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Sample records for discovery involving devastating

  1. Get Involved in Planetary Discoveries through New Worlds, New Discoveries

    NASA Astrophysics Data System (ADS)

    Shupla, Christine; Shipp, S. S.; Halligan, E.; Dalton, H.; Boonstra, D.; Buxner, S.; SMD Planetary Forum, NASA

    2013-01-01

    "New Worlds, New Discoveries" is a synthesis of NASA’s 50-year exploration history which provides an integrated picture of our new understanding of our solar system. As NASA spacecraft head to and arrive at key locations in our solar system, "New Worlds, New Discoveries" provides an integrated picture of our new understanding of the solar system to educators and the general public! The site combines the amazing discoveries of past NASA planetary missions with the most recent findings of ongoing missions, and connects them to the related planetary science topics. "New Worlds, New Discoveries," which includes the "Year of the Solar System" and the ongoing celebration of the "50 Years of Exploration," includes 20 topics that share thematic solar system educational resources and activities, tied to the national science standards. This online site and ongoing event offers numerous opportunities for the science community - including researchers and education and public outreach professionals - to raise awareness, build excitement, and make connections with educators, students, and the public about planetary science. Visitors to the site will find valuable hands-on science activities, resources and educational materials, as well as the latest news, to engage audiences in planetary science topics and their related mission discoveries. The topics are tied to the big questions of planetary science: how did the Sun’s family of planets and bodies originate and how have they evolved? How did life begin and evolve on Earth, and has it evolved elsewhere in our solar system? Scientists and educators are encouraged to get involved either directly or by sharing "New Worlds, New Discoveries" and its resources with educators, by conducting presentations and events, sharing their resources and events to add to the site, and adding their own public events to the site’s event calendar! Visit to find quality resources and ideas. Connect with

  2. Getting Involved with the Discovery Program

    NASA Technical Reports Server (NTRS)

    Asplund, Shari

    2000-01-01

    NASA's Discovery Program represents the implementation of NASA Administrator Daniel Goldin's vision of 'faster, better, cheaper' planetary missions; encompasses a series of low-cost solar system exploration missions intended to accomplish high quality, focused planetary science investigations using innovative, streamlined, and efficient approaches to assure the highest science value for the cost; and aims to enhance our understanding of the solar system by exploring the planets, their moons and other small bodies, either by traveling to them or remotely from the vicinity of Earth. The objectives of this program include the following: (1) Provide exciting and important scientific data to the global community; (2) Pursue new and innovative ways of doing business; (3) Encourage technological development by designing and testing new technologies and transferring them to the private sector; (4) Increase public awareness of, and appreciation for, solar system exploration through exciting education and public outreach activities; (5) Support national education initiatives through mission-specific programs; and (6) Ensure participation of small disadvantaged businesses, women-owned businesses, HBCUs, and other minority educational institutions in procurements.

  3. Huanglongbing: Devastating disease of citrus

    USDA-ARS?s Scientific Manuscript database

    Citrus greening or Huanglongbing (HLB) disease is devastating the citrus industry worldwide, from Asia to the Americas. The only major citrus regions free of this disease are the Mediterranean and Australia/New Zealand. To date there is no cure, no resistance and no therapy for HLB and production ra...

  4. Recent discoveries and applications involving small-molecule microarrays.

    PubMed

    Hong, Jiyoung A; Neel, Dylan V; Wassaf, Dina; Caballero, Francisco; Koehler, Angela N

    2014-02-01

    High-throughput and unbiased binding assays have proven useful in probe discovery for a myriad of biomolecules, including targets of unknown structure or function and historically challenging target classes. Over the past decade, a number of novel formats for executing large-scale binding assays have been developed and used successfully in probe discovery campaigns. Here we review the use of one such format, the small-molecule microarray (SMM), as a tool for discovering protein-small molecule interactions. This review will briefly highlight selected recent probe discoveries using SMMs as well as novel uses of SMMs in profiling applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Bacteriophage inspired antibiotics discovery against infection involved biofilm.

    PubMed

    Fan, Xiangyu; Li, Wu; Zheng, Fei; Xie, Jianping

    2013-01-01

    Bacterial biofilm profoundly influences the fate of bacteria within and the outcome of related infection, and is closely associated with antibiotics resistance and bacterial persistence. Bacteriophages represent a new promising alternative to combat biofilm-related infection. The interplay between phages and biofilms is complex. Some phages or their components can inhibit the host bacteria biofilm via diverse mechanisms, while other phages can facilitate the host biofilm formation through phage-mediated lysis and extracellular DNA release. In this paper, we summarize the role of bacteriophages in the biofilm formation, and the application of phages to the control of bacterial persisters and infectious biofilms, in particular, the phage-inspired antibiotics discovery.

  6. Discovery.

    ERIC Educational Resources Information Center

    Smithsonian Institution, Washington, DC. National Air And Space Museum.

    This material presents the historical perspectives of flight and student activities for grades K-3 prepared by the National Air and Space Museum (NASM) and National Aeronautics and Space Administration (NASA). Sections included are: (1) "Historical Perspective of Flight"; (2) "Discovery Vocabulary" (listing the terms found in the first section);…

  7. Discovery

    ERIC Educational Resources Information Center

    de Mestre, Neville

    2010-01-01

    All common fractions can be written in decimal form. In this Discovery article, the author suggests that teachers ask their students to calculate the decimals by actually doing the divisions themselves, and later on they can use a calculator to check their answers. This article presents a lesson based on the research of Bolt (1982).

  8. Transcriptome profiling for discovery of genes involved in shoot apical meristem and flower development.

    PubMed

    Singh, Vikash K; Jain, Mukesh

    2014-12-01

    Flower development is one of the major developmental processes that governs seed setting in angiosperms. However, little is known about the molecular mechanisms underlying flower development in legumes. Employing RNA-seq for various stages of flower development and few vegetative tissues in chickpea, we identified differentially expressed genes in flower tissues/stages in comparison to vegetative tissues, which are related to various biological processes and molecular functions during flower development. Here, we provide details of experimental methods, RNA-seq data (available at Gene Expression Omnibus database under GSE42679) and analysis pipeline published by Singh and colleagues in the Plant Biotechnology Journal (Singh et al., 2013), along with additional analysis for discovery of genes involved in shoot apical meristem (SAM) development. Our data provide a resource for exploring the complex molecular mechanisms underlying SAM and flower development and identification of gene targets for functional and applied genomics in legumes.

  9. Recent discoveries concerning the involvement of transcription factors from the Grainyhead-like family in cancer

    PubMed Central

    Mlacki, Michal; Kikulska, Agnieszka; Krzywinska, Ewa; Pawlak, Magdalena

    2015-01-01

    The Grainyhead-like (GRHL) family of transcription factors has three mammalian members, which are currently termed Grainyhead-like 1 (GRHL1), Grainyhead-like 2 (GRHL2), and Grainyhead-like 3 (GRHL3). These factors adopt a DNA-binding immunoglobulin fold homologous to the DNA-binding domain of key tumor suppressor p53. Their patterns of expression are tissue and developmentally specific. Earlier studies of the GRHL proteins focused on their functions in mammalian development. In recent years, these factors have been linked to many different types of cancer: squamous cell carcinoma of the skin, breast cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, clear cell renal cell carcinoma, neuroblastoma, prostate cancer, and cervical cancer. The roles of GRHL proteins in these various types of cancer are complex, and in some cases appear to be contradictory: they can serve to promote cancer development, or they may act as tumor suppressors, depending on the particular GRHL protein involved and on the cancer type. The reasons for obvious discrepancies in results from different studies remain unclear. At the molecular level, the GRHL transcription factors regulate the expression of genes whose products are involved in cellular proliferation, differentiation, adhesion, and polarity. We herein review the roles of GRHL proteins in cancer development, and we critically examine relevant molecular mechanisms, which were proposed by different authors. We also discuss the significance of recent discoveries implicating the involvement of GRHL transcription factors in cancer and highlight potential future applications of this knowledge in cancer treatment. PMID:26069269

  10. Cervicofacial necrotizing fasciitis. A devastating complication of blepharoplasty.

    PubMed

    Ray, A M; Bressler, K; Davis, R E; Gallo, J F; Patete, M L

    1997-06-01

    We report a case of cervicofacial necrotizing fasciitis that developed after blepharoplasty, an occurrence that, to our knowledge, has not previously been reported in the medical literature. A patient who presented to our institution 3 days after undergoing blepharoplasty of the upper eyelid was diagnosed as having fulminant fasciitis involving extensive areas of the face, scalp, and neck. We review the case in detail and discuss clinical and radiological clues to diagnosis, surgical and medical management, wound care, and subsequent scar contracture. This case emphasizes the need for individualized, appropriate postoperative care and for an awareness of this rare, potentially fatal complication. Early recognition and aggressive treatment of cervicofacial fasciitis can arrest its rapid progression and prevent devastating sequelae.

  11. Rheumatoid Vasculitis: A Diminishing Yet Devastating Menace.

    PubMed

    Kishore, Shweta; Maher, Lisa; Majithia, Vikas

    2017-07-01

    Rheumatoid vasculitis (RV) is an unusual complication of long-standing rheumatoid arthritis, which is characterized by the development of necrotizing or leukocytoclastic vasculitis involving small or medium-sized vessels. In this review, we aim to provide an update on the epidemiology, pathogenesis, clinical presentation, and management of this challenging extra-articular manifestation. RV is heterogenous in its clinical presentation depending on the organ and size of blood vessels involved. The most common organs involved are the skin and peripheral nerve. Based on recent population studies, the incidence has significantly decreased with early recognition and the advent of immunosuppressive drugs and biologics; however, the mortality rates remain high. RV remains a serious extra-articular manifestation of RA that needs to be promptly recognized and treated. No consensus is available on treatment, given the ongoing debate of whether the biologics can trigger or treat RV.

  12. Devastating metabolic brain disorders of newborns and young infants.

    PubMed

    Yoon, Hyun Jung; Kim, Ji Hye; Jeon, Tae Yeon; Yoo, So-Young; Eo, Hong

    2014-01-01

    Metabolic disorders of the brain that manifest in the neonatal or early infantile period are usually associated with acute and severe illness and are thus referred to as devastating metabolic disorders. Most of these disorders may be classified as organic acid disorders, amino acid metabolism disorders, primary lactic acidosis, or fatty acid oxidation disorders. Each disorder has distinctive clinical, biochemical, and radiologic features. Early diagnosis is important both for prompt treatment to prevent death or serious sequelae and for genetic counseling. However, diagnosis is often challenging because many findings overlap and may mimic those of more common neonatal conditions, such as hypoxic-ischemic encephalopathy and infection. Ultrasonography (US) may be an initial screening method for the neonatal brain, and magnetic resonance (MR) imaging is the modality of choice for evaluating metabolic brain disorders. Although nonspecific imaging findings are common in early-onset metabolic disorders, characteristic patterns of brain involvement have been described for several disorders. In addition, diffusion-weighted images may be used to characterize edema during an acute episode of encephalopathy, and MR spectroscopy depicts changes in metabolites that may help diagnose metabolic disorders and assess response to treatment. Imaging findings, including those of advanced MR imaging techniques, must be closely reviewed. If one of these rare disorders is suspected, the appropriate biochemical test or analysis of the specific gene should be performed to confirm the diagnosis.

  13. A Multimodal Data Analysis Approach for Targeted Drug Discovery Involving Topological Data Analysis (TDA)

    PubMed Central

    Alagappan, Muthuraman; Jiang, Dadi; Denko, Nicholas

    2017-01-01

    In silico drug discovery refers to a combination of computational techniques that augment our ability to discover drug compounds from compound libraries. Many such techniques exist, including virtual high-throughput screening (vHTS), high-throughput screening (HTS), and mechanisms for data storage and querying. However, presently these tools are often used independent of one another. In this chapter, we describe a new multimodal in silico technique for the hit identification and lead generation phases of traditional drug discovery. Our technique leverages the benefits of three independent methods—virtual high-throughput screening, high-throughput screening, and structural fingerprint analysis—by using a fourth technique called topological data analysis (TDA). We describe how a compound library can be independently tested with vHTS, HTS, and fingerprint analysis, and how the results can be transformed into a topological data analysis network to identify compounds from a diverse group of structural families. This process of using TDA or similar clustering methods to identify drug leads is advantageous because it provides a mechanism for choosing structurally diverse compounds while maintaining the unique advantages of already established techniques such as vHTS and HTS. PMID:27325272

  14. A Multimodal Data Analysis Approach for Targeted Drug Discovery Involving Topological Data Analysis (TDA).

    PubMed

    Alagappan, Muthuraman; Jiang, Dadi; Denko, Nicholas; Koong, Albert C

    In silico drug discovery refers to a combination of computational techniques that augment our ability to discover drug compounds from compound libraries. Many such techniques exist, including virtual high-throughput screening (vHTS), high-throughput screening (HTS), and mechanisms for data storage and querying. However, presently these tools are often used independent of one another. In this chapter, we describe a new multimodal in silico technique for the hit identification and lead generation phases of traditional drug discovery. Our technique leverages the benefits of three independent methods-virtual high-throughput screening, high-throughput screening, and structural fingerprint analysis-by using a fourth technique called topological data analysis (TDA). We describe how a compound library can be independently tested with vHTS, HTS, and fingerprint analysis, and how the results can be transformed into a topological data analysis network to identify compounds from a diverse group of structural families. This process of using TDA or similar clustering methods to identify drug leads is advantageous because it provides a mechanism for choosing structurally diverse compounds while maintaining the unique advantages of already established techniques such as vHTS and HTS.

  15. The Children's War: Their Reactions to Devastating Events.

    ERIC Educational Resources Information Center

    Atwood, Joan D.; Donnelly, Joseph W.

    2002-01-01

    A thorough review of the literature reveals that there is little or no information on children's psychological reactions to devastating events, such as the Oklahoma City bombing, the Gulf War, or the recent destruction of the World Trade Center and the Pentagon. This article explores children's psychological reactions in light of Piagetian theory.…

  16. The Children's War: Their Reactions to Devastating Events.

    ERIC Educational Resources Information Center

    Atwood, Joan D.; Donnelly, Joseph W.

    2002-01-01

    A thorough review of the literature reveals that there is little or no information on children's psychological reactions to devastating events, such as the Oklahoma City bombing, the Gulf War, or the recent destruction of the World Trade Center and the Pentagon. This article explores children's psychological reactions in light of Piagetian theory.…

  17. Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

    PubMed

    Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

    2017-01-22

    The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization.

  18. An Example of Discovery Research Involving the Transfer of Stimulus Control

    ERIC Educational Resources Information Center

    Tiger, Jeffrey H.; Hanley, Gregory P.

    2005-01-01

    The initial purpose of the present study was to replicate procedures for teaching preschool children to recruit attention at appropriate times by having an experimenter signal the availability and unavailability of attention (i.e., arrange a multiple schedule involving reinforcement and extinction; Tiger & Hanley, 2004). Following the development…

  19. Comprehensive transcriptome analysis of Crocus sativus for discovery and expression of genes involved in apocarotenoid biosynthesis.

    PubMed

    Baba, Shoib Ahmad; Mohiuddin, Tabasum; Basu, Swaraj; Swarnkar, Mohit Kumar; Malik, Aubid Hussain; Wani, Zahoor Ahmed; Abbas, Nazia; Singh, Anil Kumar; Ashraf, Nasheeman

    2015-09-15

    Crocus sativus stigmas form rich source of apocarotenoids like crocin, picrocrocin and saffranal which besides imparting color, flavour and aroma to saffron spice also have tremendous pharmacological properties. Inspite of their importance, the biosynthetic pathway of Crocus apocarotenoids is not fully elucidated. Moreover, the mechanism of their stigma specific accumulation remains unknown. Therefore, deep transcriptome sequencing of Crocus stigma and rest of the flower tissue was done to identify the genes and transcriptional regulators involved in the biosynthesis of these compounds. Transcriptome of stigma and rest of the flower tissue was sequenced using Illumina Genome Analyzer IIx platform which generated 64,604,402 flower and 51,350,714 stigma reads. Sequences were assembled de novo using trinity resulting in 64,438 transcripts which were classified into 32,204 unigenes comprising of 9853 clusters and 22,351 singletons. A comprehensive functional annotation and gene ontology (GO) analysis was carried out. 58.5 % of the transcripts showed similarity to sequences present in public databases while rest could be specific to Crocus. 5789 transcripts showed similarity to transcription factors representing 76 families out of which Myb family was most abundant. Many genes involved in carotenoid/apocarotenoid pathway were identified for the first time in this study which includes zeta-carotene isomerase and desaturase, carotenoid isomerase and lycopene epsilon-cyclase. GO analysis showed that the predominant classes in biological process category include metabolic process followed by cellular process and primary metabolic process. KEGG mapping analysis indicated that pathways involved in ribosome, carbon and starch and sucrose metabolism were highly represented. Differential expression analysis indicated that key carotenoid/apocarotenoid pathway genes including phytoene synthase, phytoene desaturase and carotenoid cleavage dioxygenase 2 are enriched in stigma

  20. Discovery of piperonal-converting oxidase involved in the metabolism of a botanical aromatic aldehyde

    PubMed Central

    Doi, Shiori; Hashimoto, Yoshiteru; Tomita, Chiaki; Kumano, Takuto; Kobayashi, Michihiko

    2016-01-01

    Piperonal-catabolizing microorganisms were isolated from soil, the one (strain CT39-3) exhibiting the highest activity being identified as Burkholderia sp. The piperonal-converting enzyme involved in the initial step of piperonal metabolism was purified from strain CT39-3. Gene cloning of the enzyme and a homology search revealed that the enzyme belongs to the xanthine oxidase family, which comprises molybdoenzymes containing a molybdopterin cytosine dinucleotide cofactor. We found that the piperonal-converting enzyme acts on piperonal in the presence of O2, leading to formation of piperonylic acid and H2O2. The growth of strain CT39-3 was inhibited by higher concentrations of piperonal in the culture medium. Together with this finding, the broad substrate specificity of this enzyme for various aldehydes suggests that it would play an important role in the defense mechanism against antimicrobial compounds derived from plant species. PMID:27905507

  1. Cardioproteomics: advancing the discovery of signaling mechanisms involved in cardiovascular diseases

    PubMed Central

    Cui, Ziyou; Dewey, Shannamar; Gomes, Aldrin V

    2011-01-01

    Cardioproteomics (Cardiovascular proteomics) is fast becoming an indispensible technique in deciphering changes in signaling pathways that occur in cardiovascular diseases (CVDs). The quality and availability of the instruments and bioinformatics software used for cardioproteomics continues to improve, and these techniques are now available to most cardiovascular researchers either directly or indirectly via university core centers. The heart and aorta are specialized tissues which present unique challenges to investigate. Currently, the diverse range of proteomic techniques available for cardiovascular research makes the choice of the best method or best combination of methods for the disease parameter(s) being investigated as important as the equipment used. This review focuses on proteomic techniques and their applications which have advanced our understanding of the signaling mechanisms involved in CVDs at the levels of protein complex/protein-protein interaction, post-translational modifications and signaling induced protein changes. PMID:22254205

  2. An example of discovery research involving the transfer of stimulus control.

    PubMed

    Tiger, Jeffrey H; Hanley, Gregory P

    2005-01-01

    The initial purpose of the present study was to replicate procedures for teaching preschool children to recruit attention at appropriate times by having an experimenter signal the availability and unavailability of attention (i.e., arrange a multiple schedule involving reinforcement and extinction; Tiger & Hanley, 2004). Following the development of discriminated social responding, the schedule-correlated stimuli were removed (i.e., a mixed schedule of reinforcement was arranged). However, discriminated responding continued during these conditions. Further evaluation suggested that stimulus control over children's social responding had transferred from the schedule-correlated stimuli to the delivery of reinforcement. The effect of a history of reinforcement under multiple-schedule conditions on performance under mixed schedules was then replicated with 2 participants in a reversal design. These findings suggest that following experience with schedule-correlated stimuli, these stimuli may be removed with only modest disruption to discriminated responding.

  3. An Example of Discovery Research Involving the Transfer of Stimulus Control

    PubMed Central

    2005-01-01

    The initial purpose of the present study was to replicate procedures for teaching preschool children to recruit attention at appropriate times by having an experimenter signal the availability and unavailability of attention (i.e., arrange a multiple schedule involving reinforcement and extinction; Tiger & Hanley, 2004). Following the development of discriminated social responding, the schedule-correlated stimuli were removed (i.e., a mixed schedule of reinforcement was arranged). However, discriminated responding continued during these conditions. Further evaluation suggested that stimulus control over children's social responding had transferred from the schedule-correlated stimuli to the delivery of reinforcement. The effect of a history of reinforcement under multiple-schedule conditions on performance under mixed schedules was then replicated with 2 participants in a reversal design. These findings suggest that following experience with schedule-correlated stimuli, these stimuli may be removed with only modest disruption to discriminated responding. PMID:16463530

  4. Discovery of piperonal-converting oxidase involved in the metabolism of a botanical aromatic aldehyde.

    PubMed

    Doi, Shiori; Hashimoto, Yoshiteru; Tomita, Chiaki; Kumano, Takuto; Kobayashi, Michihiko

    2016-12-01

    Piperonal-catabolizing microorganisms were isolated from soil, the one (strain CT39-3) exhibiting the highest activity being identified as Burkholderia sp. The piperonal-converting enzyme involved in the initial step of piperonal metabolism was purified from strain CT39-3. Gene cloning of the enzyme and a homology search revealed that the enzyme belongs to the xanthine oxidase family, which comprises molybdoenzymes containing a molybdopterin cytosine dinucleotide cofactor. We found that the piperonal-converting enzyme acts on piperonal in the presence of O2, leading to formation of piperonylic acid and H2O2. The growth of strain CT39-3 was inhibited by higher concentrations of piperonal in the culture medium. Together with this finding, the broad substrate specificity of this enzyme for various aldehydes suggests that it would play an important role in the defense mechanism against antimicrobial compounds derived from plant species.

  5. Discovery of genes involved with learning and memory: an experimental synthesis of Hirschian and Benzerian perspectives.

    PubMed

    Tully, T

    1996-11-26

    The biological bases of learning and memory are being revealed today with a wide array of molecular approaches, most of which entail the analysis of dysfunction produced by gene disruptions. This perspective derives both from early "genetic dissections" of learning in mutant Drosophila by Seymour Benzer and colleagues and from earlier behavior-genetic analyses of learning and in Diptera by Jerry Hirsh and coworkers. Three quantitative-genetic insights derived from these latter studies serve as guiding principles for the former. First, interacting polygenes underlie complex traits. Consequently, learning/memory defects associated with single-gene mutants can be quantified accurately only in equilibrated, heterogeneous genetic backgrounds. Second, complex behavioral responses will be composed of genetically distinct functional components. Thus, genetic dissection of complex traits into specific biobehavioral properties is likely. Finally, disruptions of genes involved with learning/memory are likely to have pleiotropic effects. As a result, task-relevant sensorimotor responses required for normal learning must be assessed carefully to interpret performance in learning/memory experiments. In addition, more specific conclusions will be obtained from reverse-genetic experiments, in which gene disruptions are restricted in time and/or space.

  6. A Journey of Self-Discovery: An Intervention Involving Massage, Yoga and Relaxation for Children with Emotional and Behavioural Difficulties Attending Primary Schools

    ERIC Educational Resources Information Center

    Powell, Lesley; Gilchrist, Mollie; Stapley, Jacqueline

    2008-01-01

    This study reports on an intervention involving massage, yoga and relaxation delivered to young children with identified emotional and behavioural difficulties, and at risk of exclusion. Children (n = 126) were invited by the head teacher to participate in the Self-discovery Programme (involving massage, yoga, breath work and relaxation) with…

  7. A Journey of Self-Discovery: An Intervention Involving Massage, Yoga and Relaxation for Children with Emotional and Behavioural Difficulties Attending Primary Schools

    ERIC Educational Resources Information Center

    Powell, Lesley; Gilchrist, Mollie; Stapley, Jacqueline

    2008-01-01

    This study reports on an intervention involving massage, yoga and relaxation delivered to young children with identified emotional and behavioural difficulties, and at risk of exclusion. Children (n = 126) were invited by the head teacher to participate in the Self-discovery Programme (involving massage, yoga, breath work and relaxation) with…

  8. Discovery and Characterization of an Amidinotransferase Involved in the Modification of Archaeal tRNA*♦

    PubMed Central

    Phillips, Gabriela; Chikwana, Vimbai M.; Maxwell, Adrienne; El-Yacoubi, Basma; Swairjo, Manal A.; Iwata-Reuyl, Dirk; de Crécy-Lagard, Valérie

    2010-01-01

    The presence of the 7-deazaguanosine derivative archaeosine (G+) at position 15 in tRNA is one of the diagnostic molecular characteristics of the Archaea. The biosynthesis of this modified nucleoside is especially complex, involving the initial production of 7-cyano-7-deazaguanine (preQ0), an advanced precursor that is produced in a tRNA-independent portion of the biosynthesis, followed by its insertion into the tRNA by the enzyme tRNA-guanine transglycosylase (arcTGT), which replaces the target guanine base yielding preQ0-tRNA. The enzymes responsible for the biosynthesis of preQ0 were recently identified, but the enzyme(s) catalyzing the conversion of preQ0-tRNA to G+-tRNA have remained elusive. Using a comparative genomics approach, we identified a protein family implicated in the late stages of archaeosine biosynthesis. Notably, this family is a paralog of arcTGT and is generally annotated as TgtA2. Structure-based alignments comparing arcTGT and TgtA2 reveal that TgtA2 lacks key arcTGT catalytic residues and contains an additional module. We constructed a Haloferax volcanii ΔtgtA2 derivative and demonstrated that tRNA from this strain lacks G+ and instead accumulates preQ0. We also cloned the corresponding gene from Methanocaldococcus jannaschii (mj1022) and characterized the purified recombinant enzyme. Recombinant MjTgtA2 was shown to convert preQ0-tRNA to G+-tRNA using several nitrogen sources and to do so in an ATP-independent process. This is the only example of the conversion of a nitrile to a formamidine known in biology and represents a new class of amidinotransferase chemistry. PMID:20129918

  9. Discovery and characterization of an amidinotransferase involved in the modification of archaeal tRNA.

    PubMed

    Phillips, Gabriela; Chikwana, Vimbai M; Maxwell, Adrienne; El-Yacoubi, Basma; Swairjo, Manal A; Iwata-Reuyl, Dirk; de Crécy-Lagard, Valérie

    2010-04-23

    The presence of the 7-deazaguanosine derivative archaeosine (G(+)) at position 15 in tRNA is one of the diagnostic molecular characteristics of the Archaea. The biosynthesis of this modified nucleoside is especially complex, involving the initial production of 7-cyano-7-deazaguanine (preQ(0)), an advanced precursor that is produced in a tRNA-independent portion of the biosynthesis, followed by its insertion into the tRNA by the enzyme tRNA-guanine transglycosylase (arcTGT), which replaces the target guanine base yielding preQ(0)-tRNA. The enzymes responsible for the biosynthesis of preQ(0) were recently identified, but the enzyme(s) catalyzing the conversion of preQ(0)-tRNA to G(+)-tRNA have remained elusive. Using a comparative genomics approach, we identified a protein family implicated in the late stages of archaeosine biosynthesis. Notably, this family is a paralog of arcTGT and is generally annotated as TgtA2. Structure-based alignments comparing arcTGT and TgtA2 reveal that TgtA2 lacks key arcTGT catalytic residues and contains an additional module. We constructed a Haloferax volcanii DeltatgtA2 derivative and demonstrated that tRNA from this strain lacks G(+) and instead accumulates preQ(0). We also cloned the corresponding gene from Methanocaldococcus jannaschii (mj1022) and characterized the purified recombinant enzyme. Recombinant MjTgtA2 was shown to convert preQ(0)-tRNA to G(+)-tRNA using several nitrogen sources and to do so in an ATP-independent process. This is the only example of the conversion of a nitrile to a formamidine known in biology and represents a new class of amidinotransferase chemistry.

  10. [Research and development for treating devastating corneal diseases].

