spectrum, at M{sub U} = –22.7 it is one of the most luminous SNe ever observed, and it gives a rare glimpse into the rest-frame ultraviolet where these SNe put out their peak energy. SNLS 07D2bv does not have a host galaxy redshift, but on the basis of the SN spectrum, we estimate it to be at z ∼ 1.5. Both SNe havemore » similar observer-frame griz light curves, which map to rest-frame light curves in the U band and UV, rising in ∼20 rest-frame days or longer and declining over a similar timescale. The light curves peak in the shortest wavelengths first, consistent with an expanding blackbody starting near 15,000 K and steadily declining in temperature. We compare the spectra with theoretical models, and we identify lines of C II, C III, Fe III, and Mg II in the spectra of SNLS 06D4eu and SCP 06F6 and find that they are consistent with an expanding explosion of only a few solar masses of carbon, oxygen, and other trace metals. Thus, the progenitors appear to be related to those suspected for SNe Ic. A high kinetic energy, 10{sup 52} erg, is also favored. Normal mechanisms of powering core-collapse or thermonuclear SNe do not seem to work for these SNe. We consider models powered by {sup 56}Ni decay and interaction with circumstellar material, but we find that the creation and spin-down of a magnetar with a period of 2 ms, a magnetic field of 2 × 10{sup 14} G, and a 3 M {sub ☉} progenitor provides the best fit to the data.« less

  4. Incorporating Topic Assignment Constraint and Topic Correlation Limitation into Clinical Goal Discovering for Clinical Pathway Mining.

    PubMed

    Xu, Xiao; Jin, Tao; Wei, Zhijie; Wang, Jianmin

    2017-01-01

    Clinical pathways are widely used around the world for providing quality medical treatment and controlling healthcare cost. However, the expert-designed clinical pathways can hardly deal with the variances among hospitals and patients. It calls for more dynamic and adaptive process, which is derived from various clinical data. Topic-based clinical pathway mining is an effective approach to discover a concise process model. Through this approach, the latent topics found by latent Dirichlet allocation (LDA) represent the clinical goals. And process mining methods are used to extract the temporal relations between these topics. However, the topic quality is usually not desirable due to the low performance of the LDA in clinical data. In this paper, we incorporate topic assignment constraint and topic correlation limitation into the LDA to enhance the ability of discovering high-quality topics. Two real-world datasets are used to evaluate the proposed method. The results show that the topics discovered by our method are with higher coherence, informativeness, and coverage than the original LDA. These quality topics are suitable to represent the clinical goals. Also, we illustrate that our method is effective in generating a comprehensive topic-based clinical pathway model.

  5. Incorporating Topic Assignment Constraint and Topic Correlation Limitation into Clinical Goal Discovering for Clinical Pathway Mining

    PubMed Central

    Xu, Xiao; Wei, Zhijie

    2017-01-01

    Clinical pathways are widely used around the world for providing quality medical treatment and controlling healthcare cost. However, the expert-designed clinical pathways can hardly deal with the variances among hospitals and patients. It calls for more dynamic and adaptive process, which is derived from various clinical data. Topic-based clinical pathway mining is an effective approach to discover a concise process model. Through this approach, the latent topics found by latent Dirichlet allocation (LDA) represent the clinical goals. And process mining methods are used to extract the temporal relations between these topics. However, the topic quality is usually not desirable due to the low performance of the LDA in clinical data. In this paper, we incorporate topic assignment constraint and topic correlation limitation into the LDA to enhance the ability of discovering high-quality topics. Two real-world datasets are used to evaluate the proposed method. The results show that the topics discovered by our method are with higher coherence, informativeness, and coverage than the original LDA. These quality topics are suitable to represent the clinical goals. Also, we illustrate that our method is effective in generating a comprehensive topic-based clinical pathway model. PMID:29065617

  6. Rare Earth Optical Temperature Sensor

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L.; Wolford, David S.

    2000-01-01

    A new optical temperature sensor suitable for high temperatures (greater than 1700 K) and harsh environments is introduced. The key component of the sensor is the rare earth material contained at the end of a sensor that is in contact with the sample being measured. The measured narrow wavelength band emission from the rare earth is used to deduce the sample temperature. A simplified relation between the temperature and measured radiation was verified experimentally. The upper temperature limit of the sensor is determined by material limits to be approximately 2000 C. The lower limit, determined by the minimum detectable radiation, is found to be approximately 700 K. At high temperatures 1 K resolution is predicted. Also, millisecond response times are calculated.

  7. [Effects of arbuscular mycorrhizal fungi on the growth and rare earth elements uptake of soybean grown in rare earth mine tailings].

    PubMed

    Guo, Wei; Zhao, Ren-xin; Zhao, Wen-jing; Fu, Rui-ying; Guo, Jiang-yuan; Zhang, Jun

    2013-05-01

    A greenhouse pot experiment was conducted to investigate the influence of arbuscular mycorrhizal (AM) fungi Glomus versiforme on the plant growth, nutrient uptake, C: N: P stoichiometric, uptake of heavy metals and rare earth elements by soybean (Glycine max) grown in rare earth mine tailings. The aim was to provide a basis for the revegetation of rare earth mine tailings. The results indicated that soybean had a high mycorrhizal colonization and symbiotic associations were successfully established with G. versiforme, with an average rate of approximately 67%. The colonization of G. versiforme significantly promoted the growth of soybean, increased P, K contents, and decreased C: N: P ratios, supporting the growth rate hypothesis. Inoculation with G. versiforme significantly decreased shoots and roots La, Ce, Pr and Nd concentrations of soybean compared to the control treatment. However, inoculation with G. versiforme had no significant effect on the heavy metal concentrations, except for significantly decreased shoot Fe and Cr concentrations and increased root Cd concentrations. The experiment demonstrates that AM fungi have a potential role for soybean to adapt the composite adversity of rare earth tailings and play a positive role in revegetation of rare earth mine tailings. Further studies on the role of AM fungi under natural conditions should be conducted.