    PubMed

    Kinoshita, Shigeru

    2010-03-01

    In order to develop new therapeutic modalities for corneal diseases, it is essential to combine cutting-edge translational research based upon liberal original ideas obtained from clinical experience with state-of-the-art basic science and technology. Here, I describe seven important research projects on which our group has been working. 1. Elucidation of the pathogenesis in gelatinous drop-like corneal dystrophy(GDLD). Due to loss of function of the tumor-associated calcium signal transducer 2 (TACSTD2), a responsible gene for this dystrophy, tight-junction-related proteins cease to function, resulting in severe corneal epithelial barrier impairment. As a result, various proteins contained in tear fluid continuously penetrate into the corneal stroma, promoting the development of massive amyloid deposits. 2. The development of cultivated mucosal epithelial transplantation: A landmark surgery, involving the transplantation of cultivated mucosal epithelial cells from in vitro to in vivo, now recognized as the next generation of ocular surface reconstruction. We began performing cultivated allocorneal epithelial transplantations in 1999, and cultivated auto-corneal and auto-oral mucosal epithelial transplantations in 2002. These proved to be very effective in the reconstruction of both the corneal surface and the conjunctival fornix. 3. Elucidation of the pathogenesis of Stevens-Johnson syndrome: Studies have shown that there is a close relationship between corneal epithelial stem cell loss and the associated degree of visual impairment. We discovered that a steroid pulse therapy at the acute phase aimed at minimizing stem cell loss is very effective in restoring visual acuity. This implies that inhibition of the cytokine storm is essential for the treatment of acute-phase Stevens-Johnson syndrome. The innate immunity abnormality seems to be heavily involved at the onset of this devastating disease. 4. Elucidation of the involvement of EP3 and toll like receptor 3

  11. Prelaminated Gracilis Flap with Buccal Mucosal Graft for Salvage of Devastated Urethra

    PubMed Central

    Nikolavsky, Dmitriy

    2015-01-01

    In patients with devastated bulbous urethra, that is, bulbar necrosis, failed fasciocutaneous repairs and “watering can perineum” repair options are limited by paucity of reliable local tissue suitable for reconstruction. In this case report we demonstrate a novel variation of a two-stage technique for reconstruction of a devastated bulbous urethra in a 57-year-old male who suffered penetrating trauma to his previously reconstructed urethra. Because of extensive loss of local tissue from the prior reconstruction and subsequent trauma and infection a 2-stage technique with use of gracilis was employed. This technique involved creation of two independently vascularized urethral hemi-plates prelaminated with buccal mucosa graft (BMG). In the first stage the dorsal plate was created by quilting buccal graft onto corpora cavernosa to create a temporary augmented perineal urethrostomy. In the same stage the future ventral neourethral plate was created by grafting another BMG onto the exposed distal gracilis muscle. Eight weeks later the two prelaminated plates were anastomosed by tunneling the gracilis-BMG composite into the perineum. At 8-month follow-up patient has normal voiding and continence. To our knowledge this is the first report of reconstructing an entire segment of devastated urethra in such a manner. PMID:26257976

  12. Autonomy in the face of a devastating diagnosis.

    PubMed Central

    Spriggs, M

    1998-01-01

    Literary accounts of traumatic events can be more informative and insightful than personal testimonials. In particular, reference to works of literature can give us a more vivid sense of what it is like to receive a devastating diagnosis. In turn this can lead us to question some common assumptions about the nature of autonomy, particularly for patients in these circumstances. The literature of concentration camp and labour camp experiences can help us understand what it is like to have one's life-plans altered utterly and unexpectedly. Contrary to common views of autonomy which have difficulty in characterising autonomous action when long-standing assumptions are suddenly lost, these examples show that autonomy is possible in these circumstances. We need a theory of autonomy which can deal with traumatic events and is useful in the clinical context. PMID:9603000

  13. A Journey of Self-Discovery: An Intervention Involving Massage, Yoga and Relaxation for Children with Emotional and Behavioural Difficulties Attending Primary Schools

    ERIC Educational Resources Information Center

    Powell, Lesley; Gilchrist, Mollie; Stapley, Jacqueline

    2008-01-01

    This study reports on an intervention involving massage, yoga and relaxation delivered to young children with emotional and behavioural difficulties. Children (n = 126) were invited to participate in the Self-discovery Programme (SDP) with parental consent. A total of 107 children aged 8-11 years completed the SDP and all measures. Children were…

  14. A Journey of Self-Discovery: An Intervention Involving Massage, Yoga and Relaxation for Children with Emotional and Behavioural Difficulties Attending Primary Schools

    ERIC Educational Resources Information Center

    Powell, Lesley; Gilchrist, Mollie; Stapley, Jacqueline

    2008-01-01

    This study reports on an intervention involving massage, yoga and relaxation delivered to young children with emotional and behavioural difficulties. Children (n = 126) were invited to participate in the Self-discovery Programme (SDP) with parental consent. A total of 107 children aged 8-11 years completed the SDP and all measures. Children were…

  15. Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Hepatopancreas of Microbial Challenged Mitten Crab Eriocheir sinensis

    PubMed Central

    Li, Xihong; Cui, Zhaoxia; Liu, Yuan; Song, Chengwen; Shi, Guohui

    2013-01-01

    Background The Chinese mitten crab Eriocheir sinensis is an important economic crustacean and has been seriously attacked by various diseases, which requires more and more information for immune relevant genes on genome background. Recently, high-throughput RNA sequencing (RNA-seq) technology provides a powerful and efficient method for transcript analysis and immune gene discovery. Methods/Principal Findings A cDNA library from hepatopancreas of E. sinensis challenged by a mixture of three pathogen strains (Gram-positive bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia pastoris; 108 cfu·mL−1) was constructed and randomly sequenced using Illumina technique. Totally 39.76 million clean reads were assembled to 70,300 unigenes. After ruling out short-length and low-quality sequences, 52,074 non-redundant unigenes were compared to public databases for homology searching and 17,617 of them showed high similarity to sequences in NCBI non-redundant protein (Nr) database. For function classification and pathway assignment, 18,734 (36.00%) unigenes were categorized to three Gene Ontology (GO) categories, 12,243 (23.51%) were classified to 25 Clusters of Orthologous Groups (COG), and 8,983 (17.25%) were assigned to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Potentially, 24, 14, 47 and 132 unigenes were characterized to be involved in Toll, IMD, JAK-STAT and MAPK pathways, respectively. Conclusions/Significance This is the first systematical transcriptome analysis of components relating to innate immune pathways in E. sinensis. Functional genes and putative pathways identified here will contribute to better understand immune system and prevent various diseases in crab. PMID:23874555

  16. Transcriptome analysis and discovery of genes involved in immune pathways from hepatopancreas of microbial challenged mitten crab Eriocheir sinensis.

    PubMed

    Li, Xihong; Cui, Zhaoxia; Liu, Yuan; Song, Chengwen; Shi, Guohui

    2013-01-01

    The Chinese mitten crab Eriocheir sinensis is an important economic crustacean and has been seriously attacked by various diseases, which requires more and more information for immune relevant genes on genome background. Recently, high-throughput RNA sequencing (RNA-seq) technology provides a powerful and efficient method for transcript analysis and immune gene discovery. A cDNA library from hepatopancreas of E. sinensis challenged by a mixture of three pathogen strains (Gram-positive bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia pastoris; 10(8) cfu·mL(-1)) was constructed and randomly sequenced using Illumina technique. Totally 39.76 million clean reads were assembled to 70,300 unigenes. After ruling out short-length and low-quality sequences, 52,074 non-redundant unigenes were compared to public databases for homology searching and 17,617 of them showed high similarity to sequences in NCBI non-redundant protein (Nr) database. For function classification and pathway assignment, 18,734 (36.00%) unigenes were categorized to three Gene Ontology (GO) categories, 12,243 (23.51%) were classified to 25 Clusters of Orthologous Groups (COG), and 8,983 (17.25%) were assigned to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Potentially, 24, 14, 47 and 132 unigenes were characterized to be involved in Toll, IMD, JAK-STAT and MAPK pathways, respectively. This is the first systematical transcriptome analysis of components relating to innate immune pathways in E. sinensis. Functional genes and putative pathways identified here will contribute to better understand immune system and prevent various diseases in crab.

  17. Encapsulating peritoneal sclerosis—a rare but devastating peritoneal disease

    PubMed Central

    Moinuddin, Zia; Summers, Angela; Van Dellen, David; Augustine, Titus; Herrick, Sarah E.

    2015-01-01

    Encapsulating peritoneal sclerosis (EPS) is a devastating but, fortunately, rare complication of long-term peritoneal dialysis. The disease is associated with extensive thickening and fibrosis of the peritoneum resulting in the formation of a fibrous cocoon encapsulating the bowel leading to intestinal obstruction. The incidence of EPS ranges between 0.7 and 3.3% and increases with duration of peritoneal dialysis therapy. Dialysis fluid is hyperosmotic, hyperglycemic, and acidic causing chronic injury and inflammation in the peritoneum with loss of mesothelium and extensive tissue fibrosis. The pathogenesis of EPS, however, still remains uncertain, although a widely accepted hypothesis is the “two-hit theory,” where, the first hit is chronic peritoneal membrane injury from long standing peritoneal dialysis followed by a second hit such as an episode of peritonitis, genetic predisposition and/or acute cessation of peritoneal dialysis, leading to EPS. Recently, EPS has been reported in patients shortly after transplantation suggesting that this procedure may also act as a possible second insult. The process of epithelial–mesenchymal transition of mesothelial cells is proposed to play a central role in the development of peritoneal sclerosis, a common characteristic of patients on dialysis, however, its importance in EPS is less clear. There is no established treatment for EPS although evidence from small case studies suggests that corticosteroids and tamoxifen may be beneficial. Nutritional support is essential and surgical intervention (peritonectomy and enterolysis) is recommended in later stages to relieve bowel obstruction. PMID:25601836

  18. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.

    PubMed

    Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Del Vecchio, Lucia; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Battaglia, Giovanni Giorgio; Garozzo, Maurizio; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; Pączek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J; Novak, Jan; Julian, Bruce A; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P; Gharavi, Ali G

    2014-11-01

    We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.

  19. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens

    PubMed Central

    Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J.; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Vecchio, Lucia Del; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; Pączek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J.; Novak, Jan; Julian, Bruce A.; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P.; Gharavi, Ali G.

    2014-01-01

    We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six novel genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geo-spatial distribution of risk alleles is highly suggestive of multi-locus adaptation and the genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN. PMID:25305756

  20. Mucormycosis: New Developments into a Persistently Devastating Infection.

    PubMed

    Danion, François; Aguilar, Claire; Catherinot, Emilie; Alanio, Alexandre; DeWolf, Susan; Lortholary, Olivier; Lanternier, Fanny

    2015-10-01

    Mucormycosis is a rare, though increasingly prevalent, life-threatening fungal disease caused by Mucorales. The incidence has increased over the last decade and its mortality remains high at around 50%. Mucormycosis occurs mostly in patients with diabetes mellitus and/or in the context of immunosuppression resulting from chemotherapy for hematological malignancy, hematopoietic stem cell transplantation, or solid-organ transplantation. In this situation, lung and rhino-orbito-cerebral infections are the most frequent localizations of the disease. Prompt initiation of an effective treatment is essential to decrease mortality. However, mucormycosis and aspergillosis share close clinical and radiological features. Invasive procedures such as bronchial endoscopy and/or lung biopsy are necessary to confirm diagnosis, as no indirect tests are yet validated. Therefore, the challenge is to minimize the delay in diagnosis. When present, the reversed halo sign on CT scan is suggestive of mucormycosis. Quantitative polymerase chain reaction is a new promising approach to detect Mucorales DNA in serum and new molecular tools are available to detect Mucorales in tissues as well as to specify species. Recommendations from ECIL and ECMM/ESCMID have recently been published on management of mucormycosis. The recommended treatment is an amphotericin B lipid formulation in combination with surgery and modification of risk factors. High-dose (10 mg/kg) of liposomal amphotericin B is recommended in case of neurological involvement and posaconazole for maintenance therapy. Place of isavuconazole as well as posaconazole new formulations (tablets and intravenous) in first line treatment have to be defined. Improved radiologic descriptions of mucormycosis and new molecular tools may be key elements to help with rapid diagnosis in the future. Clinical trials are warranted to improve therapeutic success and hopefully survival.

  1. An Interactome-Centered Protein Discovery Approach Reveals Novel Components Involved in Mitosome Function and Homeostasis in Giardia lamblia.

    PubMed

    Rout, Samuel; Zumthor, Jon Paulin; Schraner, Elisabeth M; Faso, Carmen; Hehl, Adrian B

    2016-12-01

    Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis. Live cell imaging revealed a highly immobilized array of 30-40 physically distinct mitosome organelles in trophozoites. We provide direct evidence for the single giardial dynamin-related protein as a contributor to mitosomal morphogenesis and homeostasis. To overcome inherent limitations that have hitherto severely hampered the characterization of these unique organelles we applied a novel interaction-based proteome discovery strategy using forward and reverse protein co-immunoprecipitation. This allowed generation of organelle proteome data strictly in a protein-protein interaction context. We built an initial Tom40-centered outer membrane interactome by co-immunoprecipitation experiments, identifying small GTPases, factors with dual mitosome and endoplasmic reticulum (ER) distribution, as well as novel matrix proteins. Through iterative expansion of this protein-protein interaction network, we were able to i) significantly extend this interaction-based mitosomal proteome to include other membrane-associated proteins with possible roles in mitosome morphogenesis and connection to other subcellular compartments, and ii) identify novel matrix proteins which may shed light on mitosome-associated metabolic functions other than Fe-S cluster biogenesis. Functional analysis also revealed conceptual conservation of protein translocation

  2. An Interactome-Centered Protein Discovery Approach Reveals Novel Components Involved in Mitosome Function and Homeostasis in Giardia lamblia

    PubMed Central

    Rout, Samuel; Zumthor, Jon Paulin; Schraner, Elisabeth M.

    2016-01-01

    Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis. Live cell imaging revealed a highly immobilized array of 30–40 physically distinct mitosome organelles in trophozoites. We provide direct evidence for the single giardial dynamin-related protein as a contributor to mitosomal morphogenesis and homeostasis. To overcome inherent limitations that have hitherto severely hampered the characterization of these unique organelles we applied a novel interaction-based proteome discovery strategy using forward and reverse protein co-immunoprecipitation. This allowed generation of organelle proteome data strictly in a protein-protein interaction context. We built an initial Tom40-centered outer membrane interactome by co-immunoprecipitation experiments, identifying small GTPases, factors with dual mitosome and endoplasmic reticulum (ER) distribution, as well as novel matrix proteins. Through iterative expansion of this protein-protein interaction network, we were able to i) significantly extend this interaction-based mitosomal proteome to include other membrane-associated proteins with possible roles in mitosome morphogenesis and connection to other subcellular compartments, and ii) identify novel matrix proteins which may shed light on mitosome-associated metabolic functions other than Fe-S cluster biogenesis. Functional analysis also revealed conceptual conservation of protein translocation

  3. Discovery of a Novel Prolactin in Non-Mammalian Vertebrates: Evolutionary Perspectives and Its Involvement in Teleost Retina Development

    PubMed Central

    Huang, Xigui; Hui, Michelle N. Y.; Liu, Yun; Yuen, Don S. H.; Zhang, Yong; Chan, Wood Yee; Lin, Hao Ran; Cheng, Shuk Han; Cheng, Christopher H. K.

    2009-01-01

    Background The three pituitary hormones, viz. prolactin (PRL), growth hormone (GH) and somatolactin (SL), together with the mammalian placental lactogen (PL), constitute a gene family of hormones with similar gene structure and encoded protein sequences. These hormones are believed to have evolved from a common ancestral gene through several rounds of gene duplication and subsequent divergence. Principal Findings In this study, we have identified a new PRL-like gene in non-mammalian vertebrates through bioinformatics and molecular cloning means. Phylogenetic analyses showed that this novel protein is homologous to the previously identified PRL. A receptor transactivation assay further showed that this novel protein could bind to PRL receptor to trigger the downstream post-receptor event, indicating that it is biologically active. In view of its close phylogenetic relationship with PRL and also its ability to activate PRL receptor, we name it as PRL2 and the previously identified PRL as PRL1. All the newly discovered PRL2 sequences possess three conserved disulfide linkages with the exception of the shark PRL2 which has only two. In sharp contrast to the classical PRL1 which is predominantly expressed in the pituitary, PRL2 was found to be mainly expressed in the eye and brain of the zebrafish but not in the pituitary. A largely reduced inner nuclear layer of the retina was observed after morpholino knockdown of zebrafish PRL2, indicating its role on retina development in teleost. Significance The discovery of this novel PRL has revitalized our understanding on the evolution of the GH/PRL/SL/PL gene family. Its unique expression and functions in the zebrafish eye also provide a new avenue of research on the neuroendocrine control of retina development in vertebrates. PMID:19584915

  4. A facial reconstruction and identification technique for seriously devastating head wounds.

    PubMed

    Joukal, Marek; Frišhons, Jan

    2015-07-01

    Many authors have focused on facial identification techniques, and facial reconstructions for cases when skulls have been found are especially well known. However, a standardized facial identification technique for an unknown body with seriously devastating head injuries has not yet been developed. A reconstruction and identification technique was used in 7 cases of accidents involving trains striking pedestrians. This identification technique is based on the removal of skull bone fragments, subsequent fixation of soft tissue onto a universal commercial polystyrene head model, precise suture of dermatomuscular flaps, and definitive adjustment using cosmetic treatments. After reconstruction, identifying marks such as scars, eyebrows, facial lines, facial hair and partly hairstyle become evident. It is then possible to present a modified picture of the reconstructed face to relatives. After comparing the results with photos of the person before death, this technique has proven to be very useful for identifying unknown bodies when other identification techniques are not available. This technique is useful for its being rather quick and especially for its results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Transcriptome profiling of the testis reveals genes involved in spermatogenesis and marker discovery in the oriental fruit fly, Bactrocera dorsalis.

    PubMed

    Wei, D; Li, H-M; Yang, W-J; Wei, D-D; Dou, W; Huang, Y; Wang, J-J

    2015-02-01

    The testis is a highly specialized tissue that plays a vital role in ensuring fertility by producing spermatozoa, which are transferred to the female during mating. Spermatogenesis is a complex process, resulting in the production of mature sperm, and involves significant structural and biochemical changes in the seminiferous epithelium of the adult testis. The identification of genes involved in spermatogenesis of Bactrocera dorsalis (Hendel) is critical for a better understanding of its reproductive development. In this study, we constructed a cDNA library of testes from male B. dorsalis adults at different ages, and performed de novo transcriptome sequencing to produce a comprehensive transcript data set, using Illumina sequencing technology. The analysis yielded 52 016 732 clean reads, including a total of 4.65 Gb of nucleotides. These reads were assembled into 47 677 contigs (average 443 bp) and then clustered into 30 516 unigenes (average 756 bp). Based on BLAST hits with known proteins in different databases, 20 921 unigenes were annotated with a cut-off E-value of 10(-5). The transcriptome sequences were further annotated using the Clusters of Orthologous Groups, Gene Orthology and the Kyoto Encyclopedia of Genes and Genomes databases. Functional genes involved in spermatogenesis were analysed, including cell cycle proteins, metalloproteins, actin, and ubiquitin and antihyperthermia proteins. Several testis-specific genes were also identified. The transcripts database will help us to understand the molecular mechanisms underlying spermatogenesis in B. dorsalis. Furthermore, 2913 simple sequence repeats and 151 431 single nucleotide polymorphisms were identified, which will be useful for investigating the genetic diversity of B. dorsalis in the future. © 2014 The Royal Entomological Society.

  6. Annotation of genes involved in glycerolipid biosynthesis in Chlamydomonas reinhardtii: discovery of the betaine lipid synthase BTA1Cr.

    PubMed

    Riekhof, Wayne R; Sears, Barbara B; Benning, Christoph

    2005-02-01

    Lipid metabolism in flowering plants has been intensely studied, and knowledge regarding the identities of genes encoding components of the major fatty acid and membrane lipid biosynthetic pathways is very extensive. We now present an in silico analysis of fatty acid and glycerolipid metabolism in an algal model, enabled by the recent availability of expressed sequence tag and genomic sequences of Chlamydomonas reinhardtii. Genes encoding proteins involved in membrane biogenesis were predicted on the basis of similarity to proteins with confirmed functions and were organized so as to reconstruct the major pathways of glycerolipid synthesis in Chlamydomonas. This analysis accounts for the majority of genes predicted to encode enzymes involved in anabolic reactions of membrane lipid biosynthesis and compares and contrasts these pathways in Chlamydomonas and flowering plants. As an important result of the bioinformatics analysis, we identified and isolated the C. reinhardtii BTA1 (BTA1Cr) gene and analyzed the bifunctional protein that it encodes; we predicted this protein to be sufficient for the synthesis of the betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine (DGTS), a major membrane component in Chlamydomonas. Heterologous expression of BTA1Cr led to DGTS accumulation in Escherichia coli, which normally lacks this lipid, and allowed in vitro analysis of the enzymatic properties of BTA1Cr. In contrast, in the bacterium Rhodobacter sphaeroides, two separate proteins, BtaARs and BtaBRs, are required for the biosynthesis of DGTS. Site-directed mutagenesis of the active sites of the two domains of BTA1Cr allowed us to study their activities separately, demonstrating directly their functional homology to the bacterial orthologs BtaARs and BtaBRs.

  7. De novo assembly and discovery of genes that are involved in drought tolerance in Tibetan Sophora moorcroftiana.

    PubMed

    Li, Huie; Yao, Weijie; Fu, Yaru; Li, Shaoke; Guo, Qiqiang

    2015-01-01

    Sophora moorcroftiana, a Leguminosae shrub species that is restricted to the arid and semi-arid regions of the Qinghai-Tibet Plateau, is an ecologically important foundation species and exhibits substantial drought tolerance in the Plateau. There are no functional genomics resources in public databases for understanding the molecular mechanism underlying the drought tolerance of S. moorcroftiana. Therefore, we performed a large-scale transcriptome sequencing of this species under drought stress using the Illumina sequencing technology. A total of 62,348,602 clean reads were obtained. The assembly of the clean reads resulted in 146,943 transcripts, including 66,026 unigenes. In the assembled sequences, 1534 transcription factors were identified and classified into 23 different common families, and 9040 SSR loci, from di- to hexa-nucleotides, whose repeat number is greater than five, were presented. In addition, we performed a gene expression profiling analysis upon dehydration treatment. The results indicated significant differences in the gene expression profiles among the control, mild stress and severe stress. In total, 4687, 5648 and 5735 genes were identified from the comparison of mild versus control, severe versus control and severe versus mild stress, respectively. Based on the differentially expressed genes, a Gene Ontology annotation analysis indicated many dehydration-relevant categories, including 'response to water 'stimulus' and 'response to water deprivation'. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes pathway analysis uncovered some important pathways, such as 'metabolic pathways' and 'plant hormone signal transduction'. In addition, the expression patterns of 25 putative genes that are involved in drought tolerance resulting from quantitative real-time PCR were consistent with their transcript abundance changes as identified by RNA-seq. The globally sequenced genes covered a considerable proportion of the S. moorcroftiana transcriptome

  8. Gene discovery for enzymes involved in limonene modification or utilization by the mountain pine beetle-associated pathogen Grosmannia clavigera.

    PubMed

    Wang, Ye; Lim, Lynette; Madilao, Lina; Lah, Ljerka; Bohlmann, Joerg; Breuil, Colette

    2014-08-01

    To successfully colonize and eventually kill pine trees, Grosmannia clavigera (Gs cryptic species), the main fungal pathogen associated with the mountain pine beetle (Dendroctonus ponderosae), has developed multiple mechanisms to overcome host tree chemical defenses, of which terpenoids are a major component. In addition to a monoterpene efflux system mediated by a recently discovered ABC transporter, Gs has genes that are highly induced by monoterpenes and that encode enzymes that modify or utilize monoterpenes [especially (+)-limonene]. We showed that pine-inhabiting Ophiostomale fungi are tolerant to monoterpenes, but only a few, including Gs, are known to utilize monoterpenes as a carbon source. Gas chromatography-mass spectrometry (GC-MS) revealed that Gs can modify (+)-limonene through various oxygenation pathways, producing carvone, p-mentha-2,8-dienol, perillyl alcohol, and isopiperitenol. It can also degrade (+)-limonene through the C-1-oxygenated pathway, producing limonene-1,2-diol as the most abundant intermediate. Transcriptome sequencing (RNA-seq) data indicated that Gs may utilize limonene 1,2-diol through beta-oxidation and then valine and tricarboxylic acid (TCA) metabolic pathways. The data also suggested that at least two gene clusters, located in genome contigs 108 and 161, were highly induced by monoterpenes and may be involved in monoterpene degradation processes. Further, gene knockouts indicated that limonene degradation required two distinct Baeyer-Villiger monooxygenases (BVMOs), an epoxide hydrolase and an enoyl coenzyme A (enoyl-CoA) hydratase. Our work provides information on enzyme-mediated limonene utilization or modification and a more comprehensive understanding of the interaction between an economically important fungal pathogen and its host's defense chemicals.

  9. Gene Discovery for Enzymes Involved in Limonene Modification or Utilization by the Mountain Pine Beetle-Associated Pathogen Grosmannia clavigera

    PubMed Central

    Wang, Ye; Lim, Lynette; Madilao, Lina; Lah, Ljerka; Bohlmann, Joerg

    2014-01-01

    To successfully colonize and eventually kill pine trees, Grosmannia clavigera (Gs cryptic species), the main fungal pathogen associated with the mountain pine beetle (Dendroctonus ponderosae), has developed multiple mechanisms to overcome host tree chemical defenses, of which terpenoids are a major component. In addition to a monoterpene efflux system mediated by a recently discovered ABC transporter, Gs has genes that are highly induced by monoterpenes and that encode enzymes that modify or utilize monoterpenes [especially (+)-limonene]. We showed that pine-inhabiting Ophiostomale fungi are tolerant to monoterpenes, but only a few, including Gs, are known to utilize monoterpenes as a carbon source. Gas chromatography-mass spectrometry (GC-MS) revealed that Gs can modify (+)-limonene through various oxygenation pathways, producing carvone, p-mentha-2,8-dienol, perillyl alcohol, and isopiperitenol. It can also degrade (+)-limonene through the C-1-oxygenated pathway, producing limonene-1,2-diol as the most abundant intermediate. Transcriptome sequencing (RNA-seq) data indicated that Gs may utilize limonene 1,2-diol through beta-oxidation and then valine and tricarboxylic acid (TCA) metabolic pathways. The data also suggested that at least two gene clusters, located in genome contigs 108 and 161, were highly induced by monoterpenes and may be involved in monoterpene degradation processes. Further, gene knockouts indicated that limonene degradation required two distinct Baeyer-Villiger monooxygenases (BVMOs), an epoxide hydrolase and an enoyl coenzyme A (enoyl-CoA) hydratase. Our work provides information on enzyme-mediated limonene utilization or modification and a more comprehensive understanding of the interaction between an economically important fungal pathogen and its host's defense chemicals. PMID:24837377

  10. A New Golden Age of Natural Products Drug Discovery

    PubMed Central

    Shen, Ben

    2016-01-01

    The 2015 Nobel Prize in Physiology or Medicine has been awarded to William C. Campbell and Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin, respectively, therapies that revolutionized the treatment of devastating parasite diseases. With the recent technological advances, a New Golden Age of natural products drug discovery is dawning. PMID:26638061

  11. A New Golden Age of Natural Products Drug Discovery.

    PubMed

    Shen, Ben

    2015-12-03

    The 2015 Nobel Prize in Physiology or Medicine has been awarded to William C. Campbell, Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin, respectively, therapies that revolutionized the treatment of devastating parasite diseases. With the recent technological advances, a New Golden Age of natural products drug discovery is dawning. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Talking about Twisters: Relations between Mothers' and Children's Contributions to Conversations about a Devastating Tornado

    ERIC Educational Resources Information Center

    Bauer, Patricia J.; Burch, Melissa M.; Van Abbema, Dana L.; Ackil, Jennifer K.

    2007-01-01

    Mother-child dyads who experienced a devastating tornado talked about the storm and about two affectively more positive or neutral events at each of two time points: 4 months and 10 months after the storm. The conversations were analyzed to determine whether mothers and/or children's contributions differed as a function of event type and whether…

  13. Vibrational duetting mimics to trap and disrupt mating of the devastating Asian citrus psyllid insect pest

    USDA-ARS?s Scientific Manuscript database

    The Asian citrus psyllid (ACP) is the primary vector of a bacterium that produces a devastating disease of citrus, huanglongbing. Efficient surveillance of ACP at low population densities is essential for timely pest management programs. ACP males search for mates on tree branches by producing vibra...

  14. Talking about Twisters: Relations between Mothers' and Children's Contributions to Conversations about a Devastating Tornado

    ERIC Educational Resources Information Center

    Bauer, Patricia J.; Burch, Melissa M.; Van Abbema, Dana L.; Ackil, Jennifer K.

    2007-01-01

    Mother-child dyads who experienced a devastating tornado talked about the storm and about two affectively more positive or neutral events at each of two time points: 4 months and 10 months after the storm. The conversations were analyzed to determine whether mothers and/or children's contributions differed as a function of event type and whether…

  15. Guided Discoveries.

    ERIC Educational Resources Information Center

    Ehrlich, Amos

    1991-01-01

    Presented are four mathematical discoveries made by students on an arithmetical function using the Fibonacci sequence. Discussed is the nature of the role of the teacher in directing the students' discovery activities. (KR)

  16. Guided Discoveries.

    ERIC Educational Resources Information Center

    Ehrlich, Amos

    1991-01-01

    Presented are four mathematical discoveries made by students on an arithmetical function using the Fibonacci sequence. Discussed is the nature of the role of the teacher in directing the students' discovery activities. (KR)

  17. End-Cretaceous devastation of terrestrial flora in the boreal Far East

    NASA Astrophysics Data System (ADS)

    Saito, T.; Yamanoi, T.; Kaiho, K.

    1986-09-01

    Terrestrial palynomorphs from the Hokkaido marime sedimentary sequence spanning the Cretaceous/Tertiary (K/T) boundary record sudden changes in the floristic composition at the exact base of the boundary claystone layer; pollen abundance declines that are accompanied by an abrupt rise in the proportion of fern spores are noted to resemble the palynologically defined K/T boundary in the western interior of North America, which coincides with the top of an IR-rich clay layer. The possible synchronous occurrence of analogous floral changes at such widely separated regions implies a devastation of the land flora which although brief was intercontinental in scope, such as a catastrophic meteorite impact.

  18. Second impact syndrome in football: new imaging and insights into a rare and devastating condition.

    PubMed

    Weinstein, Elizabeth; Turner, Michael; Kuzma, Benjamin B; Feuer, Henry

    2013-03-01

    Premature return to play for the concussed pediatric athlete may result in devastating neurological injury. Identification of at-risk patients and ideal management of the concussed athlete remain challenging for the pediatrician. The authors review a case of second impact syndrome in which neuroimaging was obtained between the first and second impacts, a circumstance which to their knowledge has not been previously reported. This case offers new insights into the underlying pathophysiology of this disease process and potential risk factors for its development.

  19. Draft genome of the most devastating insect pest of coffee worldwide: the coffee berry borer, Hypothenemus hampei

    DOE PAGES

    Vega, Fernando E.; Brown, Stuart M.; Chen, Hao; ...

    2015-07-31

    The coffee berry borer, Hypothenemus hampei, is the most economically important insect pest of coffee worldwide. We present an analysis of the draft genome of the coffee berry borer, the third genome for a Coleopteran species. The genome size is ca. 163 Mb with 19,222 predicted protein-coding genes. Analysis was focused on genes involved in primary digestion as well as gene families involved in detoxification of plant defense molecules and insecticides, such as carboxylesterases, cytochrome P450, gluthathione S-transferases, ATP-binding cassette transporters, and a gene that confers resistance to the insecticide dieldrin. A broad range of enzymes capable of degrading complexmore » polysaccharides were identified. We also evaluated the pathogen defense system and found homologs to antimicrobial genes reported in the Drosophila genome. Ten cases of horizontal gene transfer were identified with evidence for expression, integration into the H. hampei genome, and phylogenetic evidence that the sequences are more closely related to bacterial rather than eukaryotic genes. We find the draft genome analysis broadly expands our knowledge on the biology of a devastating tropical insect pest and suggests new pest management strategies.« less

  20. Draft genome of the most devastating insect pest of coffee worldwide: the coffee berry borer, Hypothenemus hampei

    SciTech Connect

    Vega, Fernando E.; Brown, Stuart M.; Chen, Hao; Shen, Eric; Nair, Mridul B.; Ceja-Navarro, Javier A.; Brodie, Eoin L.; Infante, Francisco; Dowd, Patrick F.; Pain, Arnab

    2015-07-31

    The coffee berry borer, Hypothenemus hampei, is the most economically important insect pest of coffee worldwide. We present an analysis of the draft genome of the coffee berry borer, the third genome for a Coleopteran species. The genome size is ca. 163 Mb with 19,222 predicted protein-coding genes. Analysis was focused on genes involved in primary digestion as well as gene families involved in detoxification of plant defense molecules and insecticides, such as carboxylesterases, cytochrome P450, gluthathione S-transferases, ATP-binding cassette transporters, and a gene that confers resistance to the insecticide dieldrin. A broad range of enzymes capable of degrading complex polysaccharides were identified. We also evaluated the pathogen defense system and found homologs to antimicrobial genes reported in the Drosophila genome. Ten cases of horizontal gene transfer were identified with evidence for expression, integration into the H. hampei genome, and phylogenetic evidence that the sequences are more closely related to bacterial rather than eukaryotic genes. We find the draft genome analysis broadly expands our knowledge on the biology of a devastating tropical insect pest and suggests new pest management strategies.

  1. Draft genome of the most devastating insect pest of coffee worldwide: the coffee berry borer, Hypothenemus hampei.

    PubMed

    Vega, Fernando E; Brown, Stuart M; Chen, Hao; Shen, Eric; Nair, Mridul B; Ceja-Navarro, Javier A; Brodie, Eoin L; Infante, Francisco; Dowd, Patrick F; Pain, Arnab

    2015-07-31

    The coffee berry borer, Hypothenemus hampei, is the most economically important insect pest of coffee worldwide. We present an analysis of the draft genome of the coffee berry borer, the third genome for a Coleopteran species. The genome size is ca. 163 Mb with 19,222 predicted protein-coding genes. Analysis was focused on genes involved in primary digestion as well as gene families involved in detoxification of plant defense molecules and insecticides, such as carboxylesterases, cytochrome P450, gluthathione S-transferases, ATP-binding cassette transporters, and a gene that confers resistance to the insecticide dieldrin. A broad range of enzymes capable of degrading complex polysaccharides were identified. We also evaluated the pathogen defense system and found homologs to antimicrobial genes reported in the Drosophila genome. Ten cases of horizontal gene transfer were identified with evidence for expression, integration into the H. hampei genome, and phylogenetic evidence that the sequences are more closely related to bacterial rather than eukaryotic genes. The draft genome analysis broadly expands our knowledge on the biology of a devastating tropical insect pest and suggests new pest management strategies.

  2. Draft genome of the most devastating insect pest of coffee worldwide: the coffee berry borer, Hypothenemus hampei

    PubMed Central

    Vega, Fernando E.; Brown, Stuart M.; Chen, Hao; Shen, Eric; Nair, Mridul B.; Ceja-Navarro, Javier A.; Brodie, Eoin L.; Infante, Francisco; Dowd, Patrick F.; Pain, Arnab

    2015-01-01

    The coffee berry borer, Hypothenemus hampei, is the most economically important insect pest of coffee worldwide. We present an analysis of the draft genome of the coffee berry borer, the third genome for a Coleopteran species. The genome size is ca. 163 Mb with 19,222 predicted protein-coding genes. Analysis was focused on genes involved in primary digestion as well as gene families involved in detoxification of plant defense molecules and insecticides, such as carboxylesterases, cytochrome P450, gluthathione S-transferases, ATP-binding cassette transporters, and a gene that confers resistance to the insecticide dieldrin. A broad range of enzymes capable of degrading complex polysaccharides were identified. We also evaluated the pathogen defense system and found homologs to antimicrobial genes reported in the Drosophila genome. Ten cases of horizontal gene transfer were identified with evidence for expression, integration into the H. hampei genome, and phylogenetic evidence that the sequences are more closely related to bacterial rather than eukaryotic genes. The draft genome analysis broadly expands our knowledge on the biology of a devastating tropical insect pest and suggests new pest management strategies. PMID:26228545

  3. Mental health in Aceh--Indonesia: A decade after the devastating tsunami 2004.

    PubMed

    Marthoenis, Marthoenis; Yessi, Sarifah; Aichberger, Marion C; Schouler-Ocak, Meryam

    2016-02-01

    The province of Aceh has suffered enormously from the perennial armed conflict and the devastating Tsunami in 2004. Despite the waves of external aid and national concern geared toward improving healthcare services as part of the reconstruction and rehabilitation efforts after the Tsunami, mental health services still require much attention. This paper aims to understand the mental healthcare system in Aceh Province, Indonesia; its main focus is on the burden, on the healthcare system, its development, service delivery and cultural issues from the devastating Tsunami in 2004 until the present. We reviewed those published and unpublished reports from the local and national government, from international instances (UN bodies, NGOs) and from the academic literature pertaining to mental health related programs conducted in Aceh. To some extent, mental health services in Aceh have been improved compared to their condition before the Tsunami. The development programs have focused on procurement of policy, improvement of human resources, and enhancing service delivery. Culture and religious beliefs shape the pathways by which people seek mental health treatment. The political system also determines the development of the mental health service in the province. The case of Aceh is a unique example where conflict and disaster serve as the catalysts toward the development of a mental healthcare system. Several factors contribute to the improvement of the mental health system, but security is a must. Whilst the Acehnese enjoy the improvements, some issues such as stigma, access to care and political fluctuations remain challenging. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. The Greatest Mathematical Discovery?

    SciTech Connect

    Bailey, David H.; Borwein, Jonathan M.

    2010-05-12

    What mathematical discovery more than 1500 years ago: (1) Is one of the greatest, if not the greatest, single discovery in the field of mathematics? (2) Involved three subtle ideas that eluded the greatest minds of antiquity, even geniuses such as Archimedes? (3) Was fiercely resisted in Europe for hundreds of years after its discovery? (4) Even today, in historical treatments of mathematics, is often dismissed with scant mention, or else is ascribed to the wrong source? Answer: Our modern system of positional decimal notation with zero, together with the basic arithmetic computational schemes, which were discovered in India about 500 CE.

  5. A submarine landslide source for the devastating 1964 Chenega tsunami, southern Alaska

    USGS Publications Warehouse

    Brothers, Daniel; Haeussler, Peter J.; Lee Liberty,; David Finlayson,; Geist, Eric L.; Labay, Keith A.; Michael Byerly,

    2016-01-01

    During the 1964 Great Alaska earthquake (Mw 9.2), several fjords, straits, and bays throughout southern Alaska experienced significant tsunami runup of localized, but unexplained origin. Dangerous Passage is a glacimarine fjord in western Prince William Sound, which experienced a tsunami that devastated the village of Chenega where 23 of 75 inhabitants were lost – the highest relative loss of any community during the earthquake. Previous studies suggested the source of the devastating tsunami was either from a local submarine landslide of unknown origin or from coseismic tectonic displacement. Here we present new observations from high-resolution multibeam bathymetry and seismic reflection surveys conducted in the waters adjacent to the village of Chenega. The seabed morphology and substrate architecture reveal a large submarine landslide complex in water depths of 120–360 m. Analysis of bathymetric change between 1957 and 2014 indicates the upper 20–50 m (∼0.7 km3) of glacimarine sediment was destabilized and evacuated from the steep face of a submerged moraine and an adjacent ∼21 km2 perched sedimentary basin. Once mobilized, landslide debris poured over the steep, 130 m-high face of a deeper moraine and then blanketed the terminal basin (∼465 m water depth) in 11 ± 5 m of sediment. These results, combined with inverse tsunami travel-time modeling, suggest that earthquake- triggered submarine landslides generated the tsunami that struck the village of Chenega roughly 4 min after shaking began. Unlike other tsunamigenic landslides observed in and around Prince William Sound in 1964, the failures in Dangerous Passage are not linked to an active submarine delta. The requisite environmental conditions needed to generate large submarine landslides in glacimarine fjords around the world may be more common than previously thought. 

  6. A submarine landslide source for the devastating 1964 Chenega tsunami, southern Alaska

    NASA Astrophysics Data System (ADS)

    Brothers, Daniel S.; Haeussler, Peter J.; Liberty, Lee; Finlayson, David; Geist, Eric; Labay, Keith; Byerly, Mike

    2016-03-01

    During the 1964 Great Alaska earthquake (Mw 9.2), several fjords, straits, and bays throughout southern Alaska experienced significant tsunami runup of localized, but unexplained origin. Dangerous Passage is a glacimarine fjord in western Prince William Sound, which experienced a tsunami that devastated the village of Chenega where 23 of 75 inhabitants were lost - the highest relative loss of any community during the earthquake. Previous studies suggested the source of the devastating tsunami was either from a local submarine landslide of unknown origin or from coseismic tectonic displacement. Here we present new observations from high-resolution multibeam bathymetry and seismic reflection surveys conducted in the waters adjacent to the village of Chenega. The seabed morphology and substrate architecture reveal a large submarine landslide complex in water depths of 120-360 m. Analysis of bathymetric change between 1957 and 2014 indicates the upper 20-50 m (∼0.7 km3) of glacimarine sediment was destabilized and evacuated from the steep face of a submerged moraine and an adjacent ∼21 km2 perched sedimentary basin. Once mobilized, landslide debris poured over the steep, 130 m-high face of a deeper moraine and then blanketed the terminal basin (∼465 m water depth) in 11 ± 5 m of sediment. These results, combined with inverse tsunami travel-time modeling, suggest that earthquake-triggered submarine landslides generated the tsunami that struck the village of Chenega roughly 4 min after shaking began. Unlike other tsunamigenic landslides observed in and around Prince William Sound in 1964, the failures in Dangerous Passage are not linked to an active submarine delta. The requisite environmental conditions needed to generate large submarine landslides in glacimarine fjords around the world may be more common than previously thought.

  7. Comparative genomics guided discovery of two missing archaeal enzyme families involved in the biosynthesis of the pterin moiety of tetrahydromethanopterin and tetrahydrofolate.

    PubMed

    de Crécy-Lagard, Valérie; Phillips, Gabriela; Grochowski, Laura L; El Yacoubi, Basma; Jenney, Francis; Adams, Michael W W; Murzin, Alexey G; White, Robert H

    2012-11-16

    C-1 carriers are essential cofactors in all domains of life, and in Archaea, these can be derivatives of tetrahydromethanopterin (H(4)-MPT) or tetrahydrofolate (H(4)-folate). Their synthesis requires 6-hydroxymethyl-7,8-dihydropterin diphosphate (6-HMDP) as the precursor, but the nature of pathways that lead to its formation were unknown until the recent discovery of the GTP cyclohydrolase IB/MptA family that catalyzes the first step, the conversion of GTP to dihydroneopterin 2',3'-cyclic phosphate or 7,8-dihydroneopterin triphosphate [El Yacoubi, B.; et al. (2006) J. Biol. Chem., 281, 37586-37593 and Grochowski, L. L.; et al. (2007) Biochemistry46, 6658-6667]. Using a combination of comparative genomics analyses, heterologous complementation tests, and in vitro assays, we show that the archaeal protein families COG2098 and COG1634 specify two of the missing 6-HMDP synthesis enzymes. Members of the COG2098 family catalyze the formation of 6-hydroxymethyl-7,8-dihydropterin from 7,8-dihydroneopterin, while members of the COG1634 family catalyze the formation of 6-HMDP from 6-hydroxymethyl-7,8-dihydropterin. The discovery of these missing genes solves a long-standing mystery and provides novel examples of convergent evolutions where proteins of dissimilar architectures perform the same biochemical function.

  8. Liberating Discoveries.

    PubMed

    Bunkers, Sandra Schmidt

    2017-07-01

    The author in this article identifies two liberating discoveries that foster human flourishing: the potential of new knowledge and the importance of living gratitude. These two liberating discoveries are explored from the humanbecoming perspective and cite important inquiries that expand understanding of the phenomena of new knowledge and feeling grateful.

  9. Recent developments in drug discovery against the protozoal parasites Cryptosporidium and Toxoplasma.

    PubMed

    Chellan, Prinessa; Sadler, Peter J; Land, Kirkwood M

    2017-04-01

    Apicomplexan parasites cause some of the most devastating human diseases, including malaria, toxoplasmosis, and cryptosporidiosis. New drug discovery is imperative in light of increased resistance. In this digest article, we briefly explore some of the recent and promising developments in new drug discovery against two apicomplexan parasites, Cryptosporidium and Toxoplasma.

  10. The emergence of devastating impulse control disorders during dopamine agonist therapy of the restless legs syndrome.

    PubMed

    Dang, Dien; Cunnington, David; Swieca, John

    2011-01-01

    The Restless Legs Syndrome is a common sensorimotor disorder, typically amenable to treatment with dopamine agonist therapy. Dopamine agonists have been associated with emergent impulse control disorders (ICDs) when used in patients with Parkinson disease, and ICDs have now been reported in individuals with RLS on dopamine agonist therapy. Our aim was to characterize cases of emergent ICDs in Australian patients with focus on the dopamine agonists implicated and the social significance of ICDs. A series of RLS patients on dopamine agonist therapy were identified with ICDs over a 2-year period. Additional cases of ICDs were found using a mailout questionnaire designed to capture those with high impulsivity. These patients were assessed using the Barratt Impulsiveness Scale, Version 11, and a modified Minnesota Impulse Disorders Interview. Case records and medication schedules were evaluated. Twelve cases of patients with de novo ICDs were found with a range of impulsive behaviors including pathological gambling, kleptomania, compulsive shopping, and hypersexuality. Criminality, suicidality, and marital discord also were featured. These occurred over a wide range of latencies and l-dopa exposures. This group of Australian RLS patients with ICDs display high levels of impulsivity and is the first to use the BIS-11 questionnaire in this setting. Impulse control disorders can occur over a wide range of dopamine agonist therapy types and dose exposures. Impulse control disorder tendencies may persist, despite withdrawal of dopamine agonists. The emergence of ICDs needs careful consideration in light of their potentially devastating financial, social, and marital consequences.

  11. Devastating Transboundary Impacts of Sea Star Wasting Disease on Subtidal Asteroids.

    PubMed

    Montecino-Latorre, Diego; Eisenlord, Morgan E; Turner, Margaret; Yoshioka, Reyn; Harvell, C Drew; Pattengill-Semmens, Christy V; Nichols, Janna D; Gaydos, Joseph K

    2016-01-01

    Sea star wasting disease devastated intertidal sea star populations from Mexico to Alaska between 2013-15, but little detail is known about its impacts to subtidal species. We assessed the impacts of sea star wasting disease in the Salish Sea, a Canadian / United States transboundary marine ecosystem, and world-wide hotspot for temperate asteroid species diversity with a high degree of endemism. We analyzed roving diver survey data for the three most common subtidal sea star species collected by trained volunteer scuba divers between 2006-15 in 5 basins and on the outer coast of Washington, as well as scientific strip transect data for 11 common subtidal asteroid taxa collected by scientific divers in the San Juan Islands during the spring/summer of 2014 and 2015. Our findings highlight differential susceptibility and impact of sea star wasting disease among asteroid species populations and lack of differences between basins or on Washington's outer coast. Specifically, severe depletion of sunflower sea stars (Pycnopodia helianthoides) in the Salish Sea support reports of major declines in this species from California to Alaska, raising concern for the conservation of this ecologically important subtidal predator.

  12. Psychological distress in an earthquake-devastated area with pre-existing high rate of suicide.

    PubMed

    Tachibana, Akira; Kitamura, Hideaki; Shindo, Masanobu; Honma, Hiroko; Someya, Toshiyuki

    2014-10-30

    On 12 March 2011 an earthquake devastated the Matsunoyama and Matsudai districts of Tōkamachi City, Niigata, Japan. These areas had high pre-existing suicide rates, especially among the elderly. We investigated whether mental health status became worse among the sufferers 5 months after the earthquake, and what kind of factors were implicated in any changes. A 15-item questionnaire that tapped earthquake-related variables and the Kessler 10 Psychological Distress Scale to measure psychological distress were distributed to 1923 residents aged over 40 years. The mean age (S.D.) of the total 1731 respondents (male, 805; female, 926) was 68.2 (13.1) years. Of these, we assessed K10 scores from 1346 respondents. The mean scores (S.D.) for K10 and K6 (six selected items from the K10) were 5.8 (6.3) and 3.4 (3.9), respectively. Among the respondents, 9.1% and 3.2% obtained a score of K10 ≥15 and K6 ≥13, respectively. These scores showed slightly higher psychological distress, especially among the elderly, in comparison with existing community-based data. Categorical regression analysis revealed significant and relatively strong effects of initial psychological impact, decrease in sleep hours, advanced age, and decrease in interpersonal relationships within the community on the K10 score. The last item suggests the importance of socio-environmental factors in post-disaster mental health.

  13. Earth observation data based rapid flood-extent modelling for tsunami-devastated coastal areas

    NASA Astrophysics Data System (ADS)

    Hese, Sören; Heyer, Thomas

    2016-04-01

    Earth observation (EO)-based mapping and analysis of natural hazards plays a critical role in various aspects of post-disaster aid management. Spatial very high-resolution Earth observation data provide important information for managing post-tsunami activities on devastated land and monitoring re-cultivation and reconstruction. The automatic and fast use of high-resolution EO data for rapid mapping is, however, complicated by high spectral variability in densely populated urban areas and unpredictable textural and spectral land-surface changes. The present paper presents the results of the SENDAI project, which developed an automatic post-tsunami flood-extent modelling concept using RapidEye multispectral satellite data and ASTER Global Digital Elevation Model Version 2 (GDEM V2) data of the eastern coast of Japan (captured after the Tohoku earthquake). In this paper, the authors developed both a bathtub-modelling approach and a cost-distance approach, and integrated the roughness parameters of different land-use types to increase the accuracy of flood-extent modelling. Overall, the accuracy of the developed models reached 87-92%, depending on the analysed test site. The flood-modelling approach was explained and results were compared with published approaches. We came to the conclusion that the cost-factor-based approach reaches accuracy comparable to published results from hydrological modelling. However the proposed cost-factor approach is based on a much simpler dataset, which is available globally.

  14. Devastating Transboundary Impacts of Sea Star Wasting Disease on Subtidal Asteroids

    PubMed Central

    Montecino-Latorre, Diego; Eisenlord, Morgan E.; Turner, Margaret; Yoshioka, Reyn; Harvell, C. Drew; Pattengill-Semmens, Christy V.; Nichols, Janna D.

    2016-01-01

    Sea star wasting disease devastated intertidal sea star populations from Mexico to Alaska between 2013–15, but little detail is known about its impacts to subtidal species. We assessed the impacts of sea star wasting disease in the Salish Sea, a Canadian / United States transboundary marine ecosystem, and world-wide hotspot for temperate asteroid species diversity with a high degree of endemism. We analyzed roving diver survey data for the three most common subtidal sea star species collected by trained volunteer scuba divers between 2006–15 in 5 basins and on the outer coast of Washington, as well as scientific strip transect data for 11 common subtidal asteroid taxa collected by scientific divers in the San Juan Islands during the spring/summer of 2014 and 2015. Our findings highlight differential susceptibility and impact of sea star wasting disease among asteroid species populations and lack of differences between basins or on Washington’s outer coast. Specifically, severe depletion of sunflower sea stars (Pycnopodia helianthoides) in the Salish Sea support reports of major declines in this species from California to Alaska, raising concern for the conservation of this ecologically important subtidal predator. PMID:27783620

  15. Management of the devastated posterior urethra and bladder neck: refractory incontinence and stenosis.

    PubMed

    Anderson, Kirk M; Higuchi, Ty T; Flynn, Brian J

    2015-02-01

    Stricture of the proximal urethra following treatment for prostate cancer occurs in an estimated 1-8% of patients. Following prostatectomy, urethral reconstruction is feasible in many patients. However, in those patients with prior radiation therapy (RT), failed reconstruction, refractory incontinence or multiple comorbidities, reconstruction may not be feasible. The purpose of this article is to review the evaluation and management options for patients who are not candidates for reconstruction of the posterior urethra and require urinary diversion. Patient evaluation should result in the decision whether reconstruction is feasible. In our experience, risk factors for failed reconstruction include prior radiation and multiple failed endoscopic treatments. Pre-operative cystoscopy is an essential part of the evaluations to identify tissue necrosis, dystrophic calcification, or tumor in the urethra, prostate and/or bladder. If urethral reconstruction is not feasible it is imperative to discuss options for urine diversion with the patient. Treatment options include simple catheter diversion, urethral ligation, and both bladder preserving and non-preserving diversion. Surgical management should address both the bladder and the bladder outlet. This can be accomplished from a perineal, abdominal or abdomino-perineal approach. The devastated bladder outlet is a challenging problem to treat. Typically, patients undergo multiple procedures in an attempt to restore urethral continuity and continence. For the small subset who fails reconstruction, urinary diversion provides a definitive, "end-stage" treatment resulting in improved quality of life.

  16. The role of fabricated chimeric free flaps in reconstruction of devastating hand and forearm injuries.

    PubMed

    Giessler, Goetz A; Schmidt, Andreas B; Germann, Guenter; Pelzer, Michael

    2011-11-01

    Devastating hand and forearm injuries almost exclusively need free flap transfer if reconstruction is attempted. Early active and passive motion is only possible with aggressive, early, and comprehensive reconstruction. Despite recent advances in compound flaps, in selected cases it might be wise to harvest several smaller flaps and microsurgically combine them to one "chain-linked" flap "system." Four microsurgically fabricated chimeric free flaps were used in four patients for complex hand and forearm injuries. The combinations were sensate anterolateral thigh (ALT) flap plus sensate extended lateral arm flap (2x), ALT plus free fibula, and ALT plus functional musculocutaneous gracilis muscle. All flaps survived completely. Functional rehabilitation was possible immediately after flap transfer. There were no donor-site complications except two widened scars. The microsurgical fabrication of chimeric free flaps, as well established in head and neck reconstruction, can be successfully adapted to massive hand injuries as well. Individual placement of selected tissue components, early comprehensive reconstruction, and reduction of the number of operations are beneficial in cases that need more than one free flap.

  17. Hybridization and polyploidy enable genomic plasticity without sex in the most devastating plant-parasitic nematodes

    PubMed Central

    Perfus-Barbeoch, Laetitia; Da Rocha, Martine; Sallet, Erika; Bailly-Bechet, Marc; Castagnone-Sereno, Philippe; Flot, Jean-François; Kozlowski, Djampa K.; Cazareth, Julie; Couloux, Arnaud; Da Silva, Corinne; Guy, Julie; Kim-Jo, Yu-Jin; Rancurel, Corinne; Abad, Pierre; Wincker, Patrick

    2017-01-01

    Root-knot nematodes (genus Meloidogyne) exhibit a diversity of reproductive modes ranging from obligatory sexual to fully asexual reproduction. Intriguingly, the most widespread and devastating species to global agriculture are those that reproduce asexually, without meiosis. To disentangle this surprising parasitic success despite the absence of sex and genetic exchanges, we have sequenced and assembled the genomes of three obligatory ameiotic and asexual Meloidogyne. We have compared them to those of relatives able to perform meiosis and sexual reproduction. We show that the genomes of ameiotic asexual Meloidogyne are large, polyploid and made of duplicated regions with a high within-species average nucleotide divergence of ~8%. Phylogenomic analysis of the genes present in these duplicated regions suggests that they originated from multiple hybridization events and are thus homoeologs. We found that up to 22% of homoeologous gene pairs were under positive selection and these genes covered a wide spectrum of predicted functional categories. To biologically assess functional divergence, we compared expression patterns of homoeologous gene pairs across developmental life stages using an RNAseq approach in the most economically important asexually-reproducing nematode. We showed that >60% of homoeologous gene pairs display diverged expression patterns. These results suggest a substantial functional impact of the genome structure. Contrasting with high within-species nuclear genome divergence, mitochondrial genome divergence between the three ameiotic asexuals was very low, signifying that these putative hybrids share a recent common maternal ancestor. Transposable elements (TE) cover a ~1.7 times higher proportion of the genomes of the ameiotic asexual Meloidogyne compared to the sexual relative and might also participate in their plasticity. The intriguing parasitic success of asexually-reproducing Meloidogyne species could be partly explained by their TE

  18. Bacterial Symbionts of a Devastating Coffee Plant Pest, the Stinkbug Antestiopsis thunbergii (Hemiptera: Pentatomidae)

    PubMed Central

    Matsuura, Yu; Hosokawa, Takahiro; Serracin, Mario; Tulgetske, Genet M.; Miller, Thomas A.

    2014-01-01

    Stinkbugs of the genus Antestiopsis, so-called antestia bugs or variegated coffee bugs, are notorious pests of coffee plants in Africa. We investigated the symbiotic bacteria associated with Antestiopsis thunbergii, a major coffee plant pest in Rwanda. PCR, cloning, sequencing, and phylogenetic analysis of bacterial genes identified four distinct bacterial lineages associated with A. thunbergii: a gammaproteobacterial gut symbiont and symbionts representing the genera Sodalis, Spiroplasma, and Rickettsia. In situ hybridization showed that the gut symbiont densely occupied the lumen of midgut crypts, whereas the Sodalis symbiont, the Spiroplasma symbiont, and the Rickettsia symbiont sparsely and sporadically infected various cells and tissues. Diagnostic PCR survey of 154 A. thunbergii individuals collected at 8 localities in Rwanda revealed high infection frequencies (100% for the gut symbiont, 51.3% for the Sodalis symbiont, 52.6% for the Spiroplasma symbiont, and 24.0% for the Rickettsia symbiont). These results suggest that the gut symbiont is the primary symbiotic associate of obligate nature for A. thunbergii, whereas the Sodalis symbiont, the Spiroplasma symbiont, and the Rickettsia symbiont are the secondary symbiotic associates of facultative nature. We observed high coinfection frequencies, i.e., 7.8% of individuals with quadruple infection with all the symbionts, 32.5% with triple infections with the gut symbiont and two of the secondary symbionts, and 39.6% with double infections with the gut symbiont and any of the three secondary symbionts, which were statistically not different from the expected coinfection frequencies and probably reflected random associations. The knowledge of symbiotic microbiota in A. thunbergii will provide useful background information for controlling this devastating coffee plant pest. PMID:24727277

  19. Cystectomy and Urinary Diversion for the Management of a Devastated Lower Urinary Tract Following Prostatic Cryotherapy and/or Radiotherapy.

    PubMed

    Sack, Bryan S; Langenstroer, Peter; Guralnick, Michael L; Jacobsohn, Kenneth M; O'Connor, R Corey

    2016-04-01

    We investigated the outcomes and quality of life measures in men who underwent cystectomy and urinary diversion for devastating lower urinary tract toxicity after prostatic radiotherapy and/or cryotherapy for the treatment of prostate cancer. Records of patients who underwent cystectomy and urinary diversion for the management of a devastated lower urinary tract following prostatic radiotherapy or cryotherapy were reviewed retrospectively. A postoperative, retrospective quality of life (QOL) survey was designed specific to this patient subset and obtained by telephone interview. Extirpative surgery with urinary diversion for management of a devastated lower urinary tract was performed on 15 patients with a mean age of 72 years (range 63-82). Toxicities leading to bladder removal included bladder neck contractures, prostatic necrosis, incontinence, osteomyelitis, bladder calculi, fistulae, urethral strictures, abscesses, necrotizing fasciitis, and radiation/hemorrhagic cystitis. The mean number of failed conservative, minimally invasive interventions per patients prior to cystectomy was 3.7 (range 1-12). The average time period from major complication following radiotherapy/cryotherapy to cystectomy was 29.1 months (range 5-65). The QOL survey showed all of the patients who completed the survey (n = 13) would undergo the procedure again and 11 (85%) would have undergone the procedure an average of 13.2 months sooner (range 5-36). Toxicities secondary to prostatic radiotherapy or cryotherapy may be debilitating. Our results demonstrate that cystectomy with urinary diversion can improve QOL in patients with a devastated lower urinary tract.

  20. Discovery of genes involved in mitosis, cell division, cell wall integrity and chromosome segregation through construction of Schizosaccharomyces pombe deletion strains

    PubMed Central

    Chen, Jun-Song; Beckley, Janel R.; Ren, Liping; Feoktistova, Anna; Jensen, Michael A.; Rhind, Nick; Gould, Kathleen L.

    2016-01-01

    The fission yeast model system Schizosaccharomyces pombe is used to study fundamental biological processes. To continue to fill gaps in the S. pombe gene deletion collection, we constructed a set of 90 haploid gene deletion strains covering many previously uncharacterized genes. To begin to understand the function of these genes, we exposed this collection of strains to a battery of stress conditions. Using this information in combination with microscopy, proteomics and mini-chromosome loss assays, we identified genes involved in cell wall integrity, cytokinesis, chromosome segregation and DNA metabolism. This subset of nonessential gene deletions will add to the toolkits available for the study of biological processes in S. pombe. PMID:27168121

  1. Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Coelomocytes of Sea Cucumber (Apostichopus japonicus) after Vibrio splendidus Challenge.

    PubMed

    Gao, Qiong; Liao, Meijie; Wang, Yingeng; Li, Bin; Zhang, Zheng; Rong, Xiaojun; Chen, Guiping; Wang, Lan

    2015-07-17

    Vibrio splendidus is identified as one of the major pathogenic factors for the skin ulceration syndrome in sea cucumber (Apostichopus japonicus), which has vastly limited the development of the sea cucumber culture industry. In order to screen the immune genes involving Vibrio splendidus challenge in sea cucumber and explore the molecular mechanism of this process, the related transcriptome and gene expression profiling of resistant and susceptible biotypes of sea cucumber with Vibrio splendidus challenge were collected for analysis. A total of 319,455,942 trimmed reads were obtained, which were assembled into 186,658 contigs. After that, 89,891 representative contigs (without isoform) were clustered. The analysis of the gene expression profiling identified 358 differentially expression genes (DEGs) in the bacterial-resistant group, and 102 DEGs in the bacterial-susceptible group, compared with that in control group. According to the reported references and annotation information from BLAST, GO and KEGG, 30 putative bacterial-resistant genes and 19 putative bacterial-susceptible genes were identified from DEGs. The qRT-PCR results were consistent with the RNA-Seq results. Furthermore, many DGEs were involved in immune signaling related pathways, such as Endocytosis, Lysosome, MAPK, Chemokine and the ERBB signaling pathway.