  8. ASASSN1: Bright Comet Discovered by the All Sky Automated Survey for SuperNovae

    NASA Astrophysics Data System (ADS)

    Prieto, JJ. L.; Shappee, B. J.; Brimacombe, J.; Stanek, K. Z.; Chen, Ping; Dong, Subo; Holoien, T. W.-S.; Kochanek, C. S.; Brown, J. S.; Shields, J. V.; Thompson, T. A.

    2017-07-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from the quadruple 14-cm "Cassius" telescope on Cerro Tololo, Chile, we discovered a new moving transient source, now confirmed as a comet.

  9. An ensemble heterogeneous classification methodology for discovering health-related knowledge in social media messages.

    PubMed

    Tuarob, Suppawong; Tucker, Conrad S; Salathe, Marcel; Ram, Nilam

    2014-06-01

    The role of social media as a source of timely and massive information has become more apparent since the era of Web 2.0.Multiple studies illustrated the use of information in social media to discover biomedical and health-related knowledge.Most methods proposed in the literature employ traditional document classification techniques that represent a document as a bag of words.These techniques work well when documents are rich in text and conform to standard English; however, they are not optimal for social media data where sparsity and noise are norms.This paper aims to address the limitations posed by the traditional bag-of-word based methods and propose to use heterogeneous features in combination with ensemble machine learning techniques to discover health-related information, which could prove to be useful to multiple biomedical applications, especially those needing to discover health-related knowledge in large scale social media data.Furthermore, the proposed methodology could be generalized to discover different types of information in various kinds of textual data. Social media data is characterized by an abundance of short social-oriented messages that do not conform to standard languages, both grammatically and syntactically.The problem of discovering health-related knowledge in social media data streams is then transformed into a text classification problem, where a text is identified as positive if it is health-related and negative otherwise.We first identify the limitations of the traditional methods which train machines with N-gram word features, then propose to overcome such limitations by utilizing the collaboration of machine learning based classifiers, each of which is trained to learn a semantically different aspect of the data.The parameter analysis for tuning each classifier is also reported. Three data sets are used in this research.The first data set comprises of approximately 5000 hand-labeled tweets, and is used for cross validation of the

  10. Discovering Tradeoffs, Vulnerabilities, and Dependencies within Water Resources Systems

    NASA Astrophysics Data System (ADS)

    Reed, P. M.

    2015-12-01

    There is a growing recognition and interest in using emerging computational tools for discovering the tradeoffs that emerge across complex combinations infrastructure options, adaptive operations, and sign posts. As a field concerned with "deep uncertainties", it is logically consistent to include a more direct acknowledgement that our choices for dealing with computationally demanding simulations, advanced search algorithms, and sensitivity analysis tools are themselves subject to failures that could adversely bias our understanding of how systems' vulnerabilities change with proposed actions. Balancing simplicity versus complexity in our computational frameworks is nontrivial given that we are often exploring high impact irreversible decisions. It is not always clear that accepted models even encompass important failure modes. Moreover as they become more complex and computationally demanding the benefits and consequences of simplifications are often untested. This presentation discusses our efforts to address these challenges through our "many-objective robust decision making" (MORDM) framework for the design and management water resources systems. The MORDM framework has four core components: (1) elicited problem conception and formulation, (2) parallel many-objective search, (3) interactive visual analytics, and (4) negotiated selection of robust alternatives. Problem conception and formulation is the process of abstracting a practical design problem into a mathematical representation. We build on the emerging work in visual analytics to exploit interactive visualization of both the design space and the objective space in multiple heterogeneous linked views that permit exploration and discovery. Many-objective search produces tradeoff solutions from potentially competing problem formulations that can each consider up to ten conflicting objectives based on current computational search capabilities. Negotiated design selection uses interactive visualization

  11. Risk of appendicitis in patients with incidentally discovered appendicoliths.

    PubMed

    Khan, Muhammad Sohaib; Chaudhry, Mustafa Belal Hafeez; Shahzad, Noman; Tariq, Marvi; Memon, Wasim Ahmed; Alvi, Abdul Rehman

    2018-01-01

    An appendicolith-related appendiceal obstruction leading to appendicitis is a commonly encountered surgical emergency that has clear evidence-based management plans. However, there is no consensus on management of asymptomatic patients when appendicoliths are found incidentally. The objective of this study was to determine the risk of appendicitis in patients with an incidental finding of the appendicolith. A retrospective matched cohort study of patients with appendicolith discovered incidentally on computed tomographic scan from January 2008 to December 2014 at our institution was completed. The size and position of the appendicolith were ascertained. The study group was matched by age and gender to a control group. Both groups were contacted and interviewed regarding development of appendicitis. In total, 111 patients with appendicolith were successfully contacted and included in the study. Mean age was found to be 38 ± 15 y with 36 (32%) of the study population being females. Mean length of appendix was 66 ± 16 mm, and mean width was 5.8 ± 0.9 mm. Mean size of the appendicolith was 3.6 ± 1.1 mm (1.4-7.8 mm). Fifty-eight percent of appendicoliths was located at the proximal end or whole of appendix, 31% at mid area, and 11% at the distal end of appendix. All patients of the study and control groups were contacted, and at a mean follow-up of 4.0 ± 1.7 y, there was no occurrence of acute appendicitis in either group. Patients with incidentally discovered appendicolith on radiological imaging did not develop appendicitis. Hence, the risk of developing acute appendicitis for these patients does not seem higher than the general population. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Discovering shared segments on the migration route of the bar-headed goose by time-based plane-sweeping trajectory clustering

    USGS Publications Warehouse

    Luo, Ze; Baoping, Yan; Takekawa, John Y.; Prosser, Diann J.