  2. Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Coelomocytes of Sea Cucumber (Apostichopus japonicus) after Vibrio splendidus Challenge

    PubMed Central

    Gao, Qiong; Liao, Meijie; Wang, Yingeng; Li, Bin; Zhang, Zheng; Rong, Xiaojun; Chen, Guiping; Wang, Lan

    2015-01-01

    Vibrio splendidus is identified as one of the major pathogenic factors for the skin ulceration syndrome in sea cucumber (Apostichopus japonicus), which has vastly limited the development of the sea cucumber culture industry. In order to screen the immune genes involving Vibrio splendidus challenge in sea cucumber and explore the molecular mechanism of this process, the related transcriptome and gene expression profiling of resistant and susceptible biotypes of sea cucumber with Vibrio splendidus challenge were collected for analysis. A total of 319,455,942 trimmed reads were obtained, which were assembled into 186,658 contigs. After that, 89,891 representative contigs (without isoform) were clustered. The analysis of the gene expression profiling identified 358 differentially expression genes (DEGs) in the bacterial-resistant group, and 102 DEGs in the bacterial-susceptible group, compared with that in control group. According to the reported references and annotation information from BLAST, GO and KEGG, 30 putative bacterial-resistant genes and 19 putative bacterial-susceptible genes were identified from DEGs. The qRT-PCR results were consistent with the RNA-Seq results. Furthermore, many DGEs were involved in immune signaling related pathways, such as Endocytosis, Lysosome, MAPK, Chemokine and the ERBB signaling pathway. PMID:26193268

  3. Space Discovery.

    ERIC Educational Resources Information Center

    Blackman, Joan

    1998-01-01

    Describes one teacher's experience taking Space Discovery courses that were sponsored by the United States Space Foundation (USSF). These courses examine the history of space science, theory of orbits and rocketry, the effects of living in outer space on humans, and space weather. (DDR)

  4. Discovery LOX

    NASA Image and Video Library

    2003-11-11

    In the Orbiter Processing Facility, workers prepare to install the liquid oxygen feedline for the 17-inch disconnect on orbiter Discovery. The 17-inch liquid oxygen and liquid hydrogen disconnects provide the propellant feed interface from the external tank to the orbiter main propulsion system and the three Shuttle main engines.

  5. Interoperability and information discovery

    USGS Publications Warehouse

    Christian, E.

    2001-01-01

    In the context of information systems, there is interoperability when the distinctions between separate information systems are not a barrier to accomplishing a task that spans those systems. Interoperability so defined implies that there are commonalities among the systems involved and that one can exploit such commonalities to achieve interoperability. The challenge of a particular interoperability task is to identify relevant commonalities among the systems involved and to devise mechanisms that exploit those commonalities. The present paper focuses on the particular interoperability task of information discovery. The Global Information Locator Service (GILS) is described as a policy, standards, and technology framework for addressing interoperable information discovery on a global and long-term basis. While there are many mechanisms for people to discover and use all manner of data and information resources, GILS initiatives exploit certain key commonalities that seem to be sufficient to realize useful information discovery interoperability at a global, long-term scale. This paper describes ten of the specific commonalities that are key to GILS initiatives. It presents some of the practical implications for organizations in various roles: content provider, system engineer, intermediary, and searcher. The paper also provides examples of interoperable information discovery as deployed using GILS in four types of information communities: bibliographic, geographic, environmental, and government.

  6. 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

  7. 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.

  8. Metabolomics in cancer biomarker discovery: current trends and future perspectives.

    PubMed

    Armitage, Emily G; Barbas, Coral

    2014-01-01

    Cancer is one of the most devastating human diseases that causes a vast number of mortalities worldwide each year. Cancer research is one of the largest fields in the life sciences and despite many astounding breakthroughs and contributions over the past few decades, there is still a considerable amount to unveil on the function of cancer. It is well known that cancer metabolism differs from that of normal tissue and an important hypothesis published in the 1950s by Otto Warburg proposed that cancer cells rely on anaerobic metabolism as the source for energy, even under physiological oxygen levels. Following this, cancer central carbon metabolism has been researched extensively and beyond respiration, cancer has been found to involve a wide range of metabolic processes, and many more are still to be unveiled. Studying cancer through metabolomics could reveal new biomarkers for cancer that could be useful for its future prognosis, diagnosis and therapy. Metabolomics is becoming an increasingly popular tool in the life sciences since it is a relatively fast and accurate technique that can be applied with either a particular focus or in a global manner to reveal new knowledge about biological systems. There have been many examples of its application to reveal potential biomarkers in different cancers that have employed a range of different analytical platforms. In this review, approaches in metabolomics that have been employed in cancer biomarker discovery are discussed and some of the most noteworthy research in the field is highlighted. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Towards our understanding of SARS-CoV, an emerging and devastating but quickly conquered virus.

    PubMed

    Feng, Youjun; Gao, George F

    2007-09-01

    Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus (SARS-CoV), which has overwhelmed more than 30 countries claiming nearly 8400 cases with over 800 fatalities. Thanks to the unprecedented international collaboration, the whole-genomes of SARS-CoVs were successfully deciphered shortly after the identification of the causative pathogen for outbreak of SARS in southern China, in 2003. Hitherto, the SARS-CoV, as a viral paradigm of emerging infectious entities, has been extensively studied that has ranged from epidemiology, molecular virology/immunology to structural genomics. Also, several lines of breakthroughs have been record-brokenly obtained, that included the finding of ACE2, a functional receptor for the SARS-CoV, solution of the 3CL(pro) structure, a first crystal structure of SARS-related macromolecules, revealing of bats as natural reservoirs for SARS-like viruses and the possible involvement of civet cats in the SARS emergence. This review intends to outline the major progress in the journey of SARS-related exploration, by emphasizing those inaugurated studies with milestone-like significance contributed by Chinese research groups.

  10. The politics of lead toxicology and the devastating consequences for children.

    PubMed

    Rosner, David; Markowitz, Gerald

    2007-10-01

    At virtually every step in the history of the uncovering of lead's toxic qualities, resistance was shown by a variety of industrial interests to the association of lead and toxicity. During the first half of the last century, three primary means were used to undermine the growing body of evidence: first, the lead industry sought to control lead research by sponsoring and funding university research. In the 1920s, the General Motors Company, with the aide of DuPont and Standard Oil Companies, established the Kettering Labs, a research unit at the University of Cincinnati which, for many decades was largely supported by industry funds. In the same decade, the lead industry sponsored the research of Joseph Aub at Harvard who worked on neurophysiology of lead. A second way was to shape our understanding of lead itself, portraying it as an indispensable and healthful element essential for all modern life. Lead was portrayed as safe for children to use, be around, and even touch. The third way that lead was exempted from the normal public health measures and regulatory apparatus that had largely controlled phosphorus poisoning, poor quality food and meats and other potential public health hazards was more insidious and involved directly influencing the scientific integrity of the clinical observations and research. Throughout the past century tremendous pressure by the lead industry itself was brought to bear to quiet, even intimidate, researchers and clinicians who reported on or identified lead as a hazard. This article will draw on our previous work and add new documentation of the trajectory of industry attempts to keep out of the public view the tremendous threat of lead poisoning to children. (c) 2007 Wiley-Liss, Inc.

  11. Chronicles in drug discovery.

    PubMed

    Khurdayan, V; Bozzo, J; Sorbera, L

    2005-06-01

    Chronicles in Drug Discovery is a series of brief reports on timely topics in the field of drug R&D. This month's chronicles contain the following reports: Targeting DNA repair enzymes instead of viral proteins provides a great advantage in preventing the emergence of resistant mutants. A striking increase in therapeutic approaches for the treatment of IBD has been fueled by an improved understanding of the mechanisms that underlie its pathophysiology. Peptide deformylase inhibitors are under active investigation for bacterial infections and cancer treatment. Dopamine D3 receptors present an attractive target for alcoholism therapy since they are involved in the mechanisms of alcohol dependency and abuse.

  12. Discovery as a process

    SciTech Connect

    Loehle, C.

    1994-05-01

    The three great myths, which form a sort of triumvirate of misunderstanding, are the Eureka! myth, the hypothesis myth, and the measurement myth. These myths are prevalent among scientists as well as among observers of science. The Eureka! myth asserts that discovery occurs as a flash of insight, and as such is not subject to investigation. This leads to the perception that discovery or deriving a hypothesis is a moment or event rather than a process. Events are singular and not subject to description. The hypothesis myth asserts that proper science is motivated by testing hypotheses, and that if something is not experimentally testable then it is not scientific. This myth leads to absurd posturing by some workers conducting empirical descriptive studies, who dress up their study with a ``hypothesis`` to obtain funding or get it published. Methods papers are often rejected because they do not address a specific scientific problem. The fact is that many of the great breakthroughs in silence involve methods and not hypotheses or arise from largely descriptive studies. Those captured by this myth also try to block funding for those developing methods. The third myth is the measurement myth, which holds that determining what to measure is straightforward, so one doesn`t need a lot of introspection to do science. As one ecologist put it to me ``Don`t give me any of that philosophy junk, just let me out in the field. I know what to measure.`` These myths lead to difficulties for scientists who must face peer review to obtain funding and to get published. These myths also inhibit the study of science as a process. Finally, these myths inhibit creativity and suppress innovation. In this paper I first explore these myths in more detail and then propose a new model of discovery that opens the supposedly miraculous process of discovery to doser scrutiny.

  13. False discoveries and models for gene discovery.

    PubMed

    van den Oord, Edwin J C G; Sullivan, Patrick F

    2003-10-01

    In the search for genes underlying complex traits, there is a tendency to impose increasingly stringent criteria to avoid false discoveries. These stringent criteria make it hard to find true effects, and we argue that it might be better to optimize our procedures for eliminating and controlling false discoveries. Focusing on achieving an acceptable ratio of true- and false-positives, we show that false discoveries could be eliminated much more efficiently using a stepwise approach. To avoid a relatively high false discovery rate, corrections for 'multiple testing' might also be needed in candidate gene studies. If the appropriate methods are used, detecting the proportion of true effects appears to be a more important determinant of the genotyping burden than the desired false discovery rate. This raises the question of whether current models for gene discovery are shaped excessively by a fear of false discoveries.

  14. End-of-life practices in patients with devastating brain injury in Spain: implications for organ donation.

    PubMed

    Domínguez-Gil, B; Coll, E; Pont, T; Lebrón, M; Miñambres, E; Coronil, A; Quindós, B; Herrero, J E; Liébanas, C; Marcelo, B; Sanmartín, A M; Matesanz, R

    2017-04-01

    To describe end-of-life care practices relevant to organ donation in patients with devastating brain injury in Spain. A multicenter prospective study of a retrospective cohort. 1 November 2014 to 30 April 2015. Sixty-eight hospitals authorized for organ procurement. Patients dying from devastating brain injury (possible donors). Age: 1 month-85 years. Type of care, donation after brain death, donation after circulatory death, intubation/ventilation, referral to the donor coordinator. A total of 1,970 possible donors were identified, of which half received active treatment in an Intensive Care Unit (ICU) until brain death (27%), cardiac arrest (5%) or the withdrawal of life-sustaining therapy (19%). Of the rest, 10% were admitted to the ICU to facilitate organ donation, while 39% were not admitted to the ICU. Of those patients who evolved to a brain death condition (n=695), most transitioned to actual donation (n=446; 64%). Of those who died following the withdrawal of life-sustaining therapy (n=537), 45 (8%) were converted into actual donation after circulatory death donors. The lack of a dedicated donation after circulatory death program was the main reason for non-donation. Thirty-seven percent of the possible donors were not intubated/ventilated at death, mainly because the professional in charge did not consider donation alter discarding therapeutic intubation. Thirty-six percent of the possible donors were never referred to the donor coordinator. Although deceased donation is optimized in Spain, there are still opportunities for improvement in the identification of possible donors outside the ICU and in the consideration of donation after circulatory death in patients who die following the withdrawal of life-sustaining therapy. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  15. Devastated but Not Defeated

    ERIC Educational Resources Information Center

    Dyer, Scott

    2005-01-01

    Colleges and universities in other parts of Louisiana and the nation are opening their doors to the 72,000 college students in the greater New Orleans area who were displaced by Hurricane Katrina. Dr. E. Joseph Savoie, Louisiana's commissioner of higher education, says the state's board of regents is making arrangements to allow the students to…

  16. Volcanoes generate devastating waves

    SciTech Connect

    Lockridge, P. )

    1988-01-01

    Although volcanic eruptions can cause many frightening phenomena, it is often the power of the sea that causes many volcano-related deaths. This destruction comes from tsunamis (huge volcano-generated waves). Roughly one-fourth of the deaths occurring during volcanic eruptions have been the result of tsunamis. Moreover, a tsunami can transmit the volcano's energy to areas well outside the reach of the eruption itself. Some historic records are reviewed. Refined historical data are increasingly useful in predicting future events. The U.S. National Geophysical Data Center/World Data Center A for Solid Earth Geophysics has developed data bases to further tsunami research. These sets of data include marigrams (tide gage records), a wave-damage slide set, digital source data, descriptive material, and a tsunami wall map. A digital file contains information on methods of tsunami generation, location, and magnitude of generating earthquakes, tsunami size, event validity, and references. The data can be used to describe areas mot likely to generate tsunamis and the locations along shores that experience amplified effects from tsunamis.

  17. Devastated Stellar Neighborhood

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This image from NASA's Spitzer Space Telescope shows the nasty effects of living near a group of massive stars: radiation and winds from the massive stars (white spot in center) are blasting planet-making material away from stars like our sun. The planetary material can be seen as comet-like tails behind three stars near the center of the picture. The tails are pointing away from the massive stellar furnaces that are blowing them outward.

    The picture is the best example yet of multiple sun-like stars being stripped of their planet-making dust by massive stars.

    The sun-like stars are about two to three million years old, an age when planets are thought to be growing out of surrounding disks of dust and gas. Astronomers say the dust being blown from the stars is from their outer disks. This means that any Earth-like planets forming around the sun-like stars would be safe, while outer planets like Uranus might be nothing more than dust in the wind.

    This image shows a portion of the W5 star-forming region, located 6,500 light-years away in the constellation Cassiopeia. It is a composite of infrared data from Spitzer's infrared array camera and multiband imaging photometer. Light with a wavelength of 3.5 microns is blue, while light from the dust of 24 microns is orange-red.

  18. Devastated but Not Defeated

    ERIC Educational Resources Information Center

    Dyer, Scott

    2005-01-01

    Colleges and universities in other parts of Louisiana and the nation are opening their doors to the 72,000 college students in the greater New Orleans area who were displaced by Hurricane Katrina. Dr. E. Joseph Savoie, Louisiana's commissioner of higher education, says the state's board of regents is making arrangements to allow the students to…

  19. Modern drug discovery technologies: opportunities and challenges in lead discovery.

    PubMed

    Guido, Rafael V C; Oliva, Glaucius; Andricopulo, Adriano D

    2011-12-01

    The identification of promising hits and the generation of high quality leads are crucial steps in the early stages of drug discovery projects. The definition and assessment of both chemical and biological space have revitalized the screening process model and emphasized the importance of exploring the intrinsic complementary nature of classical and modern methods in drug research. In this context, the widespread use of combinatorial chemistry and sophisticated screening methods for the discovery of lead compounds has created a large demand for small organic molecules that act on specific drug targets. Modern drug discovery involves the employment of a wide variety of technologies and expertise in multidisciplinary research teams. The synergistic effects between experimental and computational approaches on the selection and optimization of bioactive compounds emphasize the importance of the integration of advanced technologies in drug discovery programs. These technologies (VS, HTS, SBDD, LBDD, QSAR, and so on) are complementary in the sense that they have mutual goals, thereby the combination of both empirical and in silico efforts is feasible at many different levels of lead optimization and new chemical entity (NCE) discovery. This paper provides a brief perspective on the evolution and use of key drug design technologies, highlighting opportunities and challenges.

  20. Elements of discovery.

    PubMed

    Toledo-Pereyra, Luis H

    2008-01-01

    I understand discovery as the essence of thinking man, or to paraphrase the notable French philosopher René Descartes, "I think, therefore I discover." In this study, I introduce discovery as the foundation of modern science. Discovery consists of six stages or elements, including: concept, belief, ability, support, proof, and protection. Each element is discussed within the context of the whole discovery enterprise. Fundamental tenets for understanding discovery are given throughout the paper, and a few examples illustrate the significance of some of the most important elements. I invite clinicians, researchers, and/or clinical researchers to integrate themselves into the active process of discovery. Remember--I think, therefore I discover.

  1. Landlords and tenants in the wake of abolition and ecological devastation in Brazil's Middle Paraíba Valley.

    PubMed

    Crocitti, John C

    2009-01-01

    This article uses Barra do Piraí as a case study of rural land tenure, production, consumption, and labor in Brazil's Middle Paraíba Valley during the half century following abolition of slavery in 1888. Dairy farming and railroad development distinguished Barra do Piraí from other coffee-producing areas that suffered from ecological devastation. By 1900 the land's loss of fertility precluded further plantation agriculture in Barra do Piraí, leading to the transition from lucrative coffee cultivation to dairy farming based on meager capital inputs. Compared to the earlier coffee culture, dairy farms produced only modest wealth for landlords and required fewer laborers, compelling impoverished tenants to migrate in search of employment. Since Barra do Piraí was an important railroad junction, many rural laborers ended up in the locale after using the railroad as a migratory path. At the same time, the railroad and proto-industries that it stimulated provided alternative employment for rural laborers, thereby partially mitigating the leverage landlords had over the abundant labor force. The availability of industrial and proto-industrial employment created occupational diversity among rural tenants and introduced them to work routines that would become commonplace when the region more fully industrialized after 1940.

  2. Nomogram for Predicting Time to Death After Withdrawal of Life-Sustaining Treatment in Patients With Devastating Neurological Injury.

    PubMed

    He, X; Xu, G; Liang, W; Liu, B; Xu, Y; Luan, Z; Lu, Y; Ko, D S C; Manyalich, M; Schroder, P M; Guo, Z

    2015-08-01

    Reliable prediction of time of death after withdrawal of life-sustaining treatment in patients with devastating neurological injury is crucial to successful donation after cardiac death. Herein, we conducted a study of 419 neurocritical patients who underwent life support withdrawal at four neurosurgical centers in China. Based on a retrospective cohort, we used multivariate Cox regression analysis to identify prognostic factors for patient death, which were then integrated into a nomogram. The model was calibrated and validated using data from an external retrospective cohort and a prospective cohort. We identified 10 variables that were incorporated into a nomogram. The C-indexes for predicting the 60-min death probability in the training, external validation and prospective validation cohorts were 0.96 (0.93-0.98), 0.94 (0.91-0.97), and 0.99 (0.97-1.00), respectively. The calibration plots after WLST showed an optimal agreement between the prediction of time to death by the nomogram and the actual observation for all cohorts. Then we identified 22, 26 and 37 as cut-points for risk stratification into four groups. Kaplan-Meier curves indicated distinct prognoses between patients in the different risk groups (p < 0.001). In conclusion, we have developed and validated a nomogram to accurately identify potential cardiac death donors in neurocritical patients in a Chinese population. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Commentary: The devastating effects of ignoring child maltreatment in psychiatry--a commentary on Teicher and Samson 2016.

    PubMed

    van der Kolk, Bessel

    2016-03-01

    Despite the numerous studies over the past 30 years that have clarified the devastating effects of child maltreatment on mental and physical health, the role of trauma within the caregiving system remains unrecognized both in our diagnostic systems and in our dominant treatment paradigms. Research of people with histories of caregiver abuse and neglect consistently demonstrates problems with concentration, anger, panic, depression, food intake, drugs, and sleep, as well as decreased Heart RateVariability, higher levels of stress hormones, and reduced or impaired immune response. Their relationship between documented brain changes and psychopathology is complex. Traumatic life experiences during childhood and adolescence are far more common than expected. The Centers for Disease Control and Prevention estimates that child maltreatment may be the most costly public health issue in the United States, Eradicating child abuse in America would reduce the overall rate of depression by more than half, alcoholism by two-thirds, and suicide, serious drug abuse, and domestic violence by three quarters. It would also have a significantly positive effect on workplace performance, and vastly decrease the need for incarceration. The current practice of applying multiple distinct comorbid diagnoses to traumatized children prevents a comprehensive treatment approach. Approaching their problems from a framework of memories of discreet traumatic ignores the fact that the damage affects the brain's neural circuitry and goes well beyond dealing with discrete painful events. Our great challenge is to learn to utilize the brain's neuroplasticity to reorganize defective brain circuits.

  4. A Discovery-Based Experiment Involving Rearrangement in the Conversion of Alcohols to Alkyl Halides: Permanent Magnet [to the thirteenth power]C NMR in the First-Semester Organic Chemistry Lab

    ERIC Educational Resources Information Center

    Kjonaas, Richard A.; Tucker, Ryand J. F.

    2008-01-01

    The use of permanent magnet [to the thirteenth power]C NMR in large-section first-semester organic chemistry lab courses is limited by the availability of experiments that not only hinge on first-semester lecture topics, but which also produce at least 0.5 mL of neat liquid sample. This article reports a discovery-based experiment that meets both…

  5. VARIABLES IN "DISCOVERY LEARNING."

    ERIC Educational Resources Information Center

    GLASER, ROBERT

    A PRESENTATION WAS MADE OF THE ANALYSIS OF BEHAVIOR THAT IS REQUIRED AS A FIRST STEP IN THE PROCESS OF DEVELOPING PROCEDURES AND MATERIALS FOR "DISCOVERY LEARNING." TEACHING BY THE DISCOVERY METHOD IS DESCRIBED AS REQUIRING THAT A MINIMUM OF STRUCTURED INSTRUCTIONAL SEQUENCE BE IMPOSED TO ALLOW THE CHILD TO (1) LEARN BY DISCOVERY AND (2)…

  6. Mitochondrial DNA Reveals the Trace of the Ancient Settlers of a Violently Devastated Late Bronze and Iron Ages Village

    PubMed Central

    Núñez, Carolina; Baeta, Miriam; Cardoso, Sergio; Palencia-Madrid, Leire; García-Romero, Noemí; Llanos, Armando; M. de Pancorbo, Marian

    2016-01-01

    La Hoya (Alava, Basque Country) was one of the most important villages of the Late Bronze and Iron Ages of the north of the Iberian Peninsula, until it was violently devastated around the 4th century and abandoned in the 3rd century B.C. Archaeological evidences suggest that descendants from La Hoya placed their new settlement in a nearby hill, which gave rise to the current village of Laguardia. In this study, we have traced the genetic imprints of the extinct inhabitants of La Hoya through the analysis of maternal lineages. In particular, we have analyzed the mitochondrial DNA (mtDNA) control region of 41 human remains recovered from the archaeological site for comparison with a sample of 51 individuals from the geographically close present-day population of Laguardia, as well as 56 individuals of the general population of the province of Alava, where the archaeological site and Laguardia village are located. MtDNA haplotypes were successfully obtained in 25 out of 41 ancient samples, and 14 different haplotypes were identified. The major mtDNA subhaplogroups observed in La Hoya were H1, H3, J1 and U5, which show a distinctive frequency pattern in the autochthonous populations of the north of the Iberian Peninsula. Approximate Bayesian Computation analysis was performed to test the most likely model for the local demographic history. The results did not sustain a genealogical continuity between Laguardia and La Hoya at the haplotype level, although factors such as sampling effects, recent admixture events, and genetic bottlenecks need to be considered. Likewise, the highly similar subhaplogroup composition detected between La Hoya and Laguardia and Alava populations do not allow us to reject a maternal genetic continuity in the human groups of the area since at least the Iron Age to present times. Broader analyses, based on a larger collection of samples and genetic markers, would be required to study fine-scale population events in these human groups. PMID

  7. Mitochondrial DNA Reveals the Trace of the Ancient Settlers of a Violently Devastated Late Bronze and Iron Ages Village.

    PubMed

    Núñez, Carolina; Baeta, Miriam; Cardoso, Sergio; Palencia-Madrid, Leire; García-Romero, Noemí; Llanos, Armando; M de Pancorbo, Marian

    2016-01-01

    La Hoya (Alava, Basque Country) was one of the most important villages of the Late Bronze and Iron Ages of the north of the Iberian Peninsula, until it was violently devastated around the 4th century and abandoned in the 3rd century B.C. Archaeological evidences suggest that descendants from La Hoya placed their new settlement in a nearby hill, which gave rise to the current village of Laguardia. In this study, we have traced the genetic imprints of the extinct inhabitants of La Hoya through the analysis of maternal lineages. In particular, we have analyzed the mitochondrial DNA (mtDNA) control region of 41 human remains recovered from the archaeological site for comparison with a sample of 51 individuals from the geographically close present-day population of Laguardia, as well as 56 individuals of the general population of the province of Alava, where the archaeological site and Laguardia village are located. MtDNA haplotypes were successfully obtained in 25 out of 41 ancient samples, and 14 different haplotypes were identified. The major mtDNA subhaplogroups observed in La Hoya were H1, H3, J1 and U5, which show a distinctive frequency pattern in the autochthonous populations of the north of the Iberian Peninsula. Approximate Bayesian Computation analysis was performed to test the most likely model for the local demographic history. The results did not sustain a genealogical continuity between Laguardia and La Hoya at the haplotype level, although factors such as sampling effects, recent admixture events, and genetic bottlenecks need to be considered. Likewise, the highly similar subhaplogroup composition detected between La Hoya and Laguardia and Alava populations do not allow us to reject a maternal genetic continuity in the human groups of the area since at least the Iron Age to present times. Broader analyses, based on a larger collection of samples and genetic markers, would be required to study fine-scale population events in these human groups.

  8. Acute stress-related psychological impact in children following devastating natural disaster, the Sikkim earthquake (2011), India

    PubMed Central

    Mondal, Rakesh; Sarkar, Sumantra; Banerjee, Indira; Hazra, Avijit; Majumder, Debabrata; Sabui, Tapas; Dutta, Sudip; Saren, Abhisek; Pan, Partha

    2013-01-01

    Background: Psychological stress following natural disaster is common. Despite several earthquakes in India, data on evaluation of acute stress among the child victims in the early postdisaster period is scarce. Immediately following a devastating earthquake (6.9 Richter) at Sikkim on September, 18 2011, many children attended North Bengal Medical College, the nearest government tertiary care institution, with unusual stress symptoms. Objective: Evaluation of acute stress symptoms in children in the immediate postearthquake period. Materials and Methods: This was a cross-sectional study done over 4 weeks and includes all the children from 1 to 12 years presenting with unusual physical or behavioral symptoms. Those with major injuries requiring admission were excluded. They were divided into two age groups. For older children (8-12 years) the 8-item Children Impact of Event Scale (CIES) was used for screening of stress. Unusual symptoms were recorded in younger children (1-8 years) as CIES is not validated < 8 years. Result: A total of 84 children (2.66%) out of 3154 had stress symptoms. Maximum attendance was noted in first 3 days (65.47%) and declined gradually. In children ≥ 8 years, 48.78% had psychological stress, which was statistically significant on CIES scores without any gender predilection. Static posturing (41.86%), sleeplessness (32.55%), anorexia (9.30%), recurrent vomiting (13.95%), excessive crying (13.95%), or night-awakenings (4.65%) were found in younger children (n = 43) and three required admission. Conclusion: This study represent the first Indian data showing statistically significant psychological impact in older children (8-12 years) and various forms of physical stress symptoms in young children (1-8 years) following earthquake. PMID:24174793

  9. Design for a Superconductor Discovery Engine (SCODEngine)

    NASA Astrophysics Data System (ADS)

    Isikaku-Ironkwe, O. Paul

    2010-03-01

    One of the grand challenges of superconductivity is achieving a paradigm shift from discovery by serendipity to discovery by design. Periodic Table-based Maps that involve electronegativity, valence electrons and atomic number that correlate with superconducting transition temperature can be used to design novel superconductors. Combining these maps with experimental databases on superconductors, databases of crystal structures and integrating material design software engine, we can re-design many known superconductor families and predict novel systems. By adding search engine technology with a ``knowledge discovery engine'', we produce a superconductor discovery engine (SCODEngine). The SCODEngine enables us to discover novel superconductors with the accelerated speed of a Google search. We have produced a primitive SCODEngine that may revolutionize novel superconductor search and discovery.

  10. [My accidental discovery].

    PubMed

    Nakamura, Tatsuya

    2008-10-01

    We wonder what we should do in medical care besides daily routine work as a laboratory technician. I made a discovery in my routine laboratory work, which gave me a theme for my research. This led to me successfully completing a number of scientific research projects, and these experiences have enabled me to be able to give advice on appropriate treatments for infectious diseases in medical care. It was March 1999 when I identified Escherichia coli (E. coli) in an intra-abdominal abscess resistant to antibacterial agents. The E. coli was producing an enzyme, extended-spectrum-beta-lactamase (ESBL), that breaks down cefem-group antibiotics often used in Japan. Therefore, it was resistant to those antimicrobial agents. Detailed analysis was performed by us and researchers of the National Institute of Infectious Diseases, which revealed that the E. coli had a SHV12 genotype of ESBL. It was the first case report of this type of ESBL-producing E. coli infection in Japan. After this experience, I became interested in searching for the mechanism of resistance to antibiotics with various kinds of approaches, such as a method involving genomic analysis by the polymerase-chain reaction (PCR), therapeutic management of drug-resistant bacterial infection, and so on, through which I learned a series of investigative approaches. Since I had plenty of data and experiences generated from routine work, I could perform novel studies and obtained many interesting findings. I am feeding back these findings to routine work in order to improve my performance. From my experience, we should look for the seeds for research from routine work as much as possible, and knowledge and experience generated by resolving problems teaches us how to perform in a clinical setting. This may lead to the further development of our research, which, in turn, promotes the accumulation of knowledge and experience. This feed-forward cycle enables laboratory technicians to improve their quality of work. This I

  11. NASA Discovery Program Workshop

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The purpose of the workshop was to review concepts for Discover-class missions that would follow the first two missions (MESUR-Pathfinder and NEAR) of this new program. The concepts had been generated by scientists involved in NASA's Solar System Exploration Program to carry out scientifically important investigations within strict guidelines -- $150 million cap on development cost and 3 year cap on development schedule. Like the Astrophysics Small Explorers (SMEX), such 'faster and cheaper' missions could provide vitality to solar system exploration research by returning high quality data more frequently and regularly and by involving many more young researchers than normally participate directly in larger missions. An announcement of opportunity (AO) to propose a Discovery mission to NASA is expected to be released in about two years time. One purpose of the workshop was to assist Code SL in deciding how to allocate its advanced programs resources. A second, complimentary purpose was to provide the concept proposers with feedback to allow them to better prepare for the AO.

  12. The discovery of the structure of DNA

    NASA Astrophysics Data System (ADS)

    Squires, G. L.

    2003-04-01

    On 25 April 1953, Nature published a letter by Francis Crick and James Watson, at the Cavendish Laboratory, Cambridge, proposing a structure for DNA. This letter marked the beginning of a revolution in biology. Besides Crick and Watson, two other scientists, Rosalind Franklin and Maurice Wilkins, played key roles in the discovery. After sketching the early careers of the four scientists, the present article gives an account of the physics and chemistry involved in the discovery, and the events leading up to it.

  13. STS-92 Discovery Launch

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Viewed from across the waters of Banana Creek, clouds of smoke and steam are illuminated by the flames from Space Shuttle Discovery'''s perfect on-time launch at 7:17 p.m. EDT. Discovery carries a crew of seven on a construction flight to the International Space Station. Discovery also carries a payload that includes the Integrated Truss Structure Z-1, first of 10 trusses that will form the backbone of the Space Station, and the third Pressurized Mating Adapter that will provide a Shuttle docking port for solar array installation on the sixth Station flight and Lab installation on the seventh Station flight. Discovery'''s landing is expected Oct. 22 at 2:10 p.m. EDT.

  14. Computational drug discovery

    PubMed Central

    Ou-Yang, Si-sheng; Lu, Jun-yan; Kong, Xiang-qian; Liang, Zhong-jie; Luo, Cheng; Jiang, Hualiang

    2012-01-01

    Computational drug discovery is an effective strategy for accelerating and economizing drug discovery and development process. Because of the dramatic increase in the availability of biological macromolecule and small molecule information, the applicability of computational drug discovery has been extended and broadly applied to nearly every stage in the drug discovery and development workflow, including target identification and validation, lead discovery and optimization and preclinical tests. Over the past decades, computational drug discovery methods such as molecular docking, pharmacophore modeling and mapping, de novo design, molecular similarity calculation and sequence-based virtual screening have been greatly improved. In this review, we present an overview of these important computational methods, platforms and successful applications in this field. PMID:22922346

  15. Discovery and Classification in Astronomy

    NASA Astrophysics Data System (ADS)

    Dick, Steven J.

    2013-10-01

    Preface; Abbreviations; Introduction: the natural history of the heavens and the natural history of discovery; Part I. Entrée: 1. The Pluto affair; Part II. Narratives of Discovery: 2. Moons, rings, and asteroids: discovery in the realm of the planets; 3. In Herschel's gardens: nebulous discoveries in the realm of the stars; 4. Dwarfs, giants, and planets (again!): the discovery of the stars themselves; 5. Galaxies, quasars, and clusters: discovery in the realm of the galaxies; Part III. Patterns of Discovery: 6. The structure of discovery; 7. The varieties of discovery; 8. Discovery and classification; Part IV. Drivers of Discovery: 9. Technology and theory as drivers of discovery; Part V. The Synthesis of Discovery: 10. Luxuriant gardens and the master narrative; 11. The meaning of discovery; Appendix I; Appendix II.

  16. Decades of Discovery

    DOE R&D Accomplishments Database

    2011-06-01

    For the past two-and-a-half decades, the Office of Science at the U.S. Department of Energy has been at the forefront of scientific discovery. Over 100 important discoveries supported by the Office of Science are represented in this document.

  17. The n = 0 Discovery

    NASA Astrophysics Data System (ADS)

    Witten, Thomas A.

    We describe Pierre-Gilles de Gennes' 1972 letter explaining polymer swelling as a form of critical phenomenon. We trace the impact of this "n = 0" discovery on polymer theory and experiment. We discuss later developments in mainstream statistical physics that reflect the n = 0 insight of this paper. We collect the views of several leading statistical physicists on the significance of the discovery.

  18. Serendipity and Scientific Discovery.

    ERIC Educational Resources Information Center

    Rosenman, Martin F.

    1988-01-01

    The discovery of penicillin is cited in a discussion of the role of serendipity as it relates to scientific discovery. The importance of sagacity as a personality trait is noted. Successful researchers have questioning minds, are willing to view data from several perspectives, and recognize and appreciate the unexpected. (JW)

  19. Serendipity and Scientific Discovery.

    ERIC Educational Resources Information Center

    Rosenman, Martin F.

    1988-01-01

    The discovery of penicillin is cited in a discussion of the role of serendipity as it relates to scientific discovery. The importance of sagacity as a personality trait is noted. Successful researchers have questioning minds, are willing to view data from several perspectives, and recognize and appreciate the unexpected. (JW)

  20. Friends' Discovery Camp

    ERIC Educational Resources Information Center

    Seymour, Seth

    2008-01-01

    This article features Friends' Discovery Camp, a program that allows children with and without autism spectrum disorder to learn and play together. In Friends' Discovery Camp, campers take part in sensory-rich experiences, ranging from hands-on activities and performing arts to science experiments and stories teaching social skills. Now in its 7th…

  1. "Eureka, Eureka!" Discoveries in Science

    ERIC Educational Resources Information Center

    Agarwal, Pankaj

    2011-01-01

    Accidental discoveries have been of significant value in the progress of science. Although accidental discoveries are more common in pharmacology and chemistry, other branches of science have also benefited from such discoveries. While most discoveries are the result of persistent research, famous accidental discoveries provide a fascinating…

  2. "Eureka, Eureka!" Discoveries in Science

    ERIC Educational Resources Information Center

    Agarwal, Pankaj

    2011-01-01

    Accidental discoveries have been of significant value in the progress of science. Although accidental discoveries are more common in pharmacology and chemistry, other branches of science have also benefited from such discoveries. While most discoveries are the result of persistent research, famous accidental discoveries provide a fascinating…

  3. Postgenomic strategies in antibacterial drug discovery.

    PubMed

    Brötz-Oesterhelt, Heike; Sass, Peter

    2010-10-01

    During the last decade the field of antibacterial drug discovery has changed in many aspects including bacterial organisms of primary interest, discovery strategies applied and pharmaceutical companies involved. Target-based high-throughput screening had been disappointingly unsuccessful for antibiotic research. Understanding of this lack of success has increased substantially and the lessons learned refer to characteristics of targets, screening libraries and screening strategies. The 'genomics' approach was replaced by a diverse array of discovery strategies, for example, searching for new natural product leads among previously abandoned compounds or new microbial sources, screening for synthetic inhibitors by targeted approaches including structure-based design and analyses of focused libraries and designing resistance-breaking properties into antibiotics of established classes. Furthermore, alternative treatment options are being pursued including anti-virulence strategies and immunotherapeutic approaches. This article summarizes the lessons learned from the genomics era and describes discovery strategies resulting from that knowledge.

  4. Purposive discovery of operations

    NASA Technical Reports Server (NTRS)

    Sims, Michael H.; Bresina, John L.

    1992-01-01

    The Generate, Prune & Prove (GPP) methodology for discovering definitions of mathematical operators is introduced. GPP is a task within the IL exploration discovery system. We developed GPP for use in the discovery of mathematical operators with a wider class of representations than was possible with the previous methods by Lenat and by Shen. GPP utilizes the purpose for which an operator is created to prune the possible definitions. The relevant search spaces are immense and there exists insufficient information for a complete evaluation of the purpose constraint, so it is necessary to perform a partial evaluation of the purpose (i.e., pruning) constraint. The constraint is first transformed so that it is operational with respect to the partial information, and then it is applied to examples in order to test the generated candidates for an operator's definition. In the GPP process, once a candidate definition survives this empirical prune, it is passed on to a theorem prover for formal verification. We describe the application of this methodology to the (re)discovery of the definition of multiplication for Conway numbers, a discovery which is difficult for human mathematicians. We successfully model this discovery process utilizing information which was reasonably available at the time of Conway's original discovery. As part of this discovery process, we reduce the size of the search space from a computationally intractable size to 3468 elements.

  5. Discovery and structural characterization of a new inhibitor series of HIV-1 nucleocapsid function: NMR solution structure determination of a ternary complex involving a 2:1 inhibitor/NC stoichiometry.

    PubMed

    Goudreau, Nathalie; Hucke, Oliver; Faucher, Anne-Marie; Grand-Maître, Chantal; Lepage, Olivier; Bonneau, Pierre R; Mason, Stephen W; Titolo, Steve

    2013-06-12

    The nucleocapsid (NC) protein is an essential factor with multiple functions within the human immunodeficiency virus type 1 (HIV-1) replication cycle. In this study, we describe the discovery of a novel series of inhibitors that targets HIV-1 NC protein by blocking its interaction with nucleic acids. This series was identified using a previously described capsid (CA) assembly assay, employing a recombinant HIV-1 CA-NC protein and immobilized TG-rich deoxyoligonucleotides. Using visible absorption spectroscopy, we were able to demonstrate that this new inhibitor series binds specifically and reversibly to the NC with a peculiar 2:1 stoichiometry. A fluorescence-polarization-based binding assay was also developed in order to monitor the inhibitory activities of this series of inhibitors. To better characterize the structural aspect of inhibitor binding onto NC, we performed NMR studies using unlabeled and (13)C,(15)N-double-labeled NC(1-55) protein constructs. This allowed the determination of the solution structure of a ternary complex characterized by two inhibitor molecules binding to the two zinc knuckles of the NC protein. To the best of our knowledge, this represents the first report of a high-resolution structure of a small-molecule inhibitor bound to NC, demonstrating sub-micromolar potency and moderate antiviral potency with one analogue of the series. This structure was compared with available NC/oligonucleotide complex structures and further underlined the high flexibility of the NC protein, allowing it to adopt many conformations in order to bind its different oligonucleotide/nucleomimetic targets. In addition, analysis of the interaction details between the inhibitor molecules and NC demonstrated how this novel inhibitor series is mimicking the guanosine nucleobases found in many reported complex structures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Viral surveillance and discovery.

    PubMed

    Lipkin, Walter Ian; Firth, Cadhla

    2013-04-01

    The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Space Shuttle Discovery Landing

    NASA Image and Video Library

    2012-04-17

    Space shuttle Discovery, mounted atop a NASA 747 Shuttle Carrier Aircraft (SCA) lands at Washington Dulles International Airport, Tuesday, April 17, 2012, in Sterling, Va. Discovery, the first orbiter retired from NASA’s shuttle fleet, completed 39 missions, spent 365 days in space, orbited the Earth 5,830 times, and traveled 148,221,675 miles. NASA will transfer Discovery to the National Air and Space Museum to begin its new mission to commemorate past achievements in space and to educate and inspire future generations of explorers. Photo Credit: (NASA/Smithsonian Institution/Eric Long)

  8. Space Shuttle Discovery Landing

    NASA Image and Video Library

    2012-04-17

    Space shuttle Discovery, mounted atop a NASA 747 Shuttle Carrier Aircraft (SCA) taxis in front of the main terminal at Washington Dulles International Airport, Tuesday, April 17, 2012, in Sterling, Va. Discovery, the first orbiter retired from NASA’s shuttle fleet, completed 39 missions, spent 365 days in space, orbited the Earth 5,830 times, and traveled 148,221,675 miles. NASA will transfer Discovery to the National Air and Space Museum to begin its new mission to commemorate past achievements in space and to educate and inspire future generations of explorers. Photo Credit: (NASA/Smithsonian Institution/Eric Long)

  9. Space Shuttle Discovery Landing

    NASA Image and Video Library

    2012-04-17

    Space shuttle Discovery, mounted atop a NASA 747 Shuttle Carrier Aircraft (SCA) lands at Washington Dulles International Airport, Tuesday, April 17, 2012, in Sterling, Va. The Steven F. Udvar-Hazy Center is seen in the background. Discovery, the first orbiter retired from NASA’s shuttle fleet, completed 39 missions, spent 365 days in space, orbited the Earth 5,830 times, and traveled 148,221,675 miles. NASA will transfer Discovery to the National Air and Space Museum to begin its new mission to commemorate past achievements in space and to educate and inspire future generations of explorers. Photo Credit: (NASA/Smithsonian Institution/Eric Long)

  10. Enabling the Discovery of Gravitational Radiation

    NASA Astrophysics Data System (ADS)

    Isaacson, Richard

    2017-01-01

    The discovery of gravitational radiation was announced with the publication of the results of a physics experiment involving over a thousand participants. This was preceded by a century of theoretical work, involving a similarly large group of physicists, mathematicians, and computer scientists. This huge effort was enabled by a substantial commitment of resources, both public and private, to develop the different strands of this complex research enterprise, and to build a community of scientists to carry it out. In the excitement following the discovery, the role of key enablers of this success has not always been adequately recognized in popular accounts. In this talk, I will try to call attention to a few of the key ingredients that proved crucial to enabling the successful discovery of gravitational waves, and the opening of a new field of science.

  11. The Learning Discovery

    ERIC Educational Resources Information Center

    Prout, Joan

    1975-01-01

    The learning discovery of youngsters is a do-it-yourself teaching method for clerical, administrative, and accountant trainees at the Bankside House headquarters of the Central Electricity Generating Board's South Eastern Region, London. (Author)

  12. Toxins and drug discovery.

    PubMed

    Harvey, Alan L

    2014-12-15

    Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  13. The Discovery of Noggin.

    ERIC Educational Resources Information Center

    Oppenheimer, Steven B.

    1995-01-01

    Discusses recently published work that appears to have many of the answers to the question of how the nervous system develops. Focuses on the discovery of what is believed to be neural inducer, a protein called noggin. (LZ)

  14. Discovery Touches Down!

    NASA Image and Video Library

    Discovery has completed its final mission, STS-133, for NASA's Space Shuttle Program landing on-time at Kennedy Space Center in Florida at 11:57 a.m. EST, March 9, 2011 after 202 orbits around Eart...

  15. Platforms for antibiotic discovery.

    PubMed

    Lewis, Kim

    2013-05-01

    The spread of resistant bacteria, leading to untreatable infections, is a major public health threat but the pace of antibiotic discovery to combat these pathogens has slowed down. Most antibiotics were originally isolated by screening soil-derived actinomycetes during the golden era of antibiotic discovery in the 1940s to 1960s. However, diminishing returns from this discovery platform led to its collapse, and efforts to create a new platform based on target-focused screening of large libraries of synthetic compounds failed, in part owing to the lack of penetration of such compounds through the bacterial envelope. This article considers strategies to re-establish viable platforms for antibiotic discovery. These include investigating untapped natural product sources such as uncultured bacteria, establishing rules of compound penetration to enable the development of synthetic antibiotics, developing species-specific antibiotics and identifying prodrugs that have the potential to eradicate dormant persisters, which are often responsible for hard-to-treat infections.

  16. Antibiotic drug discovery.

    PubMed

    Wohlleben, Wolfgang; Mast, Yvonne; Stegmann, Evi; Ziemert, Nadine

    2016-09-01

    Due to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a 'New Age of Antibiotic Discovery'. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  17. The requirements discovery process

    SciTech Connect

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

    1997-02-01

    Cost and schedule overruns are often caused by poor requirements that are produced by people who do not understand the requirement process. This paper provides a high-level overview of the requirements discovery process.

  18. Space Shuttle Discovery Launch

    NASA Image and Video Library

    2011-02-24

    NASA Administrator Charles Bolden and other NASA management watch the launch of space shuttle Discovery (STS-133) from the firing room at Kennedy Space Center, Thursday, Feb. 24, 2011, in Cape Canaveral, Fla. Discovery, on its 39th and final flight, is carrying the Italian-built Permanent Multipurpose Module (PMM), Express Logistics Carrier 4 (ELC4) and Robonaut 2, the first humanoid robot in space to the International Space Station. Photo Credit: (NASA/Bill Ingalls)

  19. Space Shuttle Discovery Launch

    NASA Image and Video Library

    2011-02-24

    NASA management watch the launch of space shuttle Discovery (STS-133) from the firing room at Kennedy Space Center, Thursday, Feb. 24, 2011, in Cape Canaveral, Fla. Discovery, on its 39th and final flight, is carrying the Italian-built Permanent Multipurpose Module (PMM), Express Logistics Carrier 4 (ELC4) and Robonaut 2, the first humanoid robot in space to the International Space Station. Photo Credit: (NASA/Bill Ingalls)

  20. STS-133 Discovery

    NASA Image and Video Library

    2010-11-03

    An faint profile outline of the space shuttle Discovery and launch pad 39a are seen projected in the sky as powerful xenon lights illuminate launch pad 39a on Wednesday, Nov. 3, 2010 at the NASA Kennedy Space Center in Cape Canaveral, Fla. During space shuttle Discovery's final spaceflight, the STS-133 crew members will take important spare parts to the International Space Station along with the Express Logistics Carrier-4. Photo Credit: (NASA/Bill Ingalls)

  1. Comets: Search and Discovery

    NASA Astrophysics Data System (ADS)

    Shanklin, J.; Murdin, P.

    2003-04-01

    Comet discovery in the traditional sense by an amateur astronomer may be a thing of the past. The development of increasing numbers of professional all-sky survey programs, many specifically designed to spot moving or changing objects, means that the future prospects for visual discovery of a comet by an amateur astronomer are bleak. In the near future the professional programs are likely to cover...

  2. Space Shuttle Discovery Launch

    NASA Image and Video Library

    2008-05-31

    NASA Shuttle Launch Director Michael Leinbach, left, STS-124 Assistant Launch Director Ed Mango, center, and Flow Director for Space Shuttle Discovery Stephanie Stilson clap in the the Launch Control Center after the main engine cut off and successful launch of the Space Shuttle Discovery (STS-124) Saturday, May 31, 2008, at the Kennedy Space Center in Cape Canaveral, Fla. The Shuttle lifted off from launch pad 39A at 5:02 p.m. EDT. Photo Credit: (NASA/Bill Ingalls)

  3. Sequences in drug discovery.

    PubMed

    Khurdayan, V; Davies, S

    2005-04-01

    Sequences in Drug Discovery is a new series of distinct brief reports on breaking topics in the field of drug R&D. This month's Sequences in Drug Discovery contains the following reports: Spotlight on West Nile virus vaccines. p38alpha MAPK--a dynamic target in rheumatoid arthritis. The need for new contraceptives: targeting PDE3. Vasopeptidase inhibition with a triple mode of action. Current advances in the development of 5-HT(6) receptor antagonists.

  4. A model for emergency department end-of-life communications after acute devastating events--part I: decision-making capacity, surrogates, and advance directives.

    PubMed

    Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

    2012-09-01

    Making decisions for a patient affected by sudden devastating illness or injury traumatizes a patient's family and loved ones. Even in the absence of an emergency, surrogates making end-of-life treatment decisions may experience negative emotional effects. Helping surrogates with these end-of-life decisions under emergent conditions requires the emergency physician (EP) to be clear, making medical recommendations with sensitivity. This model for emergency department (ED) end-of-life communications after acute devastating events comprises the following steps: 1) determine the patient's decision-making capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed in completed advance directives; 4) determine patient/surrogate understanding of the life-limiting event and expectant treatment goals; 5) convey physician understanding of the event, including prognosis, treatment options, and recommendation; 6) share decisions regarding withdrawing or withholding of resuscitative efforts, using available resources and considering options for organ donation; and 7) revise treatment goals as needed. Emergency physicians should break bad news compassionately, yet sufficiently, so that surrogate and family understand both the gravity of the situation and the lack of long-term benefit of continued life-sustaining interventions. EPs should also help the surrogate and family understand that palliative care addresses comfort needs of the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of this communications model reviews determination of decision-making capacity, surrogacy laws, and advance directives, including legal definitions and application of these steps; Part II (which will appear in a future issue of AEM) covers communication moving from resuscitative to end-of-life and palliative treatment. EPs should recognize acute devastating illness or injuries, when appropriate, as opportunities to initiate end-of-life discussions and to

  5. 47 CFR 1.729 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., and Reports Involving Common Carriers Formal Complaints § 1.729 Discovery. (a) Subject to paragraph (i... other electronic format that provides: (1) Indexing by useful identifying information about the... witnesses shall be subject to deposition in Accelerated Docket proceedings under the same rules...

  6. The Discovery of Insulin: A Case Study of Scientific Methodology

    ERIC Educational Resources Information Center

    Stansfield, William D.

    2012-01-01

    The nature of scientific research sometimes involves a trial-and-error procedure. Popular reviews of successful results from this approach often sanitize the story by omitting unsuccessful trials, thus painting the rosy impression that research simply follows a direct route from hypothesis to experiment to scientific discovery. The discovery of…

  7. The Discovery of Insulin: A Case Study of Scientific Methodology

    ERIC Educational Resources Information Center

    Stansfield, William D.

    2012-01-01

    The nature of scientific research sometimes involves a trial-and-error procedure. Popular reviews of successful results from this approach often sanitize the story by omitting unsuccessful trials, thus painting the rosy impression that research simply follows a direct route from hypothesis to experiment to scientific discovery. The discovery of…

  8. Cyberinfrastructure for Atmospheric Discovery

    NASA Astrophysics Data System (ADS)

    Wilhelmson, R.; Moore, C. W.

    2004-12-01

    Each year across the United States, floods, tornadoes, hail, strong winds, lightning, hurricanes, and winter storms cause hundreds of deaths, routinely disrupt transportation and commerce, and result in billions of dollars in annual economic losses . MEAD and LEAD are two recent efforts aimed at developing the cyberinfrastructure for studying and forecasting these events through collection, integration, and analysis of observational data coupled with numerical simulation, data mining, and visualization. MEAD (Modeling Environment for Atmospheric Discovery) has been funded for two years as an NCSA (National Center for Supercomputing Applications) Alliance Expedition. The goal of this expedition has been the development/adaptation of cyberinfrastructure that will enable research simulations, datamining, machine learning and visualization of hurricanes and storms utilizing the high performance computing environments including the TeraGrid. Portal grid and web infrastructure are being tested that will enable launching of hundreds of individual WRF (Weather Research and Forecasting) simulations. In a similar way, multiple Regional Ocean Modeling System (ROMS) or WRF/ROMS simulations can be carried out. Metadata and the resulting large volumes of data will then be made available for further study and for educational purposes using analysis, mining, and visualization services. Initial coupling of the ROMS and WRF codes has been completed and parallel I/O is being implemented for these models. Management of these activities (services) are being enabled through Grid workflow technologies (e.g. OGCE). LEAD (Linked Environments for Atmospheric Discovery) is a recently funded 5-year, large NSF ITR grant that involves 9 institutions who are developing a comprehensive national cyberinfrastructure in mesoscale meteorology, particularly one that can interoperate with others being developed. LEAD is addressing the fundamental information technology (IT) research challenges needed

  9. A matched case-control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication.

    PubMed

    Conrad, A; Le Maréchal, M; Dupont, D; Ducastelle-Leprêtre, S; Balsat, M; Labussière-Wallet, H; Barraco, F; Nicolini, F-E; Thomas, X; Gilis, L; Chidiac, C; Ferry, T; Wallet, F; Rabodonirina, M; Salles, G; Michallet, M; Ader, F

    2016-07-01

    Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p <0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-α blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients.

  10. Landmark discoveries in intracellular transport and secretion

    PubMed Central

    Paknikar, Kishore M

    2007-01-01

    Abstract Cellular protein transport and secretion is fundamental to the very existence of an organism, regulating important physiological functions such as reproduction, digestion, energy production, growth, neurotransmission, hormone release, water and ion transport, etc., all required for the survival and maintenance of homeostasis within an organism. Molecular understanding of transport and secretion of intracellular product has therefore been of paramount importance and aggressively investigated for over six decades. Only in the last 20 years, the general molecular mechanism of the process has come to light, following discovery of key proteins involved in ER-Golgi transport, and discovery of the ‘porosome’– the universal secretion machinery in cells. PMID:17635635

  11. Space Shuttle Discovery Landing

    NASA Image and Video Library

    2012-04-17

    NASA Deputy Administrator Lori Garver, at podium, speaks to those in attendance at Apron W after the 747 Shuttle Carrier Aircraft (SCA) with space shuttle Discovery mounted on top rolled to a halt at Washington Dulles International Airport, Tuesday, April 17, 2012 in Sterling, Va. Discovery, the first orbiter retired from NASA’s shuttle fleet, completed 39 missions, spent 365 days in space, orbited the Earth 5,830 times, and traveled 148,221,675 miles. NASA will transfer Discovery to the National Air and Space Museum to begin its new mission to commemorate past achievements in space and to educate and inspire future generations of explorers. Photo Credit: (NASA/Smithsonian Institution/Dane Penland)

  12. Discovery Orbiter Major Modifications

    NASA Image and Video Library

    2003-08-27

    During power-up of the orbiter Discovery in the Orbiter Processing Facility, a technician moves a circuit reset on the cockpit console. Discovery has been undergoing Orbiter Major Modifications in the past year, ranging from wiring, control panels and black boxes to gaseous and fluid systems tubing and components. These systems were deserviced, disassembled, inspected, modified, reassembled, checked out and reserviced, as were most other systems onboard. The work includes the installation of the Multifunction Electronic Display Subsystem (MEDS) - a state-of-the-art “glass cockpit.”

  13. Discovery of Charm

    DOE R&D Accomplishments Database

    Goldhaber, G.

    1984-11-01

    In my talk I will cover the period 1973 to 1976 which saw the discoveries of the J/psi and psi' resonances and most of the Psion spectroscopy, the tau lepton and the D0030099,D0015599 charmed meson doublet. Occasionally I will refer briefly to more recent results. Since this conference is on the history of the weak-interactions I will deal primarily with the properties of naked charm and in particular the weakly decaying doublet of charmed mesons. Most of the discoveries I will mention were made with the SLAC-LBL Magnetic Detector or MARK I which we operated at SPEAR from 1973 to 1976.

  14. Metabolic mechanism of mannan in a ruminal bacterium, Ruminococcus albus, involving two mannoside phosphorylases and cellobiose 2-epimerase: discovery of a new carbohydrate phosphorylase, β-1,4-mannooligosaccharide phosphorylase.

    PubMed

    Kawahara, Ryosuke; Saburi, Wataru; Odaka, Rei; Taguchi, Hidenori; Ito, Shigeaki; Mori, Haruhide; Matsui, Hirokazu

    2012-12-07

    Ruminococcus albus is a typical ruminal bacterium digesting cellulose and hemicellulose. Cellobiose 2-epimerase (CE; EC 5.1.3.11), which converts cellobiose to 4-O-β-D-glucosyl-D-mannose, is a particularly unique enzyme in R. albus, but its physiological function is unclear. Recently, a new metabolic pathway of mannan involving CE was postulated for another CE-producing bacterium, Bacteroides fragilis. In this pathway, β-1,4-mannobiose is epimerized to 4-O-β-D-mannosyl-D-glucose (Man-Glc) by CE, and Man-Glc is phosphorolyzed to α-D-mannosyl 1-phosphate (Man1P) and D-glucose by Man-Glc phosphorylase (MP; EC 2.4.1.281). Ruminococcus albus NE1 showed intracellular MP activity, and two MP isozymes, RaMP1 and RaMP2, were obtained from the cell-free extract. These enzymes were highly specific for the mannosyl residue at the non-reducing end of the substrate and catalyzed the phosphorolysis and synthesis of Man-Glc through a sequential Bi Bi mechanism. In a synthetic reaction, RaMP1 showed high activity only toward D-glucose and 6-deoxy-D-glucose in the presence of Man1P, whereas RaMP2 showed acceptor specificity significantly different from RaMP1. RaMP2 acted on D-glucose derivatives at the C2- and C3-positions, including deoxy- and deoxyfluoro-analogues and epimers, but not on those substituted at the C6-position. Furthermore, RaMP2 had high synthetic activity toward the following oligosaccharides: β-linked glucobioses, maltose, N,N'-diacetylchitobiose, and β-1,4-mannooligosaccharides. Particularly, β-1,4-mannooligosaccharides served as significantly better acceptor substrates for RaMP2 than D-glucose. In the phosphorolytic reactions, RaMP2 had weak activity toward β-1,4-mannobiose but efficiently degraded β-1,4-mannooligosaccharides longer than β-1,4-mannobiose. Consequently, RaMP2 is thought to catalyze the phosphorolysis of β-1,4-mannooligosaccharides longer than β-1,4-mannobiose to produce Man1P and β-1,4-mannobiose.

  15. Discovery in translation: near-infrared fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Sevick-Muraca, Eva M.

    2012-01-01

    When translating new imaging modalities into the clinic, one can expect new discoveries. Owing to the high photon count rates, near-infrared fluorescence (NIRF) offers exquisite sensitivity and high temporal resolution that enable new insights into human disorders. Herein, the physics of NIRF are highlighted and compared to those involved in nuclear medicine techniques. The initial application of investigational NIRF involving characterization of the lymphatics in humans and animal models of human disease yields discoveries not otherwise attainable with conventional imaging.

  16. Discovery Education: A Definition.

    ERIC Educational Resources Information Center

    Wilson, Harold C.

    2002-01-01

    Discovery Education is based on the writings of Henry David Thoreau, an early champion of experiential learning. After 2 months of preparation, 10th-grade students spent 4 days in the wilderness reenacting a piece of history, such as the Lewis and Clark Expedition. The interdisciplinary approach always included journal-writing. Students gained…

  17. The Discovery of America

    ERIC Educational Resources Information Center

    Martin, Paul S.

    1973-01-01

    Discusses a model for explaining the spread of human population explosion on North American continent since its discovery 12,000 years ago. The model may help to map the spread of Homo sapiens throughout the New World by using the extinction chronology of the Pleistocene megafauna. (Author/PS)

  18. MR1 discovery.

    PubMed

    Hashimoto, Keiichiro

    2016-08-01

    The moment of MR1 discovery is described. The MR1 gene is the first and the last reported human MHC-related gene intentionally isolated from the human genome composed of three billion base pairs. Evolutionary considerations formed the basis of its isolation. Some details surrounding the moment and some retrospective descriptions with various kinds of encounters are also included.

  19. Discovery forward nose cone

    NASA Image and Video Library

    2005-06-29

    S114-E-6194 (3 August 2005) --- This picture of the forward section of the Space Shuttle Discovery docked to the International Space Station was taken by Japan Aerospace Exploration Agency Astronaut Soichi Noguchi during the third and final spacewalk for the STS-114 mission. Both Noguchi and his crewmate Astronaut Stephen K. Robinson were equipped with digital still cameras on the spacewalks.