    2012-01-01

    We propose a new method to help ornithologists and ecologists discover shared segments on the migratory pathway of the bar-headed geese by time-based plane-sweeping trajectory clustering. We present a density-based time parameterized line segment clustering algorithm, which extends traditional comparable clustering algorithms from temporal and spatial dimensions. We present a time-based plane-sweeping trajectory clustering algorithm to reveal the dynamic evolution of spatial-temporal object clusters and discover common motion patterns of bar-headed geese in the process of migration. Experiments are performed on GPS-based satellite telemetry data from bar-headed geese and results demonstrate our algorithms can correctly discover shared segments of the bar-headed geese migratory pathway. We also present findings on the migratory behavior of bar-headed geese determined from this new analytical approach.

  13. Classic tongue lipoma: a common tumour at a rare site

    PubMed Central

    Magadum, Dilip; Sanadi, Appasab; Agrawal, Jiwanasha Manish; Agrawal, Manish Suresh

    2013-01-01

    Lipoma is the commonest benign tumour occurring at any anatomical site where fat is present, but occurrence in the oral cavity is rare. Tongue which is totally devoid of fat cells is a rare site for lipoma. This is one such rare case of the universal tumour, presenting at the lateral margin of the tongue, for which complete tumour excision was done. Macroscopically the mass had a hard consistency and measured 3.0×2.0 cm. From microscopic examination, diagnosis of lipoma was made. Recurrence of tongue lipoma is rare. PMID:23370950

  14. Innovative measures to combat rare diseases in China: The national rare diseases registry system, larger-scale clinical cohort studies, and studies in combination with precision medicine research.

    PubMed

    Song, Peipei; He, Jiangjiang; Li, Fen; Jin, Chunlin

    2017-02-01

    China is facing the great challenge of treating the world's largest rare disease population, an estimated 16 million patients with rare diseases. One effort offering promise has been a pilot national project that was launched in 2013 and that focused on 20 representative rare diseases. Another government-supported special research program on rare diseases - the "Rare Diseases Clinical Cohort Study" - was launched in December 2016. According to the plan for this research project, the unified National Rare Diseases Registry System of China will be established as of 2020, and a large-scale cohort study will be conducted from 2016 to 2020. The project plans to develop 109 technical standards, to establish and improve 2 national databases of rare diseases - a multi-center clinical database and a biological sample library, and to conduct studies on more than 50,000 registered cases of 50 different rare diseases. More importantly, this study will be combined with the concept of precision medicine. Chinese population-specific basic information on rare diseases, clinical information, and genomic information will be integrated to create a comprehensive predictive model with a follow-up database system and a model to evaluate prognosis. This will provide the evidence for accurate classification, diagnosis, treatment, and estimation of prognosis for rare diseases in China. Numerous challenges including data standardization, protecting patient privacy, big data processing, and interpretation of genetic information still need to be overcome, but research prospects offer great promise.

  15. New results on the exotic galaxy `Speca' and discovering many more Specas with RAD@home network

    NASA Astrophysics Data System (ADS)

    Hota, Ananda; Croston, Judith H.; Ohyama, Youichi; Stalin, C. S.; Hardcastle, Martin J.; Konar, Chiranjib; Aravind, R. P.; Agarwal, Sheena M.; Dharmik Bhoga, Sai Arun; Dabhade, Pratik; Kamble, Amit A.; Mohanty, Pradeepta K.; Mukherjee, Alok; Pandey, Akansha V.; Patra, Alakananda; Pechetti, Renuka; Raut, Shrishail S.; Sushma, V.; Vaddi, Sravani; Verma, Nishchhal

    We present the first report on an innovative new project named "RAD@home", a citizen-science research collaboratory built on free web-services like Facebook, Google, Skype, NASA Skyview, NED, TGSS etc.. This is the first of its kind in India, a zero-funded, zero-infrastructure, human-resource network to educate and directly involve in research, hundreds of science-educated under-graduate population of India, irrespective of their official employment and home-location with in the country. Professional international collaborators are involved in follow up observation and publication of the objects discovered by the collaboratory. We present here ten newly found candidate episodic radio galaxies, already proposed to GMRT, and ten more interesting cases which includes, bent-lobe radio galaxies located in new Mpc-scale filaments, likely tracing cosmological cluster accretion from the cosmic web. Two new Speca-like rare spiral-host large radio galaxies have also been been reported here. Early analyses from our follow up observations with the Subaru and XMM-Newton telescopes have revealed that Speca is likely a new entry to the cluster and is a fast rotating, extremely massive, star forming disk galaxy. Speca-like massive galaxies with giant radio lobes, are possibly remnants of luminous quasars in the early Universe or of first supermassive black holes with in first masssve galaxies. As discoveries of Speca-like galaxies did not require new data from big telescopes, but free archival radio-optical data, these early results demonstrate the discovery potential of RAD@home and how it can help resource-rich professionals, as well as demonstrate a model of academic-growth for resource-poor people in the underdeveloped regions via Internet.

  16. Research methods to change clinical practice for patients with rare cancers.

    PubMed

    Billingham, Lucinda; Malottki, Kinga; Steven, Neil

    2016-02-01

    Rare cancers are a growing group as a result of reclassification of common cancers by molecular markers. There is therefore an increasing need to identify methods to assess interventions that are sufficiently robust to potentially affect clinical practice in this setting. Methods advocated for clinical trials in rare diseases are not necessarily applicable in rare cancers. This Series paper describes research methods that are relevant for rare cancers in relation to the range of incidence levels. Strategies that maximise recruitment, minimise sample size, or maximise the usefulness of the evidence could enable the application of conventional clinical trial design to rare cancer populations. Alternative designs that address specific challenges for rare cancers with the aim of potentially changing clinical practice include Bayesian designs, uncontrolled n-of-1 trials, and umbrella and basket trials. Pragmatic solutions must be sought to enable some level of evidence-based health care for patients with rare cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Research on economy and social exclusion: China dolls and rare diseases.