  20. Birds. Nature Discovery I.

    ERIC Educational Resources Information Center

    Stone, Sally F.

    The birds of New England and their particular habitats are explored in this guide which is part of a series of Nature Discovery publications. The materials are designed to directly supplement the natural science curricula and to complement other subject areas including social studies, language arts, music, and art. The program is designed for…

  1. Historian's Discovery of Childhood

    ERIC Educational Resources Information Center

    Frijhoff, Willem

    2012-01-01

    The "discovery of childhood" is a tricky notion because childhood is as much a fact of a biological and psychological nature as a cultural notion that through the centuries has been the object of changing perceptions, definitions, and images. Children barely speak in history; virtually everything we know about them is mediated by adults. Then how…

  2. The Discovery of America

    ERIC Educational Resources Information Center

    Martin, Paul S.

    1973-01-01

    Discusses a model for explaining the spread of human population explosion on North American continent since its discovery 12,000 years ago. The model may help to map the spread of Homo sapiens throughout the New World by using the extinction chronology of the Pleistocene megafauna. (Author/PS)

  3. The Discovery Way

    ERIC Educational Resources Information Center

    Hamlin, Theresa

    2005-01-01

    At the Center for Discovery (The Center), a private, non-profit agency 80 miles northwest of New York City in the Catskill Mountains, children are growing and learning at their own pace, in their own way, with careful attention focused on communication and social/emotional development. Children with autism are being educated to be social beings,…

  4. Discovery Education: A Definition.

    ERIC Educational Resources Information Center

    Wilson, Harold C.

    2002-01-01

    Discovery Education is based on the writings of Henry David Thoreau, an early champion of experiential learning. After 2 months of preparation, 10th-grade students spent 4 days in the wilderness reenacting a piece of history, such as the Lewis and Clark Expedition. The interdisciplinary approach always included journal-writing. Students gained…

  5. Knowledge Discovery in Databases.

    ERIC Educational Resources Information Center

    Norton, M. Jay

    1999-01-01

    Knowledge discovery in databases (KDD) revolves around the investigation and creation of knowledge, processes, algorithms, and mechanisms for retrieving knowledge from data collections. The article is an introductory overview of KDD. The rationale and environment of its development and applications are discussed. Issues related to database design…

  6. Scientific Discovery for All

    ERIC Educational Resources Information Center

    Zaikowski, Lori; Lichtman, Paul; Quarless, Duncan

    2007-01-01

    The scientific discovery process comes alive for 70 minority students each year at Uniondale High School in New York where students have won top awards for "in-house" projects. Uniondale High School is in a middle-income school district where over 95% of students are from minority groups. Founded in 2000, the Uniondale High School Research Program…

  7. Knowledge Discovery in Databases.

    ERIC Educational Resources Information Center

    Norton, M. Jay

    1999-01-01

    Knowledge discovery in databases (KDD) revolves around the investigation and creation of knowledge, processes, algorithms, and mechanisms for retrieving knowledge from data collections. The article is an introductory overview of KDD. The rationale and environment of its development and applications are discussed. Issues related to database design…

  8. The Discovery Way

    ERIC Educational Resources Information Center

    Hamlin, Theresa

    2005-01-01

    At the Center for Discovery (The Center), a private, non-profit agency 80 miles northwest of New York City in the Catskill Mountains, children are growing and learning at their own pace, in their own way, with careful attention focused on communication and social/emotional development. Children with autism are being educated to be social beings,…

  9. Birds. Nature Discovery I.

    ERIC Educational Resources Information Center

    Stone, Sally F.

    The birds of New England and their particular habitats are explored in this guide which is part of a series of Nature Discovery publications. The materials are designed to directly supplement the natural science curricula and to complement other subject areas including social studies, language arts, music, and art. The program is designed for…

  10. Historian's Discovery of Childhood

    ERIC Educational Resources Information Center

    Frijhoff, Willem

    2012-01-01

    The "discovery of childhood" is a tricky notion because childhood is as much a fact of a biological and psychological nature as a cultural notion that through the centuries has been the object of changing perceptions, definitions, and images. Children barely speak in history; virtually everything we know about them is mediated by adults. Then how…

  11. A Passport to Discovery

    ERIC Educational Resources Information Center

    Taylor, Ellen

    2004-01-01

    Have you ever had an experience too good to be true; one that you could not wait to share with your friends? In this article, the author describes such an experience that she had last summer when she was a part of the "Passport to Discovery" tour offered by CRIZMAC Art and Cultural Education Materials, Inc., and led by founder Stevie Mack and…

  12. Scientific Discovery for All

    ERIC Educational Resources Information Center

    Zaikowski, Lori; Lichtman, Paul; Quarless, Duncan

    2007-01-01

    The scientific discovery process comes alive for 70 minority students each year at Uniondale High School in New York where students have won top awards for "in-house" projects. Uniondale High School is in a middle-income school district where over 95% of students are from minority groups. Founded in 2000, the Uniondale High School Research Program…

  13. Metabolic Disturbances in Diseases with Neurological Involvement

    PubMed Central

    Duarte, João M. N.; Schuck, Patrícia F.; Wenk, Gary L.; Ferreira, Gustavo C.

    2014-01-01

    Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alterations, exogenous toxins or buildup of toxic metabolites. In this review we shall discuss some metabolic alterations related to the pathophysiology of diseases with neurological involvement and aging process. These findings may help identifying early disease biomarkers and lead to more effective therapies to improve the quality of life of the patients affected by these devastating illnesses. PMID:25110608

  14. Discovery and preclinical development of new antibiotics.

    PubMed

    Hughes, Diarmaid; Karlén, Anders

    2014-05-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted.

  15. Recent Discoveries and Bible Translation.

    ERIC Educational Resources Information Center

    Harrelson, Walter

    1990-01-01

    Discusses recent discoveries for "Bible" translation with a focus on the "Dead Sea Scrolls." Examines recent discoveries that provide direct support for alternative reading of biblical passages and those discoveries that have contributed additional insight to knowledge of cultural practices, especially legal and religious…

  16. The Discovery Method in Training.

    ERIC Educational Resources Information Center

    Belbin, R. M.

    In the form of a discussion between faceless people, this booklet concerns discovery learning and its advantages. Subjects covered in the discussions are: Introducing the Discovery Method; An Experiment with British Railways; The OECD Research Projects in U.S.A., Austria, and Sweden; How the Discovery Method Differs from Other Methods; Discovery…

  17. The Discovery Method in Training.

    ERIC Educational Resources Information Center

    Belbin, R. M.

    In the form of a discussion between faceless people, this booklet concerns discovery learning and its advantages. Subjects covered in the discussions are: Introducing the Discovery Method; An Experiment with British Railways; The OECD Research Projects in U.S.A., Austria, and Sweden; How the Discovery Method Differs from Other Methods; Discovery…

  18. Challenges of Antibacterial Discovery

    PubMed Central

    Silver, Lynn L.

    2011-01-01

    Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort. PMID:21233508

  19. Chronicles in drug discovery.

    PubMed

    Davies, Shelley L; Moral, Maria Angels; Bozzo, Jordi

    2007-03-01

    Chronicles in Drug Discovery features special interest reports on advances in drug discovery. This month we highlight agents that target and deplete immunosuppressive regulatory T cells, which are produced by tumor cells to hinder innate immunity against, or chemotherapies targeting, tumor-associated antigens. Antiviral treatments for respiratory syncytial virus, a severe and prevalent infection in children, are limited due to their side effect profiles and cost. New strategies currently under clinical development include monoclonal antibodies, siRNAs, vaccines and oral small molecule inhibitors. Recent therapeutic lines for Huntington's disease include gene therapies that target the mutated human huntingtin gene or deliver neuroprotective growth factors and cellular transplantation in apoptotic regions of the brain. Finally, we highlight the antiinflammatory and antinociceptive properties of new compounds targeting the somatostatin receptor subtype sst4, which warrant further study for their potential application as clinical analgesics.

  20. [Halogens: discoveries of pharmacists].

    PubMed

    Rabiant, J

    2008-01-01

    The discovery of four halogens is due to pharmacists. Chlorine was isolated by Carl Wilhem Scheele, a Swedish who was first an assistant to a pharmacist, then a pharmacist himself. Bernard Courtois, a pharmacist under the First Empire, the son of a saltpetre worker isolated iodine in I811, after a modification of the ancestral production protocol of potassium nitrate, which is the major component of the gunpowder: he replaced wood ashes by varech ashes which are less expensive. Antoine Jerôme Balard was still an assistant in chemistry and physics when he discovered bromine in the residues of the salt marshes. He became soon after a pharmacist and started a famous career as then he became Professor in the College de France and General Inspector of Higher Education. The last halogen: fluorine was isolated by Henri Moissan who received the Nobel Prize of Chemistry. The discovery will be the subject of our next communication.

  1. Discovery of charm

    SciTech Connect

    Goldhaber, G.

    1984-11-01

    In my talk I will cover the period 1973 to 1976 which saw the discoveries of the J/psi and psi' resonances and most of the Psion spectroscopy, the tau lepton and the D/sup 0/,D/sup +/ charmed meson doublet. Occasionally I will refer briefly to more recent results. Since this conference is on the history of the weak-interactions I will deal primarily with the properties of naked charm and in particular the weakly decaying doublet of charmed mesons. Most of the discoveries I will mention were made with the SLAC-LBL Magnetic Detector or MARK I which we operated at SPEAR from 1973 to 1976. 27 references.

  2. Discovery with FAST

    NASA Astrophysics Data System (ADS)

    Wilkinson, P.

    2016-02-01

    FAST offers "transformational" performance well-suited to finding new phenomena - one of which might be polarised spectral transients. But discoveries will only be made if "the system" provides its users with the necessary opportunities. In addition to designing in as much observational flexibility as possible, FAST should be operated with a philosophy which maximises its "human bandwidth". This band includes the astronomers of tomorrow - many of whom not have yet started school or even been born.

  3. Discovery management workshop

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Two dozen participants assembled under the direction of the NASA Solar System Exploration Division (SEED) April 13-15, 1993. Participants supported the goals of cheaper and faster solar system exploration. The workshop concluded that the Discovery Program concept and goals are viable. Management concerns are articulated in the final report. Appendix A includes lists of participants in alphabetical order, by functional area, and by organization type. Appendix B includes the agenda for the meeting.

  4. Asteroid Discovery in History

    NASA Astrophysics Data System (ADS)

    Williams, G.; Murdin, P.

    2001-10-01

    The discovery of five of the major planets (other than Earth) in the solar system is lost to antiquity. With the acceptance of Copernicus' heliocentric model for the solar system an apparent anomaly in the spacing of the planets was noted. JOHANNES KEPLER believed that the gap between Mars and Jupiter was too large in proportion to the gaps between other pairs of neighboring planets. He concluded...

  5. Discovery concepts for Mars

    NASA Technical Reports Server (NTRS)

    Luhmann, J. G.; Russell, C. T.; Brace, L. H.; Nagy, A. F.; Jakosky, B. M.; Barth, C. A.; Waite, J. H.

    1992-01-01

    Two focused Mars missions that would fit within the guidelines for the proposed Discovery line are discussed. The first mission would deal with the issue of the escape of the atmosphere (Mars') to space. A complete understanding of this topic is crucial to deciphering the evolution of the atmosphere, climate change, and volatile inventories. The second mission concerns the investigation of remanent magnetization of the crust and its relationship to the ionosphere and the atmosphere.

  6. Discovery Systems for Manufacturing

    DTIC Science & Technology

    1994-01-01

    the backbone of most of the materials discovery activities we pursue. We call the internal structure of a qualitative model an envisionment . A simple... envisionment (discussed in detail in the next chapter) from the polymer curing domain that is illustrated in figure 1-7. The initial conditions are...TSC "fires" IF-THEN rules which the initial conditions enable, building an envisonment. A stylized envisionment for the immunology knowledge base looks

  7. The language of discovery

    PubMed Central

    Souba, Wiley

    2011-01-01

    Discovery, as a public attribution, and discovering, the act of conducting research, are experiences that entail “languaging” the unknown. This distinguishing property of language ‐ its ability to bring forth, out of the unspoken realm, new knowledge, original ideas, and novel thinking – is essential to the discovery process. In sharing their ideas and views, scientists create co‐negotiated linguistic distinctions that prompt the revision of established mental maps and the adoption of new ones. While scientific mastery entails command of the conversational domain unique to a specific discipline, there is an emerging conversational domain that must be mastered that goes beyond the language unique to any particular specialty. Mastery of this new conversational domain gives researchers access to their hidden mental maps that limit their ways of thinking about and doing science. The most effective scientists use language to recontextualize their approach to problem‐solving, which triggers new insights (previously unavailable) that result in new discoveries. While language is not a replacement for intuition and other means of knowing, when we try to understand what’s outside of language we have to use language to do so. PMID:21688238

  8. The language of discovery.

    PubMed

    Souba, Wiley

    2011-06-17

    Discovery, as a public attribution, and discovering, the act of conducting research, are experiences that entail "languaging" the unknown. This distinguishing property of language - its ability to bring forth, out of the unspoken realm, new knowledge, original ideas, and novel thinking - is essential to the discovery process. In sharing their ideas and views, scientists create co-negotiated linguistic distinctions that prompt the revision of established mental maps and the adoption of new ones. While scientific mastery entails command of the conversational domain unique to a specific discipline, there is an emerging conversational domain that must be mastered that goes beyond the language unique to any particular specialty. Mastery of this new conversational domain gives researchers access to their hidden mental maps that limit their ways of thinking about and doing science. The most effective scientists use language to recontextualize their approach to problem-solving, which triggers new insights (previously unavailable) that result in new discoveries. While language is not a replacement for intuition and other means of knowing, when we try to understand what's outside of language we have to use language to do so.

  9. Component architecture in drug discovery informatics.

    PubMed

    Smith, Peter M

    2002-05-01

    This paper reviews the characteristics of a new model of computing that has been spurred on by the Internet, known as Netcentric computing. Developments in this model led to distributed component architectures, which, although not new ideas, are now realizable with modern tools such as Enterprise Java. The application of this approach to scientific computing, particularly in pharmaceutical discovery research, is discussed and highlighted by a particular case involving the management of biological assay data.

  10. Science of the science, drug discovery and artificial neural networks.

    PubMed

    Patel, Jigneshkumar

    2013-03-01

    Drug discovery process many times encounters complex problems, which may be difficult to solve by human intelligence. Artificial Neural Networks (ANNs) are one of the Artificial Intelligence (AI) technologies used for solving such complex problems. ANNs are widely used for primary virtual screening of compounds, quantitative structure activity relationship studies, receptor modeling, formulation development, pharmacokinetics and in all other processes involving complex mathematical modeling. Despite having such advanced technologies and enough understanding of biological systems, drug discovery is still a lengthy, expensive, difficult and inefficient process with low rate of new successful therapeutic discovery. In this paper, author has discussed the drug discovery science and ANN from very basic angle, which may be helpful to understand the application of ANN for drug discovery to improve efficiency.

  11. On Involvement.

    ERIC Educational Resources Information Center

    Greene, Michael B.

    Involvement Ratings In Settings (IRIS), a multi-dimensional non-verbal scale of involvement adaptable to a time-sampling method of data collection, was constructed with the aid of the videotapes of second-grade Follow Through classrooms made by CCEP. Scales were defined through observations of involved and alienated behavior, and the IRIS was…

  12. On Involvement.

    ERIC Educational Resources Information Center

    Greene, Michael B.

    Involvement Ratings In Settings (IRIS), a multi-dimensional non-verbal scale of involvement adaptable to a time-sampling method of data collection, was constructed with the aid of the videotapes of second-grade Follow Through classrooms made by CCEP. Scales were defined through observations of involved and alienated behavior, and the IRIS was…

  13. From crystal to compound: structure-based antimalarial drug discovery.

    PubMed

    Drinkwater, Nyssa; McGowan, Sheena

    2014-08-01

    Despite a century of control and eradication campaigns, malaria remains one of the world's most devastating diseases. Our once-powerful therapeutic weapons are losing the war against the Plasmodium parasite, whose ability to rapidly develop and spread drug resistance hamper past and present malaria-control efforts. Finding new and effective treatments for malaria is now a top global health priority, fuelling an increase in funding and promoting open-source collaborations between researchers and pharmaceutical consortia around the world. The result of this is rapid advances in drug discovery approaches and technologies, with three major methods for antimalarial drug development emerging: (i) chemistry-based, (ii) target-based, and (iii) cell-based. Common to all three of these approaches is the unique ability of structural biology to inform and accelerate drug development. Where possible, SBDD (structure-based drug discovery) is a foundation for antimalarial drug development programmes, and has been invaluable to the development of a number of current pre-clinical and clinical candidates. However, as we expand our understanding of the malarial life cycle and mechanisms of resistance development, SBDD as a field must continue to evolve in order to develop compounds that adhere to the ideal characteristics for novel antimalarial therapeutics and to avoid high attrition rates pre- and post-clinic. In the present review, we aim to examine the contribution that SBDD has made to current antimalarial drug development efforts, covering hit discovery to lead optimization and prevention of parasite resistance. Finally, the potential for structural biology, particularly high-throughput structural genomics programmes, to identify future targets for drug discovery are discussed.

  14. Computational approaches for drug discovery.

    PubMed

    Hung, Che-Lun; Chen, Chi-Chun

    2014-09-01

    Cellular proteins are the mediators of multiple organism functions being involved in physiological mechanisms and disease. By discovering lead compounds that affect the function of target proteins, the target diseases or physiological mechanisms can be modulated. Based on knowledge of the ligand-receptor interaction, the chemical structures of leads can be modified to improve efficacy, selectivity and reduce side effects. One rational drug design technology, which enables drug discovery based on knowledge of target structures, functional properties and mechanisms, is computer-aided drug design (CADD). The application of CADD can be cost-effective using experiments to compare predicted and actual drug activity, the results from which can used iteratively to improve compound properties. The two major CADD-based approaches are structure-based drug design, where protein structures are required, and ligand-based drug design, where ligand and ligand activities can be used to design compounds interacting with the protein structure. Approaches in structure-based drug design include docking, de novo design, fragment-based drug discovery and structure-based pharmacophore modeling. Approaches in ligand-based drug design include quantitative structure-affinity relationship and pharmacophore modeling based on ligand properties. Based on whether the structure of the receptor and its interaction with the ligand are known, different design strategies can be seed. After lead compounds are generated, the rule of five can be used to assess whether these have drug-like properties. Several quality validation methods, such as cost function analysis, Fisher's cross-validation analysis and goodness of hit test, can be used to estimate the metrics of different drug design strategies. To further improve CADD performance, multi-computers and graphics processing units may be applied to reduce costs. © 2014 Wiley Periodicals, Inc.

  15. 14 CFR 406.143 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... after a complaint has been filed. (b) Methods of discovery. The following methods of discovery are... discovery methods permitted under this section; or (4) The method or scope of discovery requested by the... method of discovery; or (3) Limit the scope of discovery or preclude any inquiry into certain...

  16. The Discovery Channel Telescope

    NASA Astrophysics Data System (ADS)

    Millis, R. L.; Dunham, E. W.; Sebring, T. A.; Smith, B. W.; de Kock, M.; Wiecha, O.

    2004-11-01

    The Discovery Channel Telescope (DCT) is a 4.2-m telescope to be built at a new site near Happy Jack, Arizona. The DCT features a large prime focus mosaic CCD camera with a 2-degree-diameter field of view especially designed for surveys of KBOs, Centaurs, NEAs and other moving or time-variable targets. The telescope can be switched quickly to a Ritchey-Chretien configuration for optical/IR spectroscopy or near-IR imaging. This flexibility allows timely follow-up physical studies of high priority objects discovered in survey mode. The ULE (ultra-low-expansion) meniscus primary and secondary mirror blanks for the telescope are currently in fabrication by Corning Glass. Goodrich Aerospace, Vertex RSI, M3 Engineering and Technology Corp., and e2v Technologies have recently completed in-depth conceptual design studies of the optics, mount, enclosure, and mosaic focal plane, respectively. The results of these studies were subjected to a formal design review in July, 2004. Site testing at the 7760-ft altitude Happy Jack site began in 2001. Differential image motion observations from 117 nights since January 1, 2003 gave median seeing of 0.84 arcsec FWHM, and the average of the first quartile was 0.62 arcsec. The National Environmental Policy Act (NEPA) process for securing long-term access to this site on the Coconino National Forest is nearing completion and ground breaking is expected in the spring of 2005. The Discovery Channel Telescope is a project of the Lowell Observatory with major financial support from Discovery Communications, Inc. (DCI). DCI plans ongoing television programming featuring the construction of the telescope and the research ultimately undertaken with the DCT. An additional partner can be accommodated in the project. Interested parties should contact the lead author.

  17. Computational biology for cardiovascular biomarker discovery.

    PubMed

    Azuaje, Francisco; Devaux, Yvan; Wagner, Daniel

    2009-07-01

    Computational biology is essential in the process of translating biological knowledge into clinical practice, as well as in the understanding of biological phenomena based on the resources and technologies originating from the clinical environment. One such key contribution of computational biology is the discovery of biomarkers for predicting clinical outcomes using 'omic' information. This process involves the predictive modelling and integration of different types of data and knowledge for screening, diagnostic or prognostic purposes. Moreover, this requires the design and combination of different methodologies based on statistical analysis and machine learning. This article introduces key computational approaches and applications to biomarker discovery based on different types of 'omic' data. Although we emphasize applications in cardiovascular research, the computational requirements and advances discussed here are also relevant to other domains. We will start by introducing some of the contributions of computational biology to translational research, followed by an overview of methods and technologies used for the identification of biomarkers with predictive or classification value. The main types of 'omic' approaches to biomarker discovery will be presented with specific examples from cardiovascular research. This will include a review of computational methodologies for single-source and integrative data applications. Major computational methods for model evaluation will be described together with recommendations for reporting models and results. We will present recent advances in cardiovascular biomarker discovery based on the combination of gene expression and functional network analyses. The review will conclude with a discussion of key challenges for computational biology, including perspectives from the biosciences and clinical areas.

  18. Drug discovery in jeopardy

    PubMed Central

    Cuatrecasas, Pedro

    2006-01-01

    Despite striking advances in the biomedical sciences, the flow of new drugs has slowed to a trickle, impairing therapeutic advances as well as the commercial success of drug companies. Reduced productivity in the drug industry is caused mainly by corporate policies that discourage innovation. This is compounded by various consequences of mega-mergers, the obsession for blockbuster drugs, the shift of control of research from scientists to marketers, the need for fast sales growth, and the discontinuation of development compounds for nontechnical reasons. Lessons from the past indicate that these problems can be overcome, and herein, new and improved directions for drug discovery are suggested. PMID:17080187

  19. Research Discoveries After Kubin

    PubMed Central

    Vensko, Nancy W.; Ferguson, Steven M.

    2010-01-01

    This paper will discuss commercializing discoveries made at research organizations, particularly with a view to the In re Kubin case, decided April 3, 2009, by the Federal Circuit. Here, the existence of a general method of isolating DNA molecules was held to be relevant to the question whether the DNA molecules themselves would have been obvious under § 103 of the patent act. How are DNA inventions patented anyway? What does it take for academic research to reach patients? How might the decision of In re Kubin effect research commercialization and technology transfer? PMID:20543971

  20. Drug discovery: new models for industry-academic partnerships.

    PubMed

    Tralau-Stewart, Cathy J; Wyatt, Colin A; Kleyn, Dominique E; Ayad, Alex

    2009-01-01

    The re-focusing of pharmaceutical industry research away from early discovery activities is stimulating the development of novel models of drug discovery, notably involving academia as a 'front end'. In this article the authors explore the drivers of change, the role of new entrants (universities with specialised core facilities) and novel partnership models. If they are to be sustainable and deliver, these new models must be flexible and properly funded by industry or public funding, rewarding all partners for contributions. The introduction of an industry-like process and experienced management teams signals a revolution in discovery that benefits society by improving the value gained from publicly funded research.

  1. Causality discovery technology

    NASA Astrophysics Data System (ADS)

    Chen, M.; Ertl, T.; Jirotka, M.; Trefethen, A.; Schmidt, A.; Coecke, B.; Bañares-Alcántara, R.

    2012-11-01

    Causality is the fabric of our dynamic world. We all make frequent attempts to reason causation relationships of everyday events (e.g., what was the cause of my headache, or what has upset Alice?). We attempt to manage causality all the time through planning and scheduling. The greatest scientific discoveries are usually about causality (e.g., Newton found the cause for an apple to fall, and Darwin discovered natural selection). Meanwhile, we continue to seek a comprehensive understanding about the causes of numerous complex phenomena, such as social divisions, economic crisis, global warming, home-grown terrorism, etc. Humans analyse and reason causality based on observation, experimentation and acquired a priori knowledge. Today's technologies enable us to make observations and carry out experiments in an unprecedented scale that has created data mountains everywhere. Whereas there are exciting opportunities to discover new causation relationships, there are also unparalleled challenges to benefit from such data mountains. In this article, we present a case for developing a new piece of ICT, called Causality Discovery Technology. We reason about the necessity, feasibility and potential impact of such a technology.

  2. Automated Supernova Discovery (Abstract)

    NASA Astrophysics Data System (ADS)

    Post, R. S.

    2015-12-01

    (Abstract only) We are developing a system of robotic telescopes for automatic recognition of Supernovas as well as other transient events in collaboration with the Puckett Supernova Search Team. At the SAS2014 meeting, the discovery program, SNARE, was first described. Since then, it has been continuously improved to handle searches under a wide variety of atmospheric conditions. Currently, two telescopes are used to build a reference library while searching for PSN with a partial library. Since data is taken every night without clouds, we must deal with varying atmospheric and high background illumination from the moon. Software is configured to identify a PSN, reshoot for verification with options to change the run plan to acquire photometric or spectrographic data. The telescopes are 24-inch CDK24, with Alta U230 cameras, one in CA and one in NM. Images and run plans are sent between sites so the CA telescope can search while photometry is done in NM. Our goal is to find bright PSNs with magnitude 17.5 or less which is the limit of our planned spectroscopy. We present results from our first automated PSN discoveries and plans for PSN data acquisition.

  3. Expanding horizons in complement drug discovery: challenges and emerging strategies.

    PubMed

    Harris, Claire L

    2017-10-06

    The complement system is best known for its role in innate immunity, providing a first line of defence against infection, maintaining tissue homeostasis by flagging apoptotic cells and debris for removal, and orchestrating crosstalk between adaptive and innate immunity. In a growing number of diseases, complement is known to drive pathogenesis or to contribute as an inflammatory amplifier of a disease trigger. Association of complement with common and devastating diseases has driven an upsurge in complement drug discovery, but despite a wealth of knowledge in the complexities of the cascade, and many decades of effort, very few drugs have progressed to late-stage clinical studies. The reasons for this are becoming clear with difficulties including high target concentration and turnover, lack of clarity around disease mechanism and unwanted side effects. Lessons learnt from drugs which are either approved, or are currently in late-stage development, or have failed and dropped off the drug development landscape, have been invaluable to drive a new generation of innovative drugs which are progressing through clinical development. In this review, the challenges associated with complement drug discovery are discussed and the current drug development landscape is reviewed. The latest approaches to improve drug characteristics are explored and those agents which employ these technologies to improve accessibility to patients are highlighted.

  4. Discovery and Classification in Astronomy

    NASA Astrophysics Data System (ADS)

    Dick, Steven J.

    2012-01-01

    Three decades after Martin Harwit's pioneering Cosmic Discovery (1981), and following on the recent IAU Symposium "Accelerating the Rate of Astronomical Discovery,” we have revisited the problem of discovery in astronomy, emphasizing new classes of objects. 82 such classes have been identified and analyzed, including 22 in the realm of the planets, 36 in the realm of the stars, and 24 in the realm of the galaxies. We find an extended structure of discovery, consisting of detection, interpretation and understanding, each with its own nuances and a microstructure including conceptual, technological and social roles. This is true with a remarkable degree of consistency over the last 400 years of telescopic astronomy, ranging from Galileo's discovery of satellites, planetary rings and star clusters, to the discovery of quasars and pulsars. Telescopes have served as "engines of discovery” in several ways, ranging from telescope size and sensitivity (planetary nebulae and spiral galaxies), to specialized detectors (TNOs) and the opening of the electromagnetic spectrum for astronomy (pulsars, pulsar planets, and most active galaxies). A few classes (radiation belts, the solar wind and cosmic rays), were initially discovered without the telescope. Classification also plays an important role in discovery. While it might seem that classification marks the end of discovery, or a post-discovery phase, in fact it often marks the beginning, even a pre-discovery phase. Nowhere is this more clearly seen than in the classification of stellar spectra, long before dwarfs, giants and supergiants were known, or their evolutionary sequence recognized. Classification may also be part of a post-discovery phase, as in the MK system of stellar classification, constructed after the discovery of stellar luminosity classes. Some classes are declared rather than discovered, as in the case of gas and ice giant planets, and, infamously, Pluto as a dwarf planet.

  5. Discovery STS-133 Mission Landing

    NASA Image and Video Library

    2011-03-09

    Crowds start to gather at the Shuttle Landing Facility (SLF) in preparation for the landing of the space shuttle Discovery, Wednesday, March 9, 2011, at Kennedy Space Center in Cape Canaveral, Fla. This was Discovery's final flight. Discovery flew 39 missions, spent 365 days in space, orbited Earth 5,830 times and traveled 148,221,675 miles. Photo credit: (NASA/Bill Ingalls)

  6. Discovery Planetary Mission Operations Concepts

    NASA Technical Reports Server (NTRS)

    Coffin, R.

    1994-01-01

    The NASA Discovery Program of small planetary missions will provide opportunities to continue scientific exploration of the solar system in today's cost-constrained environment. Using a multidisciplinary team, JPL has developed plans to provide mission operations within the financial parameters established by the Discovery Program. This paper describes experiences and methods that show promise of allowing the Discovery Missions to operate within the program cost constraints while maintaining low mission risk, high data quality, and reponsive operations.