    PubMed

    Matsui, Akihiko

    2013-02-01

    The second workshop on "Research on Economy And Social Exclusion (REASE)" was held in the University of Tokyo on January 26, 2013. Focusing on rare diseases and disorders in China, three speakers from China introduced the current status of rare diseases and the challenge of support organizations for patients with rare disease and disorders in China, and especially pointed out some important issues associated with rare diseases and disorders in China. From the viewpoint of economics, this paper discusses some of the important issues of rare diseases and disorders in China raised in this workshop, especially from the aspects of economy of scale and orphan drugs, and the emergence of stigma from discrimination. It was shown that international coordination and cooperation are called for in order to give a proper incentive to the drug industries to create new drugs for rare diseases, and suggested that an important step toward inclusion is to reduce stigma by making rare diseases visible as much as possible.

  18. Rare Plants of the Redwood Forest and Forest Management Effects

    Treesearch

    Teresa Sholars; Clare Golec

    2007-01-01

    Coast redwood forests are predominantly a timber managed habitat type, subjected to repeated disturbances and short rotation periods. What does this repeated disturbance mean for rare plants associated with the redwood forests? Rare plant persistence through forest management activities is influenced by many factors. Persistence of rare plants in a managed landscape is...

  19. Economic Modeling Considerations for Rare Diseases.

    PubMed

    Pearson, Isobel; Rothwell, Ben; Olaye, Andrew; Knight, Christopher

    2018-05-01

    To identify challenges that affect the feasibility and rigor of economic models in rare diseases and strategies that manufacturers have employed in health technology assessment submissions to demonstrate the value of new orphan products that have limited study data. Targeted reviews of PubMed, the National Institute for Health and Care Excellence's (NICE's) Highly Specialised Technologies (HST), and the Scottish Medicines Consortium's (SMC's) ultra-orphan submissions were performed. A total of 19 PubMed studies, 3 published NICE HSTs, and 11 ultra-orphan SMC submissions were eligible for inclusion. In rare diseases, a number of different factors may affect the model's ability to comply with good practice recommendations. Many products for the treatment of rare diseases have an incomplete efficacy and safety profile at product launch. In addition, there is often limited available natural history and epidemiology data. Information on the direct and indirect cost burden of an orphan disease also may be limited, making it difficult to estimate the potential economic benefit of treatment. These challenges can prevent accurate estimation of a new product's benefits in relation to costs. Approaches that can address such challenges include using patient and/or clinician feedback to inform model assumptions; data from disease analogues; epidemiological techniques, such as matching-adjusted indirect comparison; and long-term data collection. Modeling in rare diseases is often challenging; however, a number of approaches are available to support the development of model structures and the collation of input parameters and to manage uncertainty. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  20. Development of Korean Rare Disease Knowledge Base

    PubMed Central

    Seo, Heewon; Kim, Dokyoon; Chae, Jong-Hee; Kang, Hee Gyung; Lim, Byung Chan; Cheong, Hae Il

    2012-01-01

    Objectives Rare disease research requires a broad range of disease-related information for the discovery of causes of genetic disorders that are maladies caused by abnormalities in genes or chromosomes. A rarity in cases makes it difficult for researchers to elucidate definite inception. This knowledge base will be a major resource not only for clinicians, but also for the general public, who are unable to find consistent information on rare diseases in a single location. Methods We design a compact database schema for faster querying; its structure is optimized to store heterogeneous data sources. Then, clinicians at Seoul National University Hospital (SNUH) review and revise those resources. Additionally, we integrated other sources to capture genomic resources and clinical trials in detail on the Korean Rare Disease Knowledge base (KRDK). Results As a result, we have developed a Web-based knowledge base, KRDK, suitable for study of Mendelian diseases that commonly occur among Koreans. This knowledge base is comprised of disease summary and review, causal gene list, laboratory and clinic directory, patient registry, and so on. Furthermore, database for analyzing and giving access to human biological information and the clinical trial management system are integrated on KRDK. Conclusions We expect that KRDK, the first rare disease knowledge base in Korea, may contribute to collaborative research and be a reliable reference for application to clinical trials. Additionally, this knowledge base is ready for querying of drug information so that visitors can search a list of rare diseases that is relative to specific drugs. Visitors can have access to KRDK via http://www.snubi.org/software/raredisease/. PMID:23346478

  1. The eminent anatomists who discovered the upper oesophageal sphincter.

    PubMed

    Marchese-Ragona, R; Ottaviano, G; Masiero, S; Staffieri, C; Martini, A; Staffieri, A; Mion, M; Zaninotto, G; Restivo, D A

    2014-10-01

    To discover the anatomist who first identified the upper oesophageal sphincter. The authors searched dozens of antique anatomy textbooks kept in the old section of the 'Vincenzo Pinali' Medical Library of Padua University, looking for descriptions of the upper oesophageal sphincter. The oesophageal sphincter was drawn correctly only in 1601, by Julius Casserius, in the book De vocis auditusque organis historia anatomica… (which translates as 'An Anatomical History on the Organs of Voice and Hearing …'), and was properly described by Antonio Maria Valsalva in 1704 in the book De aure humana tractatus… ('Treatise on the Human Ear …'). Anatomists Casserius and Valsalva can be considered the discoverers of the 'oesophageal sphincter'.

  2. Insights into rare diseases from social media surveys.

    PubMed

    Davies, William

    2016-11-09

    The internet, and social media platforms, are increasingly being used by substantial sectors of the worldwide population. By engaging effectively with online and social media, scientists and clinicians can obtain unprecedented access to relatively large cohorts of individuals with rare diseases, as well as their relatives, carers and professionals involved in their healthcare. Online surveys of these stakeholder groups may provide important new insights into rare conditions and their management relatively quickly and easily, with the possibility of rapid translation into healthcare interventions and policy. Here, I describe our recent positive experience with the online survey approach to a rare disease (X-linked ichthyosis), and review its advantages and limitations.

  3. Squeezing clathrate cages to host trivalent rare-earth guests

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

    Wang, Jian; He, Yuping; Mordvinova, Natalia E.

    Strike difference of the trivalent rare-earth cations from their alkali and alkaline-earth peers is in the presence of localized 4f-electrons and strong spin-orbit coupling. Placing trivalent rare-earth cations inside the fullerene molecules or in between the blocks of itinerant magnetic intermetallics gave rise to plethora of fascinating properties and materials. A long-time missing but hardly desired piece is the semiconducting or metallic compound where rare-earth cations are situated inside the oversized polyhedral cages of three-dimensional framework. In this work we present a synthesis of such compounds, rare-earth containing clathrates Ba 8-xR xCu 16P 30. The unambiguous proofs of their compositionmore » and crystal structure were achieved by a combination of synchrotron powder diffraction, time-of-flight neutron powder diffraction, scanning-transmission electron microscopy, and electron energy-loss spectroscopy. Our quantum-mechanical calculations and experimental characterizations show that the incorporation of the rare-earth cations significantly enhances the hole mobility and concentration which results in the drastic increase in the thermoelectric performance.« less

  4. Discovering the Thermodynamics of Simultaneous Equilibria: An Entropy Analysis Activity Involving Consecutive Equilibria

    ERIC Educational Resources Information Center

    Bindel, Thomas H.

    2007-01-01

    An activity is presented in which the thermodynamics of simultaneous, consecutive equilibria are explored. The activity is appropriate for second-year high school or AP chemistry. Students discover that a reactant-favored (entropy-diminishing or endergonic) reaction can be caused to happen if it is coupled with a product-favored reaction of…

  5. Examining Pre-K Professional Development Programs: Discovering the Road to Exceptional Instructional Practices

    ERIC Educational Resources Information Center

    Williams, Sheila D.

    2016-01-01

    The purpose of this qualitative research study was to discover and interpret the experiences of pre-k teachers in an urban school district located in a Northeastern region of the United States. Using a basic qualitative research design, fifteen participants were recruited by a purposeful sampling method to be interviewed after the implementation…

  6. A population-based registry as a source of health indicators for rare diseases: the ten-year experience of the Veneto Region’s rare diseases registry

    PubMed Central

    2014-01-01

    Background Although rare diseases have become a major public health issue, there is a paucity of population-based data on rare diseases. The aim of this epidemiological study was to provide descriptive figures referring to a sizable group of unrelated rare diseases. Methods Data from the rare diseases registry established in the Veneto Region of north-east Italy (population 4,900,000), referring to the years from 2002 to 2012, were analyzed. The registry is based on a web-based system accessed by different users. Cases are enrolled by two different sources: clinicians working at Centers of expertise officially designated to diagnose and care patients with rare diseases and health professionals working in the local health districts. Deaths of patients are monitored by Death Registry. Results So far, 19,547 patients with rare diseases have been registered, and 23% of them are pediatric cases. The overall raw prevalence of the rare diseases monitored in the population under study is 33.09 per 10,000 inhabitants (95% CI 32.56-33.62), whilst the overall incidence is 3.85 per 10,000 inhabitants (95% CI 3.67-4.03). The most commonly-recorded diagnoses belong to the following nosological groups: congenital malformations (Prevalence: 5.45/10,000), hematological diseases (4.83/10,000), ocular disorders (4.47/10,000), diseases of the nervous system (3.51/10,000), and metabolic disorders (2,95/10,000). Most of the deaths in the study population occur among pediatric patients with congenital malformations, and among adult cases with neurological diseases. Rare diseases of the central nervous system carry the highest fatality rate (71.36/1,000). Rare diseases explain 4.2% of general population Years of Life Lost (YLLs), comparing to 1.2% attributable to infectious diseases and 2.6% to diabetes mellitus. Conclusions Our estimates of the burden of rare diseases at population level confirm that these conditions are a relevant public health issue. Our snapshot of their epidemiology

  7. Rare earth niobate coordination polymers

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

    Muniz, Collin N.; Patel, Hiral; Fast, Dylan B.

    Rare-earth (RE) coordination polymers are infinitely tailorable to yield luminescent materials for various applications. In this paper we described the synthesis of a heterometallic rare-earth coordination compound ((CH 3) 2SO) 3(RE)NbO(C 2O 4) 3 ((CH 3) 2SO) = dimethylsulfoxide, DMSO, (C 2O 2 = oxalate), (RE=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb). The structure was obtained from single crystal X-ray diffraction of the La analogue. The Nb =O and DMSO terminal-bonding character guides assembly of an open framework structure with noncentrosymmetric RE-coordination geometry, and large spacing between the RE centers. A second structure was observed by PXRD for themore » smaller rare earths (Dy, Ho, Er, Yb); this structure has not yet been determined. The materials were further characterized using FTIR, and photoluminescence measurements. Characteristic excitation and emission transitions were observed for RE = Nd, Sm, Eu, and Tb. Quantum yield (QY) measurements were performed by exciting Eu and Tb analoges at 394 nm (QY 66%) and 464 nm (QY 71%) for Eu; and 370 nm (QY=40%) for Tb. Finally, we attribute the high QY and bright luminescence to two main structure-function properties of the system; namely the absence of water in the structure, and absence of concentration quenching.« less

  8. Rare earth niobate coordination polymers

    DOE PAGES

    Muniz, Collin N.; Patel, Hiral; Fast, Dylan B.; ...