  7. Family Involvement.

    ERIC Educational Resources Information Center

    Liontos, Lynn Balster

    1992-01-01

    Family involvement in schools will work only when perceived as an enlarged concept focusing on all children, including those from at-risk families. Each publication reviewed here is specifically concerned with family involvement strategies concerned with all children or targeted at primarily high risk students. Susan McAllister Swap looks at three…

  8. Optogenetics enlightens neuroscience drug discovery.

    PubMed

    Song, Chenchen; Knöpfel, Thomas

    2016-02-01

    Optogenetics - the use of light and genetics to manipulate and monitor the activities of defined cell populations - has already had a transformative impact on basic neuroscience research. Now, the conceptual and methodological advances associated with optogenetic approaches are providing fresh momentum to neuroscience drug discovery, particularly in areas that are stalled on the concept of 'fixing the brain chemistry'. Optogenetics is beginning to translate and transit into drug discovery in several key domains, including target discovery, high-throughput screening and novel therapeutic approaches to disease states. Here, we discuss the exciting potential of optogenetic technologies to transform neuroscience drug discovery.

  9. Bioanalysis in oncology drug discovery.

    PubMed

    Srinivas, Nuggehally R; Mullangi, Ramesh

    2015-01-01

    Bioanalysis is an important aspect of drug discovery process regardless of the chosen therapeutic area. There is a general misconception that bioanalysis is seldom important during the drug discovery process because there is no scrutiny of the data from a regulatory perspective. However, bioanalytical data gathered during the discovery stage enable several key decision(s) inclusive of termination of the program and/or creating adequate differentiation from the lead competitive molecules. The review covers various stage gate screens and experimental designs where bioanalytical data are extensively used for making an informed decision during the process of drug discovery.

  10. Hubble: 20 Years of Discovery

    NASA Image and Video Library

    Hubble's discoveries have revolutionized nearly all areas of current astronomical research from planetary science to cosmology. Actor and writer Brent Spiner narrates a visual journey back in time ...

  11. Rickets before the discovery of vitamin D

    PubMed Central

    O'Riordan, Jeffrey L H; Bijvoet, Olav L M

    2014-01-01

    The story of rickets leading to the discovery of vitamin D is an extraordinary tale, spread over many centuries and involving some remarkable characters with much speculation and a few mysteries, before reaching an exciting climax. It would be wrong to credit a single person as discovering rickets or being the first to describe its features, for reasons that will be set out here. Yet the emergence of the term ‘rickets' is as important as the discovery of vitamin D itself and the possible causes of its deficiency. It permitted identification of a hitherto ill-defined disease entity, typically occurring in infants and children. It also provided a way for deciding if features of diseases that had been described earlier in the history of medicine could be seen as the symptoms and signs of related conditions. PMID:24466409

  12. The Great East-Japan Earthquake and devastating tsunami: an update and lessons from the past Great Earthquakes in Japan since 1923.

    PubMed

    Ishigaki, Akemi; Higashi, Hikari; Sakamoto, Takako; Shibahara, Shigeki

    2013-04-01

    Japan has a long history of fighting against great earthquakes that cause structural damage/collapses, fires and/or tsunami. On March 11, 2011 at 14:46 (Friday), the Great East-Japan Earthquake (magnitude 9.0) attacked the Tohoku region (northeastern Japan), which includes Sendai City. The earthquake generated a devastating tsunami, leading to unprecedented disasters (~18,500 victims) in coastal areas of Iwate, Miyagi and Fukushima prefectures, despite the fact that people living in the Tohoku region are well trained for tsunami-evacuation procedures, with the mindset of "Tsunami, ten-den-ko." This code means that each person should evacuate individually upon an earthquake. Sharing this rule, children and parents can escape separately from schools, houses or workplaces, without worrying about each other. The concept of ten-den-ko (individual evacuation) is helpful for people living in coastal areas of earthquake-prone zones around the world. It is also important to construct safe evacuation centers, because the March 11(th) tsunami killed people who had evacuated to evacuation sites. We summarize the current conditions of people living in the disaster-stricken areas, including the consequences of the Fukushima nuclear accident. We also describe the disaster responses as the publisher of the Tohoku Journal of Experimental Medicine (TJEM), located in Sendai, with online support from Tokyo. In 1923, the Great Kanto Earthquake (magnitude 7.9) evoked a massive fire that destroyed large areas of Tokyo (~105,000 victims), including the print company for TJEM, but the Wistar Institute printed three TJEM issues in 1923 in Philadelphia. Mutual aid relationships should be established between distant cities to survive future disasters.

  13. The devastating Zhouqu storm-triggered debris flow of August 2010: Likely causes and possible trends in a future warming climate

    NASA Astrophysics Data System (ADS)

    Ren, Diandong

    2014-04-01

    On 8 August 2010 in the northwestern Chinese province of Gansu, a rainstorm-triggered debris flow devastated the small county of Zhouqu. A modeling study, using a new multiple-phase scalable and extensible geofluid model, suggests that the cause is an intersection of several events. These were a heavy rainstorm, not necessarily the result of global warming, which triggered the landslide and followed a drought that created surface cracks and crevasses; the geology of the region, notably the loess covering heavily weathered surface rock; and the bedrock damage, that deepened the surface crevasses inflicted by the 7.9 magnitude Wenchuan earthquake of 12 May 2008. Deforestation and topsoil erosion were critical contributors to the massive size of the debris flow. The modeling results underscore the urgency for a high-priority program of revegetation of Zhouqu County, without which the region will remain exposed to future disastrous, "progressive bulking" type landslides. Debris flows are more predictable types of landslides; consequently, a series of "pseudo climate change" model experiments of future extreme precipitation events are carried out using the Weather Research and Forecasting model, forced by temperature perturbations from an ensemble of climate models. In a possibly future warmer climate, extreme precipitation events are anticipated to be more severe, and this study has identified an atmospheric blocking pattern that might produce future extreme precipitation events in the peri-Tibetan Plateau (TP) area (located to the northeast of the TP). Importantly, observations from gravity field measuring satellites indicate that the larger geological environment of this region also is becoming increasingly unstable.

  14. Metagenomics and CAZyme Discovery.

    PubMed

    Kunath, Benoit J; Bremges, Andreas; Weimann, Aaron; McHardy, Alice C; Pope, Phillip B

    2017-01-01

    Microorganisms play a primary role in regulating biogeochemical cycles and are a valuable source of enzymes that have biotechnological applications, such as carbohydrate-active enzymes (CAZymes). However, the inability to culture the majority of microorganisms that exist in natural ecosystems using common culture-dependent techniques restricts access to potentially novel cellulolytic bacteria and beneficial enzymes. The development of molecular-based culture-independent methods such as metagenomics enables researchers to study microbial communities directly from environmental samples, and presents a platform from which enzymes of interest can be sourced. We outline key methodological stages that are required as well as describe specific protocols that are currently used for metagenomic projects dedicated to CAZyme discovery.

  15. Discovery with RSS retracted

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Rotating Service Structure has been retracted at Pad 39A. Discovery, the Space Shuttle for STS-82 Mission is ready for the launch of the second Hubble Space Telescope service mission. The payload consists of the Near Infrared Camera and Multi-Object Spectrometer (NICMOS) Which will be installed, the Fine Guidance Sensor #1 (FGS-1) and the Space Telescope Imaging Spectrograph (STIS) which will be installed. STS-82 will launch with a crew of seven at 3:54 a.m. February 11, 1997. The launch window is 65 minutes. The Mission Commander for STS-82 is Ken Bowersox. The purpose of the mission is to upgrade the scientific capabilities, service or replace aging components on the Telescope and provide a reboost to the optimum altitude.

  16. STS-51 Discovery launch

    NASA Image and Video Library

    1993-09-12

    STS051-S-108 (12 Sept. 1993) --- The Space Shuttle Discovery soars toward a nine-day stay in Earth-orbit to support the mission. Launch occurred at 7:45 a.m. (EDT) September 12, 1993. Note the diamond shock effect coming from the thrust of the three main engines. Onboard the shuttle were astronauts Frank L. Culbertson, Jr., William F. Readdy, Daniel W. Bursch, James H. Newman and Carl E. Walz, along with a number of payloads. The payloads included the Advanced Communications Technology Satellite (ACTS) with its Transfer Orbit Stage (TOS), the Orbiting Retrievable Far and Extreme Ultraviolet Spectrometer (ORFEUS) and its Shuttle Pallet Satellite (SPAS) carrier. This photograph was taken with a 35mm camera.

  17. Voyages of discovery.

    PubMed

    Allgrove, Jeremy

    2009-01-01

    The metabolism of calcium and bone is controlled by five principal hormones: parathyroid hormone, 1,25-dihydroxyvitamin D, calcitonin, parathyroid hormone-related peptide and fibroblast growth factor 23, some of which have been known for several decades and some of which have only recently been identified. The stories of discovery of these hormones have constituted a series of complex journeys which have been undertaken over the past century or so and none of which has yet been completed. The complexities of bone and calcium metabolism have been and remain, to many people, somewhat mysterious and a daunting task to understand. This book is designed to try to unravel those mysteries and present them in an interesting and comprehensible manner. Copyright (c) 2009 S. Karger AG, Basel.

  18. Drug discovery FAQs: workflows for answering multidomain drug discovery questions.

    PubMed

    Chichester, Christine; Digles, Daniela; Siebes, Ronald; Loizou, Antonis; Groth, Paul; Harland, Lee

    2015-04-01

    Modern data-driven drug discovery requires integrated resources to support decision-making and enable new discoveries. The Open PHACTS Discovery Platform (http://dev.openphacts.org) was built to address this requirement by focusing on drug discovery questions that are of high priority to the pharmaceutical industry. Although complex, most of these frequently asked questions (FAQs) revolve around the combination of data concerning compounds, targets, pathways and diseases. Computational drug discovery using workflow tools and the integrated resources of Open PHACTS can deliver answers to most of these questions. Here, we report on a selection of workflows used for solving these use cases and discuss some of the research challenges. The workflows are accessible online from myExperiment (http://www.myexperiment.org) and are available for reuse by the scientific community.

  19. Discovery and preclinical development of new antibiotics

    PubMed Central

    Karlén, Anders

    2014-01-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted. PMID:24646082

  20. Serendipity in anticancer drug discovery.

    PubMed

    Hargrave-Thomas, Emily; Yu, Bo; Reynisson, Jóhannes

    2012-01-10

    It was found that the discovery of 5.8% (84/1437) of all drugs on the market involved serendipity. Of these drugs, 31 (2.2%) were discovered following an incident in the laboratory and 53 (3.7%) were discovered in a clinical setting. In addition, 263 (18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total, 24.1% (347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is somewhat larger than for all drugs. The therapeutic field that has benefited the most from serendipity are central nervous system active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the diseases of the mind.

  1. Serendipity in anticancer drug discovery

    PubMed Central

    Hargrave-Thomas, Emily; Yu, Bo; Reynisson, Jóhannes

    2012-01-01

    It was found that the discovery of 5.8% (84/1437) of all drugs on the market involved serendipity. Of these drugs, 31 (2.2%) were discovered following an incident in the laboratory and 53 (3.7%) were discovered in a clinical setting. In addition, 263 (18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total, 24.1% (347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is somewhat larger than for all drugs. The therapeutic field that has benefited the most from serendipity are central nervous system active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the diseases of the mind. PMID:22247822

  2. Rontgen's Discovery of X Rays

    ERIC Educational Resources Information Center

    Thumm, Walter

    1975-01-01

    Relates the story of Wilhelm Conrad Rontgen and presents one view of the extent to which the discovery of the x-ray was an accident. Reconstructs the sequence of events that led to the discovery and includes photographs of the lab where he worked and replicas of apparatus used. (GS)

  3. Discovery Learning Strategies in English

    ERIC Educational Resources Information Center

    Singaravelu, G.

    2012-01-01

    The study substantiates that the effectiveness of Discovery Learning method in learning English Grammar for the learners at standard V. Discovery Learning is particularly beneficial for any student learning a second language. It promotes peer interaction and development of the language and the learning of concepts with content. Reichert and…

  4. Self Assessment and Discovery Learning

    ERIC Educational Resources Information Center

    McDonald, Betty

    2011-01-01

    Discovery learning in higher education has been reported to be effective in assisting learners to understand difficult concepts and retain long term information. This paper seeks to illustrate how one self assessment model may be used to demonstrate discovery learning in a collaborative atmosphere of students sharing and getting to know each…

  5. Discovery STS-133 Mission Landing

    NASA Image and Video Library

    2011-03-09

    Space Shuttle Discovery (STS-133) lands, Wednesday, March 9, 2011, at Kennedy Space Center in Cape Canaveral, Fla., completing its 39th and final flight. Since 1984, Discovery flew 39 missions, spent 365 days in space, orbited Earth 5,830 times and traveled 148,221,675 miles. Photo credit: (NASA/Bill Ingalls)

  6. Discovery STS-133 Mission Landing

    NASA Image and Video Library

    2011-03-09

    Space Shuttle Discovery (STS-133) is seen shortly after it landed, Wednesday, March 9, 2011, at Kennedy Space Center in Cape Canaveral, Fla., completing its 39th and final flight. Since 1984, Discovery flew 39 missions, spent 365 days in space, orbited Earth 5,830 times and traveled 148,221,675 miles. Photo credit: (NASA/Bill Ingalls)

  7. Discovery Reconceived: Product before Process

    ERIC Educational Resources Information Center

    Abrahamson, Dor

    2012-01-01

    Motivated by the question, "What exactly about a mathematical concept should students discover, when they study it via discovery learning?", I present and demonstrate an interpretation of discovery pedagogy that attempts to address its criticism. My approach hinges on decoupling the solution process from its resultant product. Whereas theories of…

  8. 14 CFR 13.220 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    .... (b) Methods of discovery. The following methods of discovery are permitted under this section... obtain the information through other discovery methods permitted under this section; or (4) The method or... or a determination of the method of discovery; or (3) Limit the scope of discovery or preclude...

  9. Politics, Chemistry, and the Discovery of Nuclear Fission

    NASA Astrophysics Data System (ADS)

    Wiesner, Emilie; Settle, Frank A., Jr.

    2001-07-01

    The discovery of fission is an interesting scientific saga involving the fundamentals of chemistry and physics. It is played out in the late 1930s on a European stage. Lise Meitner and Otto Hahn head a cast of characters that include scientific notables Fritz Strassmann, Otto Frisch, James Chadwick, Enrico Fermi, Ida Noddack, Irene Curie, and Neils Bohr. The plot includes the scientific method, the interdependence of chemistry and physics, the influence of external politics, and human frailty. The events surrounding this discovery did not allow the scientists involved to receive equal recognition. Fortunately, the passage of time and extensive historical research are restoring equality.

  10. Mining large heterogeneous data sets in drug discovery.

    PubMed

    Wild, David J

    2009-10-01

    Increasingly, effective drug discovery involves the searching and data mining of large volumes of information from many sources covering the domains of chemistry, biology and pharmacology amongst others. This has led to a proliferation of databases and data sources relevant to drug discovery. This paper provides a review of the publicly-available large-scale databases relevant to drug discovery, describes the kinds of data mining approaches that can be applied to them and discusses recent work in integrative data mining that looks for associations that pan multiple sources, including the use of Semantic Web techniques. The future of mining large data sets for drug discovery requires intelligent, semantic aggregation of information from all of the data sources described in this review, along with the application of advanced methods such as intelligent agents and inference engines in client applications.

  11. Prepared to react? Assessing the functional capacity of the primary health care system in rural Orissa, India to respond to the devastating flood of September 2008.

    PubMed

    Phalkey, Revati; Dash, Shisir R; Mukhopadhyay, Alok; Runge-Ranzinger, Silvia; Marx, Michael

    2012-01-01

    Early detection of an impending flood and the availability of countermeasures to deal with it can significantly reduce its health impacts. In developing countries like India, public primary health care facilities are frontline organizations that deal with disasters particularly in rural settings. For developing robust counter reacting systems evaluating preparedness capacities within existing systems becomes necessary. The objective of the study is to assess the functional capacity of the primary health care system in Jagatsinghpur district of rural Orissa in India to respond to the devastating flood of September 2008. An onsite survey was conducted in all 29 primary and secondary facilities in five rural blocks (administrative units) of Jagatsinghpur district in Orissa state. A pre-tested structured questionnaire was administered face to face in the facilities. The data was entered, processed and analyzed using STATA(®) 10. Data from our primary survey clearly shows that the healthcare facilities are ill prepared to handle the flood despite being faced by them annually. Basic utilities like electricity backup and essential medical supplies are lacking during floods. Lack of human resources along with missing standard operating procedures; pre-identified communication and incident command systems; effective leadership; and weak financial structures are the main hindering factors in mounting an adequate response to the floods. The 2008 flood challenged the primary curative and preventive health care services in Jagatsinghpur. Simple steps like developing facility specific preparedness plans which detail out standard operating procedures during floods and identify clear lines of command will go a long way in strengthening the response to future floods. Performance critiques provided by the grass roots workers, like this one, should be used for institutional learning and effective preparedness planning. Additionally each facility should maintain contingency funds for

  12. Prepared to react? Assessing the functional capacity of the primary health care system in rural Orissa, India to respond to the devastating flood of September 2008

    PubMed Central

    Phalkey, Revati; Dash, Shisir R.; Mukhopadhyay, Alok; Runge-Ranzinger, Silvia; Marx, Michael

    2012-01-01

    Background Early detection of an impending flood and the availability of countermeasures to deal with it can significantly reduce its health impacts. In developing countries like India, public primary health care facilities are frontline organizations that deal with disasters particularly in rural settings. For developing robust counter reacting systems evaluating preparedness capacities within existing systems becomes necessary. Objective The objective of the study is to assess the functional capacity of the primary health care system in Jagatsinghpur district of rural Orissa in India to respond to the devastating flood of September 2008. Methods An onsite survey was conducted in all 29 primary and secondary facilities in five rural blocks (administrative units) of Jagatsinghpur district in Orissa state. A pre-tested structured questionnaire was administered face to face in the facilities. The data was entered, processed and analyzed using STATA® 10. Results Data from our primary survey clearly shows that the healthcare facilities are ill prepared to handle the flood despite being faced by them annually. Basic utilities like electricity backup and essential medical supplies are lacking during floods. Lack of human resources along with missing standard operating procedures; pre-identified communication and incident command systems; effective leadership; and weak financial structures are the main hindering factors in mounting an adequate response to the floods. Conclusion The 2008 flood challenged the primary curative and preventive health care services in Jagatsinghpur. Simple steps like developing facility specific preparedness plans which detail out standard operating procedures during floods and identify clear lines of command will go a long way in strengthening the response to future floods. Performance critiques provided by the grass roots workers, like this one, should be used for institutional learning and effective preparedness planning. Additionally each

  13. The Discovery Channel Telescope

    NASA Astrophysics Data System (ADS)

    Millis, R. L.; Dunham, E. W.; Sebring, T. A.

    2003-12-01

    Lowell Observatory has joined forces with Discovery Communications, Inc. of Silver Spring, MD to build a 4-meter telescope in Northern Arizona. The proposed site is at 7760 ft. altitude at the edge of the Mogollon Rim approximately 40 miles south of Flagstaff, AZ. Intensive DIMM measurements at this site over the past two-and-a-half years have consistently shown median image quality near 0.8 arcsec FWHM. The telescope will have two modes of operation. In survey mode, a prime focus mosaic CCD camera will cover a two-degree-diameter field-of-view. UV/optical spectroscopy, infrared imaging and spectroscopy, and other applications will be supported at the alternate f/6.5 Ritchey-Chretien focus. The ULE primary and secondary mirror blanks are being manufactured by Corning. Goodrich Aerospace is doing the detailed optical design, Vertex RSI is responsible for the design of the telescope's mechanical structure, and M3 is designing the enclosure. Ground-breaking is scheduled for mid-2004 with first light in December 2007. Institutions interested in the possibility of joining this project should contact one of the authors.

  14. Stemina biomarker discovery.

    PubMed

    Cezar, Gabriela G; Donley, Elizabeth L R

    2008-09-01

    Stemina Biomarker Discovery was established in 2006 to commercialize technology developed by Dr Gabriela Cezar at the University of Wisconsin (WI, USA). Stemina's cell-based assays arise from the strategic convergence of two cutting edge technologies: metabolomics and human embryonic stem (hES) cells. Stemina analyzes the small molecules secreted by hES cells and differentiated cell types such as neural and heart cells derived from hES cells by liquid chromatography mass spectrometry at its state-of-the-art facilities in Madison, WI, USA. Stemina's first technology platform has identified a dynamic set of small molecules in the extracellular secretome of hES cells secreted in response to exposure to a library of known teratogens. Alterations to small molecules in the biochemical pathway(s) of hES cells are mapped in silico to identify biomarkers of toxicity for drug screening and development in an all human system. These small human molecules may then be translated in vivo as biomarkers of toxic response and disease.

  15. Discovery and Formulation

    NASA Astrophysics Data System (ADS)

    Clark, Don; Rodger, Caroline

    The uses of Raman spectroscopy in active pharmaceutical ingredient (API) discovery, development and release cover a wide variety of sample types and applications. However, the technique does not have a high prominence in the pharmaceutical industry despite being recognised by regulatory authorities as a suitable methodology for the analysis and release of pharmaceutical API and products. One reason is that other analytical techniques are well established and changing to Raman methods is cost prohibitive considering return on investments (ROI). In addition the technique is often regarded as being one for "experts" and not one for main stream applications. As a consequence Raman spectroscopy is frequently the 2nd or 3rd technique of choice for a specific application. However, due to its unique sampling attributes (e.g. micro and macro measurements direct from the sample, through glass, from well plates or in the presence of water) and selectivity, applications of this technology are found throughout the life cycles of pharmaceutical products. It can therefore be considered to be a spectroscopic common denominator. This chapter highlights a number of routine, specialised and niche Raman spectroscopy applications which have been used in the development of new medicines while detailing some of the limitations of these approaches.

  16. Discoveries in peripartum cardiomyopathy.

    PubMed

    Fett, James D; Markham, David W

    2015-07-01

    The past decade has seen remarkable gains for outcomes in peripartum cardiomyopathy (PPCM), one of the leading causes of maternal mortality and morbidity in the USA and many other countries, including the high-incidence areas of Haiti and South Africa. This review article emphasizes the importance of continuing the process of increasing awareness of PPCM and presents details of this evolving picture, including important discoveries that point the way to full recovery for almost all PPCM subjects. In addition, new interventions will be highlighted, which may facilitate recovery. Numerous studies have demonstrated that when the diagnosis of PPCM is made with LVEF > 0.30, the probability is that recovery to LVEF ≥ 0.50 will occur in the overwhelming majority of subjects. PPCM patients diagnosed with severely depressed systolic function (LVEF < 0.30) and a remodeled left ventricle with greater dilatation (LVEDd ≥ 60mm) are least likely to reach the outcome recovery goals. These are the patients with the greatest need for newer interventional strategies.

  17. A double discovery

    NASA Image and Video Library

    2017-09-27

    The galaxy, NGC 178 may be small, but it packs quite a punch. Measuring around 40,000 light-years across, its diameter is less than half that of the Milky Way, and it is accordingly classified as a dwarf galaxy. Despite its diminutive size, NGC 178 is busy forming new stars. On average, the galaxy forms stars totaling around half the mass of the Sun per year — enough to label it a starburst galaxy. The galaxy’s discovery is an interesting, and somewhat confusing, story. It was originally discovered by American astronomer Ormond Stone in 1885 and dubbed NGC 178, but its position in the sky was recorded incorrectly — by accident the value for the galaxy’s right ascension (which can be thought of as the celestial equivalent of terrestrial longitude) was off by a considerable amount. In the years that followed NGC 178 was spotted again, this time by French astronomer Stéphane Javelle. As no cataloged object occupied that position in the sky, Javelle believed he had discovered a new galaxy and entered it into the expanded Index Catalog under the name IC 39. Later, American astronomer Herbert Howe also observed the object and corrected Stone’s initial mistake. Many years later, astronomers finally noticed that NGC 178 and IC 39 were actually the same object! This image of NGC 178 comprises data gathered by the Wide Field Planetary Camera 2 aboard the NASA/ESA Hubble Space Telescope. Credit: ESA/Hubble & NASA

  18. Novel Directions for Diabetes Mellitus Drug Discovery

    PubMed Central

    Maiese, Kenneth; Chong, Zhao Zhong; Shang, Yan Chen; Wang, Shaohui

    2012-01-01

    Introduction Diabetes mellitus impacts almost 200 million individuals worldwide and leads to debilitating complications. New avenues of drug discovery must target the underlying cellular processes of oxidative stress, apoptosis, autophagy, and inflammation that can mediate multi-system pathology during diabetes mellitus. Areas Covered We examine novel directions for drug discovery that involve the β-nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide, the cytokine erythropoietin, the NAD+-dependent protein histone deacetylase SIRT1, the serine/threonine-protein kinase mammalian target of rapamycin (mTOR), and the wingless pathway. Implications for the targeting of these pathways that oversee gluconeogenic genes, insulin signaling and resistance, fatty acid beta-oxidation, inflammation, and cellular survival are presented. Expert Opinion Nicotinamide, erythropoietin, and the downstram pathways of SIRT1, mTOR, forkhead transcription factors, and wingless signaling offer exciting prospects for novel directions of drug discovery for the treatment of metabolic disorders. Future investigations must dissect the complex relationship and fine modulation of these pathways for the successful translation of robust reparative and regenerative strategies against diabetes mellitus and the complications of this disorder. PMID:23092114

  19. Workshop on Discovery Lessons-Learned

    NASA Technical Reports Server (NTRS)

    Saunders, M. (Editor)

    1995-01-01

    As part of the Discovery Program's continuous improvement effort, a Discovery Program Lessons-Learned workshop was designed to review how well the Discovery Program is moving toward its goal of providing low-cost research opportunities to the planetary science community while ensuring continued U.S. leadership in solar system exploration. The principal focus of the workshop was on the recently completed Announcement of Opportunity (AO) cycle, but the program direction and program management were also open to comment. The objective of the workshop was to identify both the strengths and weaknesses of the process up to this point, with the goal of improving the process for the next AO cycle. The process for initializing the workshop was to solicit comments from the communities involved in the program and to use the feedback as the basis for establishing the workshop agenda. The following four sessions were developed after reviewing and synthesizing both the formal feedback received and informal feedback obtained during discussions with various participants: (1) Science and Return on Investment; (2) Technology vs. Risk; Mission Success and Other Factors; (3) Cost; and (4) AO.AO Process Changes and Program Management.

  20. Bringing together the academic drug discovery community

    PubMed Central

    Slusher, Barbara S.; Conn, P. Jeffrey; Frye, Stephen; Glicksman, Marcie; Arkin, Michelle

    2014-01-01

    The newly formed Academic Drug Discovery Consortium (ADDC) aims to support the growing numbers of university centres engaged in drug discovery that have emerged in response to recent changes in the drug discovery ecosystem. PMID:24172316

  1. External Tank after Separation from Discovery

    NASA Image and Video Library

    2010-04-07

    S131-E-005919 (5 April 2010) --- Space shuttle Discovery?s external fuel tank (ET) is featured in this image photographed by the umbilical well camera aboard Discovery shortly after separating from the shuttle following launch.

  2. External Tank after Separation from Discovery

    NASA Image and Video Library

    2010-04-07

    S131-E-005928 (5 April 2010) --- Space shuttle Discovery?s external fuel tank (ET) is featured in this image photographed by the umbilical well camera aboard Discovery shortly after separating from the shuttle following launch.

  3. 37 CFR 41.150 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... COMMERCE PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Contested Cases § 41.150 Discovery. (a) Limited... to discovery among themselves at any time. (b) Automatic discovery. (1) Within 21 days of a request...

  4. STS-114: Discovery Post MMT Press Conference

    NASA Technical Reports Server (NTRS)

    2005-01-01

    Bruce Buckingham from NASA Public Affairs introduces the panel who consists of: Wayne Hale, Space Shuttle Program Deputy Manager; John Muratore, Manager, Space Shuttle Systems and Integration; and Mike Wetmore, Director of Shuttle Processing. Hale begins with a video presentation of the point sensor box (black box) and discusses the troubleshooting plans that are in place to fix the low level fuel sensor inside the External Tank of the Space Shuttle Discovery. Muratore talks about exploring conditions that may be causing the problem and Wetmore discusses completing scrub securing. Questions from the news media pertaining to solutions to the sensor problem, risks involved, and anomalies are addressed.

  5. Deep Learning in Drug Discovery.

    PubMed

    Gawehn, Erik; Hiss, Jan A; Schneider, Gisbert

    2016-01-01

    Artificial neural networks had their first heyday in molecular informatics and drug discovery approximately two decades ago. Currently, we are witnessing renewed interest in adapting advanced neural network architectures for pharmaceutical research by borrowing from the field of "deep learning". Compared with some of the other life sciences, their application in drug discovery is still limited. Here, we provide an overview of this emerging field of molecular informatics, present the basic concepts of prominent deep learning methods and offer motivation to explore these techniques for their usefulness in computer-assisted drug discovery and design. We specifically emphasize deep neural networks, restricted Boltzmann machine networks and convolutional networks.

  6. Shuttle Discovery Fly-Over

    NASA Image and Video Library

    2012-04-17

    Space shuttle Discovery, mounted atop a NASA 747 Shuttle Carrier Aircraft (SCA) flies over the Steven F. Udvar-Hazy Center, Tuesday, April 17, 2012, in Washington. Discovery, the first orbiter retired from NASA’s shuttle fleet, completed 39 missions, spent 365 days in space, orbited the Earth 5,830 times, and traveled 148,221,675 miles. NASA will transfer Discovery to the National Air and Space Museum to begin its new mission to commemorate past achievements in space and to educate and inspire future generations of explorers. Photo Credit: (NASA/Smithsonian Institution/Dane Penland)

  7. Discovery of natural resources

    USGS Publications Warehouse

    Guild, P.W.