    2018-01-03

    Rare-earth (RE) coordination polymers are infinitely tailorable to yield luminescent materials for various applications. In this paper we described the synthesis of a heterometallic rare-earth coordination compound ((CH 3) 2SO) 3(RE)NbO(C 2O 4) 3 ((CH 3) 2SO) = dimethylsulfoxide, DMSO, (C 2O 2 = oxalate), (RE=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb). The structure was obtained from single crystal X-ray diffraction of the La analogue. The Nb =O and DMSO terminal-bonding character guides assembly of an open framework structure with noncentrosymmetric RE-coordination geometry, and large spacing between the RE centers. A second structure was observed by PXRD for themore » smaller rare earths (Dy, Ho, Er, Yb); this structure has not yet been determined. The materials were further characterized using FTIR, and photoluminescence measurements. Characteristic excitation and emission transitions were observed for RE = Nd, Sm, Eu, and Tb. Quantum yield (QY) measurements were performed by exciting Eu and Tb analoges at 394 nm (QY 66%) and 464 nm (QY 71%) for Eu; and 370 nm (QY=40%) for Tb. Finally, we attribute the high QY and bright luminescence to two main structure-function properties of the system; namely the absence of water in the structure, and absence of concentration quenching.« less

  9. Rare gases in cyclosilicates and cogenetic minerals

    NASA Technical Reports Server (NTRS)

    Saito, K.; Alexander, E. C., Jr.; Dragon, J. C.; Zashu, S.

    1984-01-01

    The cyclosilicate minerals, beryl, tourmaline, and cordierite, typically contain large amounts of He-4 and Ar-40 which are not in situ radiogenic products. In the study of excess rare gases in cyclosilicates, one of the most enigmatic observations is the age effect, a qualitative tendency for geologically older samples to contain more excess He-4 and Ar-40 than younger samples. The present investigation is concerned with measurements regarding the abundance and isotopic composition of all five rare gases in a number of cyclosilicates as well as in their cogenetic minerals. The significance of the obtained data is discussed. The data indicate that cyclosilicates sample the rare gases present in the environment in which they crystallize. This 'sampling' involves major elemental fractionations which are variable but mineral specific. Cyclosilicates can, therefore, be used to probe the isotopic ratios and elemental compositions.

  10. Rare decays in quark flavour physics

    NASA Astrophysics Data System (ADS)

    Albrecht, Johannes; LHCb Collaboration

    2016-04-01

    Rare heavy-flavour decays are an ideal place to search for the effects of potential new particles that modify the decay rates or the Lorentz structure of the decay vertices. Recent results on Flavour Changing Neutral Current decays from the LHC are reviewed. An emphasis is put on the very rare decay Bs0 →μ+μ-, which was recently observed by the CMS and LHCb experiments, on a recent test of lepton universality in loop processes and on the analysis of the angular distributions of the B0 →K*0μ+μ- decays, both by the LHCb collaboration.

  11. Paratesticular aggressive angiomyxoma: A rare case.

    PubMed

    Ismail, Muhamad Izwan; Wong, Yin Ping; Tan, Guan Hee; Fam, Xeng Inn

    2017-01-01

    Aggressive angiomyxoma (AAM) particularly testicular origin is a rare benign mesenchymal myxoid tumor which is locally aggressive, blatant for local recurrence, and may metastasize. It occurs mostly in females of childbearing age and extremely rare in males. AMM particular testicular origin is not reported in literature yet. This is a 65-year-old man who had a right scrotal swelling. Ultrasound scrotum showed a soft tissue tumor of the right testis. The patient underwent radical right orchidectomy of which histopathologically confirmed to be a paratesticular AAM with clear resection margins. There were no signs of local recurrence or metastasis 2 years postsurgical resection.

  12. New open cluster candidates discovered in the XSTPS-GAC survey

    NASA Astrophysics Data System (ADS)

    Guo, Jin-Cheng; Zhang, Hua-Wei; Zhang, Hui-Hua; Liu, Xiao-Wei; Yuan, Hai-Bo; Huang, Yang; Wang, Song; Chen, Li; Zhao, Hai-Bin; Liu, Ji-Feng; Chen, Bing-Qiu; Xiang, Mao-Sheng; Tian, Zhi-Jia; Huo, Zhi-Ying; Wang, Chun

    2018-03-01

    The Xuyi Schmidt Telescope Photometric Survey of the Galactic Anti-center (XSTPS-GAC) is a photometric sky survey that covers nearly 6000 deg2 towards the Galactic Anti-center (GAC) in the g, r, i bands. Half of its survey field is located on the Galactic Anti-center disk, which makes XSTPS-GAC highly suitable to search for new open clusters in the GAC region. In this paper, we report new open cluster candidates discovered in this survey, as well as properties of these open cluster candidates, such as age, distance and reddening, derived by isochrone fitting in the color-magnitude diagram (CMD). These open cluster candidates are stellar density peaks detected in the star density maps by applying the method from Koposov et al. Each candidate is inspected in terms of its true color image composed from three XSTPS-GAC band images. Then its CMD is checked, in order to identify whether the central region stars have a clear isochrone-like trend differing from background stars. The parameters derived from isochrone fitting for these candidates are mainly based on three band photometry of XSTPS-GAC. Moreover, when these new candidates are able to be seen clearly in 2MASS data, their parameters are also derived based on the 2MASS (J – H, J) CMD. There are a total of 320 known open clusters rediscovered and 24 new open cluster candidates discovered in this work. Furthermore, the parameters of these new candidates, as well as another 11 previously known open clusters, are properly determined for the first time.

  13. Retinal Oximetry Discovers Novel Biomarkers in Retinal and Brain Diseases.

    PubMed

    Stefánsson, Einar; Olafsdottir, Olof Birna; Einarsdottir, Anna Bryndis; Eliasdottir, Thorunn Scheving; Eysteinsson, Thor; Vehmeijer, Wouter; Vandewalle, Evelien; Bek, Toke; Hardarson, Sveinn Hakon

    2017-05-01

    Biomarkers for several eye and brain diseases are reviewed, where retinal oximetry may help confirm diagnosis or measure severity of disease. These include diabetic retinopathy, central retinal vein occlusion (CRVO), retinitis pigmentosa, glaucoma, and Alzheimer's disease. Retinal oximetry is based on spectrophotometric fundus imaging and measures oxygen saturation in retinal arterioles and venules in a noninvasive, quick, safe manner. Retinal oximetry detects changes in oxygen metabolism, including those that result from ischemia or atrophy. In diabetic retinopathy, venous oxygen saturation increases and arteriovenous difference decreases. Both correlate with diabetic retinopathy severity as conventionally classified on fundus photographs. In CRVO, vein occlusion causes hypoxia, which is measured directly by retinal oximetry to confirm the diagnosis and measure severity. In both diseases, the change in oxygen levels is a consequence of disturbed blood flow with resulting tissue hypoxia and vascular endothelial growth factor (VEGF) production. In atrophic diseases, such as retinitis pigmentosa and glaucoma, retinal oxygen consumption is reduced and this is detected by retinal oximetry. Retinal oximetry correlates with visual field damage and retinal atrophy. It is an objective metabolic measure of the degree of retinal atrophy. Finally, the retina is part of the central nervous system tissue and reflects central nervous system diseases. In Alzheimer's disease, a change in retinal oxygen metabolism has been discovered. Retinal oximetry is a novel, noninvasive technology that opens the field of metabolic imaging of the retina. Biomarkers in metabolic, ischemic, and atrophic diseases of the retina and central nervous system have been discovered.

  14. A Scalable Approach for Discovering Conserved Active Subnetworks across Species

    PubMed Central

    Verfaillie, Catherine M.; Hu, Wei-Shou; Myers, Chad L.

    2010-01-01

    Overlaying differential changes in gene expression on protein interaction networks has proven to be a useful approach to interpreting the cell's dynamic response to a changing environment. Despite successes in finding active subnetworks in the context of a single species, the idea of overlaying lists of differentially expressed genes on networks has not yet been extended to support the analysis of multiple species' interaction networks. To address this problem, we designed a scalable, cross-species network search algorithm, neXus (Network - cross(X)-species - Search), that discovers conserved, active subnetworks based on parallel differential expression studies in multiple species. Our approach leverages functional linkage networks, which provide more comprehensive coverage of functional relationships than physical interaction networks by combining heterogeneous types of genomic data. We applied our cross-species approach to identify conserved modules that are differentially active in stem cells relative to differentiated cells based on parallel gene expression studies and functional linkage networks from mouse and human. We find hundreds of conserved active subnetworks enriched for stem cell-associated functions such as cell cycle, DNA repair, and chromatin modification processes. Using a variation of this approach, we also find a number of species-specific networks, which likely reflect mechanisms of stem cell function that have diverged between mouse and human. We assess the statistical significance of the subnetworks by comparing them with subnetworks discovered on random permutations of the differential expression data. We also describe several case examples that illustrate the utility of comparative analysis of active subnetworks. PMID:21170309

  15. Discovering Free Energy Basins for Macromolecular Systems via Guided Multiscale Simulation

    PubMed Central

    Sereda, Yuriy V.; Singharoy, Abhishek B.; Jarrold, Martin F.; Ortoleva, Peter J.

    2012-01-01

    An approach for the automated discovery of low free energy states of macromolecular systems is presented. The method does not involve delineating the entire free energy landscape but proceeds in a sequential free energy minimizing state discovery, i.e., it first discovers one low free energy state and then automatically seeks a distinct neighboring one. These states and the associated ensembles of atomistic configurations are characterized by coarse-grained variables capturing the large-scale structure of the system. A key facet of our approach is the identification of such coarse-grained variables. Evolution of these variables is governed by Langevin dynamics driven by thermal-average forces and mediated by diffusivities, both of which are constructed by an ensemble of short molecular dynamics runs. In the present approach, the thermal-average forces are modified to account for the entropy changes following from our knowledge of the free energy basins already discovered. Such forces guide the system away from the known free energy minima, over free energy barriers, and to a new one. The theory is demonstrated for lactoferrin, known to have multiple energy-minimizing structures. The approach is validated using experimental structures and traditional molecular dynamics. The method can be generalized to enable the interpretation of nanocharacterization data (e.g., ion mobility – mass spectrometry, atomic force microscopy, chemical labeling, and nanopore measurements). PMID:22423635

  16. Macrofaunal communites at newly discovered hydrothermal fields in Central Indian Ridge

    NASA Astrophysics Data System (ADS)

    Miyazaki, J.; Takai, K.; Nakamura, K.; Watanabe, H.; Noguchi, T.; Matsuzaki, T.; Watsuji, T.; Nemoto, S.; Kawagucci, S.; Shibuya, T.; Okamura, K.; Mochizuki, M.; Orihashi, Y.; Marie, D.; Koonjul, M.; Singh, M.; Beedessee, G.; Bhikajee, M.; Tamaki, K.

    2010-12-01

    In YK09-13 Leg1 cruise targeted on the segment 15 and 16 in Central Indian Ridge (CIR), we have successfully discovered two hydrothermal fields, DODO field and Solitaire field. We expected that there were unique macrofaunal communities in these hydrothermal fields, because there was in Kairei field on the segment 1 in CIR. Particularly, a gastropod, “scaly-foot”, which has sclerites covered with iron-sulfide has only discovered in Kairei field. Therefore, it was interesting whether this unique scaly-foot only exists in Kairei fields or widely expands in CIR. In DODO fields, there were 10 to 15 active chimneys. However, very few hydrothermal vent-endemic faunas were observed. We observed only crabs and shrimps but we did not found shells. As opposed to in the Dodo field, biomass and composition of macrofaunal communities were highly prosperous in the Solitaire field, being equal to Kairei field. Although we have an only one dive to explore the Solitaire field, many predominant taxa were sampled and observed, for example, Alviniconcha, mussels, vanacles and so on. However, the most outstanding feature was the presence of a new morphotype of ‘scaly-foot’ gastropod. Discovery of this new-morphytpe ‘scary-foot” disproved our knowledge. In this conference, I will present these observations. Especially characterization of two types of scaly-foot (Kairei-type and Solitaire-type) will be focused.

  17. Combinatorial search of rare-earth free permanent magnets

    NASA Astrophysics Data System (ADS)

    Gao, Tieren; Takeuchi, Ichiro; Fackler, Sean; Fang, Lei; Zhang, Ying; Krammer, Matthew; Anderson, Iver; McCallum, Bill; University of Maryland Collaboration; Ames Laboratory Collaboration

    2013-03-01

    Permanent magnets play important roles in modern technologies such as in generators, motors, speakers, and relays. Today's high performance permanent magnets contain at least one rare earth element such as Nd, Sm, Pr and Dy. However, rare earth elements are increasingly rare and expensive, and alternative permanent magnet materials which do not contain them are needed by the industry. We are using the thin film composition spread technique to explore novel compositions of permanent magnets without rare-earth. Ternary co-sputtering is used to generate composition spreads. We have thus far looked at Mo doped Fe-Co as one of the initial systems to search for possible compounds with enhanced coercive fields. The films were deposited on Si (100) substrates and annealed at different temperatures. The structural properties of films are mapped by synchrotron diffraction. We find that there is a structural transition from a crystalline to an amorphous state at about 20% atomic Mo. With increasing annealing temperature, the Mo onset concentration of the structural transition increases from 25% for 600°C to 35% for 700°C. We find that some of compounds display enhanced coercive field. With increasing Mo concentration, the magnetization of Fe-Co-Mo begins to switch from in-plane to out-of-plane direction. This work is funded by the BREM (Beyond Rare-earth Magnet) project (DOE EERE).

  18. China launched a pilot project to improve its rare disease healthcare levels.

    PubMed

    Cui, Yazhou; Zhou, Xiaoyan; Han, Jinxiang

    2014-01-27

    China is facing the great challenge of serving the world's largest rare disease population. It is necessary to develop a specific medical plan to increase the levels of optimal prevention, diagnosis and treatment of rare diseases under the existing clinical service structures in China. In 2013, China launched its first pilot project focused on 20 representative rare diseases. A national network including approximately 100 provincial or municipal medical centers has been established to enable collaboration on rare diseases across China. The main objectives for this project are to develop and apply medical guidelines and clinical pathways for rare diseases, to establish a rare disease patient registry and data repository system, and to promote molecular testing for rare genetic disorders. This project also emphasizes building close links among the collaborative network, clinicians on the frontlines in basic medical services institutions and rare disease patient organizations. Primarily, this project expects to develop an actionable medical services plan to increase the delivery of quality healthcare for individuals and families living with rare diseases in China within five years.

  19. Post-approval Studies for Rare Disease Treatments and Orphan Drugs.

    PubMed

    Maier, William C; Christensen, Ronald A; Anderson, Patricia

    2017-01-01

    Drug development involves a multi-stage process of drug discovery, animal studies and human clinical trials to assess the safety and efficacy of new medications. Rare disease drug development involves a much smaller number of affected patients, a predominance of pediatric patients and more complicated disease presentation. Post-approval studies are designed to address several limitations associated with the rare disease clinical trials.National and international regulatory agencies in the US and Europe have adopted similar approaches to requirements post-approval data for rare diseases and orphan drug indications. The US FDA published guidance in 2011 and the European Medicines Agency in 2015.Post-approval studies for rare diseases include observational studies, pragmatic trials and randomized controlled studies. Observational studies include both original data collection studies and the use of secondary data (retrospective studies). Original data collection can address limitations of retrospective studies resulting from incomplete information in secondary data sources. Disease registries focus on detail about a broad range of patients with a rare disease while product-related registries focus on specific health care outcomes associated with a single product and may incorporate a comparator of an alternative therapy or therapies.Rare disease patients can be difficult to find and enroll in a registry using conventional physician based driven recruitment. The study process also needs to recognize changes in the patient's disease and lifestyle and adapt both the study design and methods over time. Many rare diseases have strong patient advocacy groups that can in aid the design and execution of rare disease registries.

  20. Rare species support vulnerable functions in high-diversity ecosystems.

    PubMed

    Mouillot, David; Bellwood, David R; Baraloto, Christopher; Chave, Jerome; Galzin, Rene; Harmelin-Vivien, Mireille; Kulbicki, Michel; Lavergne, Sebastien; Lavorel, Sandra; Mouquet, Nicolas; Paine, C E Timothy; Renaud, Julien; Thuiller, Wilfried

    2013-01-01

    Around the world, the human-induced collapses of populations and species have triggered a sixth mass extinction crisis, with rare species often being the first to disappear. Although the role of species diversity in the maintenance of ecosystem processes has been widely investigated, the role of rare species remains controversial. A critical issue is whether common species insure against the loss of functions supported by rare species. This issue is even more critical in species-rich ecosystems where high functional redundancy among species is likely and where it is thus often assumed that ecosystem functioning is buffered against species loss. Here, using extensive datasets of species occurrences and functional traits from three highly diverse ecosystems (846 coral reef fishes, 2,979 alpine plants, and 662 tropical trees), we demonstrate that the most distinct combinations of traits are supported predominantly by rare species both in terms of local abundance and regional occupancy. Moreover, species that have low functional redundancy and are likely to support the most vulnerable functions, with no other species carrying similar combinations of traits, are rarer than expected by chance in all three ecosystems. For instance, 63% and 98% of fish species that are likely to support highly vulnerable functions in coral reef ecosystems are locally and regionally rare, respectively. For alpine plants, 32% and 89% of such species are locally and regionally rare, respectively. Remarkably, 47% of fish species and 55% of tropical tree species that are likely to support highly vulnerable functions have only one individual per sample on average. Our results emphasize the importance of rare species conservation, even in highly diverse ecosystems, which are thought to exhibit high functional redundancy. Rare species offer more than aesthetic, cultural, or taxonomic diversity value; they disproportionately increase the potential breadth of functions provided by ecosystems across