    1976-01-01

    Mankind will continue to need ores of more or less the types and grades used today to supply its needs for new mineral raw materials, at least until fusion or some other relatively cheap, inexhaustible energy source is developed. Most deposits being mined today were exposed at the surface or found by relatively simple geophysical or other prospecting techniques, but many of these will be depleted in the foreseeable future. The discovery of deeper or less obvious deposits to replace them will require the conjunction of science and technology to deduce the laws that governed the concentration of elements into ores and to detect and evaluate the evidence of their whereabouts. Great theoretical advances are being made to explain the origins of ore deposits and understand the general reasons for their localization. These advances have unquestionable value for exploration. Even a large deposit is, however, very small, and, with few exceptions, it was formed under conditions that have long since ceased to exist. The explorationist must suppress a great deal of "noise" to read and interpret correctly the "signals" that can define targets and guide the drilling required to find it. Is enough being done to ensure the long-term availability of mineral raw materials? The answer is probably no, in view of the expanding consumption and the difficulty of finding new deposits, but ingenuity, persistence, and continued development of new methods and tools to add to those already at hand should put off the day of "doing without" for many years. The possibility of resource exhaustion, especially in view of the long and increasing lead time needed to carry out basic field and laboratory studies in geology, geophysics, and geochemistry and to synthesize and analyze the information gained from them counsels against any letting down of our guard, however (17). Research and exploration by government, academia, and industry must be supported and encouraged; we cannot wait until an eleventh

  8. Drug discovery: lessons from evolution

    PubMed Central

    Warren, John

    2011-01-01

    A common view within the pharmaceutical industry is that there is a problem with drug discovery and we should do something about it. There is much sympathy for this from academics, regulators and politicians. In this article I propose that lessons learnt from evolution help identify those factors that favour successful drug discovery. This personal view is influenced by a decade spent reviewing drug development programmes submitted for European regulatory approval. During the prolonged gestation of a new medicine few candidate molecules survive. This process of elimination of many variants and the survival of so few has much in common with evolution, an analogy that encourages discussion of the forces that favour, and those that hinder, successful drug discovery. Imagining a world without vaccines, anaesthetics, contraception and anti-infectives reveals how medicines revolutionized humanity. How to manipulate conditions that favour such discoveries is worth consideration. PMID:21395642

  9. Knowledge discovery in astronomical data

    NASA Astrophysics Data System (ADS)

    Zhang, Yanxia; Zheng, Hongwen; Zhao, Yongheng

    2008-08-01

    With the construction and development of ground-based and space-based observatories, astronomical data amount to Terascale, even Petascale. How to extract knowledge from so huge data volume by automated methods is a big challenge for astronomers. Under this situation, many researchers have studied various approaches and developed different softwares to solve this issue. According to the special task of data mining, we need to select an appropriate technique suiting the requirement of data characteristics. Moreover all algorithms have their own pros and cons. We introduce the characteristics of astronomical data, present the taxonomy of knowledge discovery, and describe the functionalities of knowledge discovery in detail. Then the methods of knowledge discovery are touched upon. Finally the successful applications of data mining techniques in astronomy are summarized and reviewed. Facing data avalanche in astronomy, knowledge discovery in databases (KDD) shows its superiority.

  10. Discovery of the krypton isotopes

    SciTech Connect

    Heim, M.; Fritsch, A.; Schuh, A.; Shore, A.; Thoennessen, M.

    2010-07-15

    Thirty-two krypton isotopes have been observed so far and the discovery of these isotopes is discussed here. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  11. RAS - Screens & Assays - Drug Discovery

    Cancer.gov

    The RAS Drug Discovery group aims to develop assays that will reveal aspects of RAS biology upon which cancer cells depend. Successful assay formats are made available for high-throughput screening programs to yield potentially effective drug compounds.

  12. Discovery – Development of Rituximab

    Cancer.gov

    NCI funded the development of rituximab, one of the first monoclonal antibody cancer treatments. With the discovery of rituximab, more than 70 percent of patients diagnosed with non-hodgkin lymphoma now live five years past their initial diagnosis.

  13. Synthetic biology of antimicrobial discovery

    PubMed Central

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  14. Drug discovery: lessons from evolution.

    PubMed

    Warren, John

    2011-04-01

    A common view within the pharmaceutical industry is that there is a problem with drug discovery and we should do something about it. There is much sympathy for this from academics, regulators and politicians. In this article I propose that lessons learnt from evolution help identify those factors that favour successful drug discovery. This personal view is influenced by a decade spent reviewing drug development programmes submitted for European regulatory approval. During the prolonged gestation of a new medicine few candidate molecules survive. This process of elimination of many variants and the survival of so few has much in common with evolution, an analogy that encourages discussion of the forces that favour, and those that hinder, successful drug discovery. Imagining a world without vaccines, anaesthetics, contraception and anti-infectives reveals how medicines revolutionized humanity. How to manipulate conditions that favour such discoveries is worth consideration. © 2011 The Author. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  15. Serendipity: Accidental Discoveries in Science

    NASA Astrophysics Data System (ADS)

    Roberts, Royston M.

    1989-06-01

    Many of the things discovered by accident are important in our everyday lives: Teflon, Velcro, nylon, x-rays, penicillin, safety glass, sugar substitutes, and polyethylene and other plastics. And we owe a debt to accident for some of our deepest scientific knowledge, including Newton's theory of gravitation, the Big Bang theory of Creation, and the discovery of DNA. Even the Rosetta Stone, the Dead Sea Scrolls, and the ruins of Pompeii came to light through chance. This book tells the fascinating stories of these and other discoveries and reveals how the inquisitive human mind turns accident into discovery. Written for the layman, yet scientifically accurate, this illuminating collection of anecdotes portrays invention and discovery as quintessentially human acts, due in part to curiosity, perserverance, and luck.

  16. Arnold on Discovery Middeck (MDDK)

    NASA Image and Video Library

    2009-03-16

    S119-E-005004 (15 March 2009) --- Astronaut Richard Arnold, STS-119 mission specialist, attired in his shuttle launch and entry suit, gives a “thumbs-up” signal on the middeck of Space Shuttle Discovery during postlaunch activities.

  17. Discovery Performs Terminal Initiation Burn

    NASA Image and Video Library

    The terminal initiation burn, a left Orbital Maneuvering System engine firing that gave Discovery one last big push toward the space station, took place Feb. 26, 2011 at 10:33 a.m. The burn lasted ...

  18. Students Excited by Stellar Discovery

    NASA Astrophysics Data System (ADS)

    2011-02-01

    companion that exploded in a supernova, disrupting its orbit," McLaughlin said. Astronomers and students will work together in the coming months to find answers to these questions. The PSC is a joint project of the National Radio Astronomy Observatory and West Virginia University, funded by a grant from the National Science Foundation. The PSC, led by NRAO Education Officer Sue Ann Heatherly and Project Director Rachel Rosen, includes training for teachers and student leaders, and provides parcels of data from the GBT to student teams. The project involves teachers and students in helping astronomers analyze data from the GBT, a giant, 17-million-pound telescope. Some 300 hours of observing data were reserved for analysis by student teams. Thompson, Snider, and Mabry have been working with about 170 other students across the country. The responsibility for the work, and for the discoveries, is theirs. They are trained by astronomers and by their teachers to distinguish between pulsars and noise. The students' collective judgment sifts the pulsars from the noise. All three students had analyzed thousands of data plots before coming upon this one. Casey Thompson, who has been with the PSC for three years, has analyzed more than 30,000 plots. "Sometimes I just stop and think about the fact that I'm looking at data from space," Thompson said. "It's really special to me." In addition to this discovery, two other astronomical objects have been discovered by students. In 2009, Shay Bloxton of Summersville, WV, discovered a pulsar that spins once every four seconds, and Lucas Bolyard of Clarksburg, WV, discovered a rapidly rotating radio transient, which astronomers believe is a pulsar that emits radio waves in bursts. Those involved in the PSC hope that being a part of astronomy will give students an appreciation for science. Maybe the project will even produce some of the next generation of astronomers. Snider, surely, has been inspired. "The PSC changed my career path

  19. Resilience of aging populations after devastating earthquake event and its determinants - A case study of the Chi-Chi earthquake in Taiwan

    NASA Astrophysics Data System (ADS)

    Hung, Chih-Hsuan; Hung, Hung-Chih

    2016-04-01

    1.Background Major portions of urban areas in Asia are highly exposed and vulnerable to devastating earthquakes. Many studies identify ways to reduce earthquake risk by concentrating more on building resilience for the particularly vulnerable populations. By 2020, as the United Nations' warning, many Asian countries would become 'super-aged societies', such as Taiwan. However, local authorities rarely use resilience approach to frame earthquake disaster risk management and land use strategies. The empirically-based research about the resilience of aging populations has also received relatively little attention. Thus, a challenge arisen for decision-makers is how to enhance resilience of aging populations within the context of risk reduction. This study aims to improve the understanding of the resilience of aging populations and its changes over time in the aftermath of a destructive earthquake at the local level. A novel methodology is proposed to assess the resilience of aging populations and to characterize their changes of spatial distribution patterns, as well as to examine their determinants. 2.Methods and data An indicator-based assessment framework is constructed with the goal of identifying composite indicators (including before, during and after a disaster) that could serve as proxies for attributes of the resilience of aging populations. Using the recovery process of the Chi-Chi earthquake struck central Taiwan in 1999 as a case study, we applied a method combined a geographical information system (GIS)-based spatial statistics technique and cluster analysis to test the extent of which the resilience of aging populations is spatially autocorrelated throughout the central Taiwan, and to explain why clustering of resilient areas occurs in specific locations. Furthermore, to scrutinize the affecting factors of resilience, we develop an aging population resilience model (APRM) based on existing resilience theory. Using the APRM, we applied a multivariate

  20. Launch of STS-63 Discovery

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This wide lux image of the Space Shuttle Discovery as it began its race to catch up with Russia's Mir Space Station shows the base of the launch pad as well as the orbiter just clearing the gantry. Liftoff from Launch Pad 39B, Kennedy Space Center (KSC) occurred at 12:22:04 (EST) February 3, 1995. Discovery is the first in the current fleet of four space shuttle vehicles to make 20 launches.

  1. Launch of STS-63 Discovery

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A 35mm camera was used to expose this close-up image of the Space Shuttle Discovery as it began its race to catch up with Russia's Mir Space Station. Liftoff from Launch Pad 39B, Kennedy Space Center (KSC) occurred at 12:22:04 (EST) February 3, 1995. Discovery is the first in the current fleet of four space shuttle vehicles to make 20 launches.

  2. Launch of STS-63 Discovery

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This wide lux image of the Space Shuttle Discovery as it began its race to catch up with Russia's Mir Space Station shows the base of the launch pad as well as the orbiter just clearing the gantry. Liftoff from Launch Pad 39B, Kennedy Space Center (KSC) occurred at 12:22:04 (EST) February 3, 1995. Discovery is the first in the current fleet of four space shuttle vehicles to make 20 launches.

  3. Launch of STS-63 Discovery

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A 35mm camera was used to expose this image of the Space Shuttle Discovery as it began its race to catch up with Russia's Mir Space Station. Liftoff from Launch Pad 39B, Kennedy Space Center (KSC) occurred at 12:22:04 (EST) February 3, 1995. Discovery is the first in the current fleet of four space shuttle vehicles to make 20 launches. The launch pad and orbiter can be seen reflected in the water directly in front of it.

  4. Launch of STS-63 Discovery

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A 70mm camera was used to expose this image of the Space Shuttle Discovery as it began its race to catch up with Russia's Mir Space Station. Liftoff from Launch Pad 39B, Kennedy Space Center (KSC) occurred at 12:22:04 (EST) February 3, 1995. Discovery is the first in the current fleet of four space shuttle vehicles to make 20 launches. The launch pad and orbiter can be seen reflected in the water directly in front of it.

  5. Metagenomic small molecule discovery methods

    PubMed Central

    Charlop-Powers, Zachary; Milshteyn, Aleksandr; Brady, Sean F.

    2014-01-01

    Metagenomic approaches to natural product discovery provide the means of harvesting bioactive small molecules synthesized by environmental bacteria without the requirement of first culturing these organisms. Advances in sequencing technologies and general metagenomic methods are beginning to provide the tools necessary to unlock the unexplored biosynthetic potential encoded by the genomes of uncultured environmental bacteria. Here, we highlight recent advances in sequence- and functional- based metagenomic approaches that promise to facilitate antibiotic discovery from diverse environmental microbiomes. PMID:25000402

  6. Discovery STS-133 Mission Landing

    NASA Image and Video Library

    2011-03-09

    NASA Administrator Charles Bolden, right, and NASA Executive Officer to the Deputy Administrator Garvey McIntosh scan the sky for the space shuttle Discovery as it approaches for landing from its 39th and final flight at the Kennedy Space Center in Cape Canaveral, Fla., Wednesday, March 9, 2011. Since 1984, Discovery flew 39 missions, spent 365 days in space, orbited Earth 5,830 times and traveled 148,221,675 miles. Photo credit: (NASA/Bill Ingalls)

  7. Discovery STS-133 Mission Landing

    NASA Image and Video Library

    2011-03-09

    The runway of the Shuttle Landing Facility (SLF) is marked to show where the wheels stopped for the space shuttle Discovery (STS-133) shortly after it landed, Wednesday, March 9, 2011, at Kennedy Space Center in Cape Canaveral, Fla., completing its 39th and final flight. Since 1984, Discovery flew 39 missions, spent 365 days in space, orbited Earth 5,830 times and traveled 148,221,675 miles. Photo credit: (NASA/Bill Ingalls)

  8. Computational methods in drug discovery

    PubMed Central

    Leelananda, Sumudu P

    2016-01-01

    The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed. PMID:28144341

  9. Computational methods in drug discovery.

    PubMed

    Leelananda, Sumudu P; Lindert, Steffen

    2016-01-01

    The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein-ligand docking, pharmacophore modeling and QSAR techniques are reviewed.

  10. Discovery of the Wavemaker

    NASA Image and Video Library

    2005-05-10

    Cassini's celestial sleuthing has paid off with this time-lapse series of images which confirmed earlier suspicions that a small moon was orbiting within the narrow Keeler gap of Saturn's rings. The movie sequence, which consists of 12 images taken over 16 minutes while Cassini gazed down upon the sunlit side of the A ring, shows a tiny moon orbiting in the center of the Keeler gap, churning up waves in the gap edges as it goes. The pattern of waves travels with the moon in its orbit. The Keeler gap is located about 250 kilometers (155 miles) inside the outer edge of the A ring, which is also the outer edge of the bright main rings. The new object is about 7 kilometers across (4 miles) and reflects about 50 percent of the sunlight that falls upon it -- a brightness that is typical of particles in the nearby rings. The new body has been provisionally named S/2005 S1. Imaging scientists predicted the moon's presence and its orbital distance from Saturn after July 2004, when they saw a set of peculiar spiky and wispy features in the Keeler gap's outer edge. The similarities of the Keeler gap features to those noted in Saturn's F ring and the Encke gap led the scientists to conclude that a small body, a few kilometers across, was lurking in the center of the Keeler gap, awaiting discovery. Also included here is a view of the same scene created by combining six individual, unmagnified frames used in the movie sequence. This digital composite view improves the overall resolution of the scene compared to that available in any of the single images. The images in this movie sequence were obtained with the Cassini spacecraft narrow-angle camera on May 1, 2005, at a distance of approximately 1.1 million kilometers (708,000 miles) from Saturn. Resolution in the original image was 8 kilometers (5 miles) per pixel. The images in the movie sequence have been magnified in (the vertical direction only) by a factor of two to aid visibility of features caused within the gap by the

  11. Biomarkers for kidney involvement in pediatric lupus

    PubMed Central

    Goilav, Beatrice; Putterman, Chaim; Rubinstein, Tamar B

    2015-01-01

    Lupus nephritis (LN), the renal involvement in systemic lupus erythematosus, is currently diagnosed by histopathology obtained by percutaneous renal biopsy and is associated with increased morbidity and mortality in both adults and children. LN is more prevalent and severe in children, requiring aggressive and prolonged immunosuppression. The consequences of the diagnosis and its treatment have devastating long-term effects on the growth, well-being and quality of life of affected children. The paucity of reliable clinical indicators of the presence and severity of renal involvement have contributed to a halt in the reduction of progression to end-stage renal disease in recent years. Here, we discuss the recent development of biomarkers in the management of LN and their role as therapeutic targets. PMID:26079958

  12. Knowledge discovery process for scientific and engineering data

    NASA Astrophysics Data System (ADS)

    Barrios, Luis J.; Rudolph, Stephan

    2002-03-01

    Scientists and engineers are often confronted with the problem of modeling the physical laws that govern complex processes and systems. This task may generally be accomplished following traditional modeling procedures. However, when dealing with multivariate problems and/or huge quantities of experimental data, the modeling problem can easily become unmanageable. In such cases, knowledge discovery techniques may help to address this problem. Current knowledge discovery methods however rely mainly on inductive data mining techniques and do not make use of the structural properties of the specific physical context. Hence, they are not yet the ideal process solution for discovering functional models in science and engineering. This paper discusses a knowledge discovery process, which combines deductive and inductive reasoning techniques to find out mathematical models of physical systems. In the supplementary deductive process, the technique of dimensional analysis is used. This allows the incorporation of background knowledge of the involved domain to enrich the general process of knowledge discovery. The background knowledge forms hereby the specific context for a knowledge discovery process for concrete scientific data. As an example, the introduced method is used to find out the expression of the drag force that a viscous fluid exerts on a submersed and uniformly moving solid. The various issues that arise in the development and implementation of such a knowledge discovery system based on the method of dimensional analysis are analyzed and discussed.

  13. Historical Review of Californium-252 Discovery and Development

    DOE R&D Accomplishments Database

    Stoddard, D. H.

    1985-01-01

    This paper discusses the discovery and history of californium 252. This isotope may be synthesized by irradiating plutonium 239, plutonium 242, americium 243, or curium 244 with neutrons in a nuclear reactor. Various experiments and inventions involving Cf conducted at the Savannah River Plant are discussed. The evolution of radiotherapy using californium 252 is reviewed. (PLG)

  14. 28 CFR 68.18 - Discovery-general provisions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... FOR ADMINISTRATIVE HEARINGS BEFORE ADMINISTRATIVE LAW JUDGES IN CASES INVOLVING ALLEGATIONS OF... be limited by the Administrative Law Judge upon his or her own initiative or pursuant to a motion... Administrative Law Judge in accordance with the rules in this part, the parties may obtain discovery regarding...

  15. A Safer, Discovery-Based Nucleophilic Substitution Experiment

    ERIC Educational Resources Information Center

    Horowitz, Gail

    2009-01-01

    A discovery-based nucleophilic substitution experiment is described in which students compare the reactivity of chloride and iodide ions in an S[subscript N]2 reaction. This experiment improves upon the well-known "Competing Nucleophiles" experiment in that it does not involve the generation of hydrogen halide gas. The experiment also introduces…

  16. A Safer, Discovery-Based Nucleophilic Substitution Experiment

    ERIC Educational Resources Information Center

    Horowitz, Gail

    2009-01-01

    A discovery-based nucleophilic substitution experiment is described in which students compare the reactivity of chloride and iodide ions in an S[subscript N]2 reaction. This experiment improves upon the well-known "Competing Nucleophiles" experiment in that it does not involve the generation of hydrogen halide gas. The experiment also introduces…

  17. Discovery and Nurturance of Giftedness in the Culturally Different.

    ERIC Educational Resources Information Center

    Torrance, E. Paul

    Discussed in the monograph are methods for identifying and developing programs for culturally different gifted students. In an overview section, the important issues and trends associated with the discovery and nurturance of giftedness among the culturally different are considered; and screening methods which involve modified traditional…

  18. Historical review of californium-252 discovery and development

    SciTech Connect

    Stoddard, D.H.

    1985-01-01

    This paper discusses the discovery and history of californium 252. This isotope may be synthesized by irradiating plutonium 239, plutonium 242, americium 243, or curium 244 with neutrons in a nuclear reactor. Various experiments and inventions involving /sup 252/Cf conducted at the Savannah River Plant are discussed. The evolution of radiotherapy using californium 252 is reviewed. (PLG)

  19. Historical review of californium-252 discovery and development

    NASA Astrophysics Data System (ADS)

    Stoddard, D. H.

    This paper discusses the discovery and history of californium 252. This isotope may be synthesized by irradiating plutonium 239, plutonium 242, americium 243, or curium 244 with neutrons in a nuclear reactor. Various experiments and inventions involving (252)Cf conducted at the Savannah River Plant are discussed. The evolution of radiotherapy using californium 252 is reviewed.

  20. Sciencing and Discovery: Arizona HSST/CDA Competency Based Training Module #16.

    ERIC Educational Resources Information Center

    Workman, Stefanie; Pintchovski, Susan

    This Child Development Associate (CDA) training module helps interns develop children's science exploration and discovery skills. This process of discovering is known as sciencing. Teachers can create the climate for discovery by becoming actively involved with the children, by sharing the children's natural curiosity about their environment, and…

  1. Discovery in Motion: Movement Exploration for Problem-Solving and Self-Concept.

    ERIC Educational Resources Information Center

    Gilroy, Pamela J.

    The movement-exploration activities described in this book are designed to appeal to primary-level children's natural instinct toward imaginative play and discovery and offer opportunities to develop physical skills in a familiar environment. The discovery of the physical self involves body-part and body-surface identification, isolated movements…

  2. RESEARCH CONFERENCE ON "LEARNING BY DISCOVERY" (NEW YORK CITY, JANUARY 28-29, 1965).

    ERIC Educational Resources Information Center

    CRONBACH, LEE J.

    A TWO DAY RESEARCH CONFERENCE ON "LEARNING BY DISCOVERY" WAS HELD TO--(1) CLARIFY SOME OF THE ISSUES INVOLVED IN LEARNING BY DISCOVERY, (2) REVIEW WHAT IS KNOWN OF THE SUBJECT, AND (3) SUGGEST WAYS OF EXTENDING KNOWLEDGE ABOUT IT. THE 25 PARTICIPANTS WERE REPRESENTATIVES FROM MANY AREAS IN PSYCHOLOGY AND EDUCATION. OBSERVERS FROM GOVERNMENT…

  3. Discovery in Motion: Movement Exploration for Problem-Solving and Self-Concept.

    ERIC Educational Resources Information Center

    Gilroy, Pamela J.

    The movement-exploration activities described in this book are designed to appeal to primary-level children's natural instinct toward imaginative play and discovery and offer opportunities to develop physical skills in a familiar environment. The discovery of the physical self involves body-part and body-surface identification, isolated movements…

  4. Establishing an In Vivo Assay System to Identify Components Involved in Environmental RNA Interference in the Western Corn Rootworm

    PubMed Central

    Miyata, Keita; Ramaseshadri, Parthasarathy; Zhang, Yuanji; Segers, Gerrit; Bolognesi, Renata; Tomoyasu, Yoshinori

    2014-01-01

    The discovery of environmental RNA interference (RNAi), in which gene expression is suppressed via feeding with double-stranded RNA (dsRNA) molecules, opened the door to the practical application of RNAi-based techniques in crop pest management. The western corn rootworm (WCR, Diabrotica virgifera virgifera) is one of the most devastating corn pests in North America. Interestingly, WCR displays a robust environmental RNAi response, raising the possibility of applying an RNAi-based pest management strategy to this pest. Understanding the molecular mechanisms involved in the WCR environmental RNAi process will allow for determining the rate limiting steps involved with dsRNA toxicity and potential dsRNA resistance mechanisms in WCR. In this study, we have established a two-step in vivo assay system, which allows us to evaluate the involvement of genes in environmental RNAi in WCR. We show that laccase 2 and ebony, critical cuticle pigmentation/tanning genes, can be used as marker genes in our assay system, with ebony being a more stable marker to monitor RNAi activity. In addition, we optimized the dsRNA dose and length for the assay, and confirmed that this assay system is sensitive to detect well-known RNAi components such as Dicer-2 and Argonaute-2. We also evaluated two WCR sid1- like (sil) genes with this assay system. This system will be useful to quickly survey candidate systemic RNAi genes in WCR, and also will be adaptable for a genome-wide RNAi screening to give us an unbiased view of the environmental/systemic RNAi pathway in WCR. PMID:25003334

  5. Establishing an in vivo assay system to identify components involved in environmental RNA interference in the western corn rootworm.

    PubMed

    Miyata, Keita; Ramaseshadri, Parthasarathy; Zhang, Yuanji; Segers, Gerrit; Bolognesi, Renata; Tomoyasu, Yoshinori

    2014-01-01

    The discovery of environmental RNA interference (RNAi), in which gene expression is suppressed via feeding with double-stranded RNA (dsRNA) molecules, opened the door to the practical application of RNAi-based techniques in crop pest management. The western corn rootworm (WCR, Diabrotica virgifera virgifera) is one of the most devastating corn pests in North America. Interestingly, WCR displays a robust environmental RNAi response, raising the possibility of applying an RNAi-based pest management strategy to this pest. Understanding the molecular mechanisms involved in the WCR environmental RNAi process will allow for determining the rate limiting steps involved with dsRNA toxicity and potential dsRNA resistance mechanisms in WCR. In this study, we have established a two-step in vivo assay system, which allows us to evaluate the involvement of genes in environmental RNAi in WCR. We show that laccase 2 and ebony, critical cuticle pigmentation/tanning genes, can be used as marker genes in our assay system, with ebony being a more stable marker to monitor RNAi activity. In addition, we optimized the dsRNA dose and length for the assay, and confirmed that this assay system is sensitive to detect well-known RNAi components such as Dicer-2 and Argonaute-2. We also evaluated two WCR sid1- like (sil) genes with this assay system. This system will be useful to quickly survey candidate systemic RNAi genes in WCR, and also will be adaptable for a genome-wide RNAi screening to give us an unbiased view of the environmental/systemic RNAi pathway in WCR.

  6. 39 CFR 952.21 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... confidential information or documents. (b) Discovery disputes. The parties are required to make a good faith... 39 Postal Service 1 2014-07-01 2014-07-01 false Discovery. 952.21 Section 952.21 Postal Service... AND LOTTERY ORDERS § 952.21 Discovery. (a) Voluntary discovery. The parties are encouraged to...

  7. 39 CFR 955.15 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Discovery. 955.15 Section 955.15 Postal Service... APPEALS § 955.15 Discovery. (a) The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure, the Board may issue any order which...

  8. 39 CFR 952.21 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... confidential information or documents. (b) Discovery disputes. The parties are required to make a good faith... 39 Postal Service 1 2013-07-01 2013-07-01 false Discovery. 952.21 Section 952.21 Postal Service... AND LOTTERY ORDERS § 952.21 Discovery. (a) Voluntary discovery. The parties are encouraged to...

  9. 39 CFR 952.21 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... confidential information or documents. (b) Discovery disputes. The parties are required to make a good faith... 39 Postal Service 1 2012-07-01 2012-07-01 false Discovery. 952.21 Section 952.21 Postal Service... AND LOTTERY ORDERS § 952.21 Discovery. (a) Voluntary discovery. The parties are encouraged to...

  10. 49 CFR 1503.633 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... determines appropriate. (h) Confidential orders. A party or person who has received a discovery request for... 49 Transportation 9 2011-10-01 2011-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery....

  11. 39 CFR 955.15 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Discovery. 955.15 Section 955.15 Postal Service... APPEALS § 955.15 Discovery. (a) The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure, the Board may issue any order which...

  12. 39 CFR 955.15 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Discovery. 955.15 Section 955.15 Postal Service... APPEALS § 955.15 Discovery. (a) The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure, the Board may issue any order which...

  13. 39 CFR 955.15 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Discovery. 955.15 Section 955.15 Postal Service... APPEALS § 955.15 Discovery. (a) The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure, the Board may issue any order which...

  14. 49 CFR 1503.633 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... determines appropriate. (h) Confidential orders. A party or person who has received a discovery request for... 49 Transportation 9 2013-10-01 2013-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery....

  15. 7 CFR 1.322 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... designation of the time or place; (3) That the discovery may be had only through a method of discovery other... 7 Agriculture 1 2010-01-01 2010-01-01 false Discovery. 1.322 Section 1.322 Agriculture Office of... Under the Program Fraud Civil Remedies Act of 1986 § 1.322 Discovery. (a) The following types...

  16. 14 CFR 16.213 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... through other discovery methods permitted under this section; or (4) The method or scope of discovery... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Discovery. 16.213 Section 16.213... PRACTICE FOR FEDERALLY-ASSISTED AIRPORT ENFORCEMENT PROCEEDINGS Hearings § 16.213 Discovery. (a)...

  17. 49 CFR 604.38 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... methods permitted under this section; or (4) The method or scope of discovery requested by the party is... 49 Transportation 7 2010-10-01 2010-10-01 false Discovery. 604.38 Section 604.38 Transportation... TRANSPORTATION CHARTER SERVICE Hearings. § 604.38 Discovery. (a) Permissible forms of discovery shall be...

  18. 28 CFR 76.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Methods. Discovery may be obtained by one or more of the methods provided under the Federal Rules of Civil... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 76.21 Section 76.21 Judicial... POSSESSION OF CERTAIN CONTROLLED SUBSTANCES § 76.21 Discovery. (a) Scope. Discovery under this part...

  19. 43 CFR 4.1130 - Discovery methods.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery methods. 4.1130 Section 4.1130... Special Rules Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by one or more of the following methods— (a) Depositions upon...

  20. Automated Knowledge Discovery From Simulators

    NASA Technical Reports Server (NTRS)

    Burl, Michael; DeCoste, Dennis; Mazzoni, Dominic; Scharenbroich, Lucas; Enke, Brian; Merline, William

    2007-01-01

    A computational method, SimLearn, has been devised to facilitate efficient knowledge discovery from simulators. Simulators are complex computer programs used in science and engineering to model diverse phenomena such as fluid flow, gravitational interactions, coupled mechanical systems, and nuclear, chemical, and biological processes. SimLearn uses active-learning techniques to efficiently address the "landscape characterization problem." In particular, SimLearn tries to determine which regions in "input space" lead to a given output from the simulator, where "input space" refers to an abstraction of all the variables going into the simulator, e.g., initial conditions, parameters, and interaction equations. Landscape characterization can be viewed as an attempt to invert the forward mapping of the simulator and recover the inputs that produce a particular output. Given that a single simulation run can take days or weeks to complete even on a large computing cluster, SimLearn attempts to reduce costs by reducing the number of simulations needed to effect discoveries. Unlike conventional data-mining methods that are applied to static predefined datasets, SimLearn involves an iterative process in which a most informative dataset is constructed dynamically by using the simulator as an oracle. On each iteration, the algorithm models the knowledge it has gained through previous simulation trials and then chooses which simulation trials to run next. Running these trials through the simulator produces new data in the form of input-output pairs. The overall process is embodied in an algorithm that combines support vector machines (SVMs) with active learning. SVMs use learning from examples (the examples are the input-output pairs generated by running the simulator) and a principle called maximum margin to derive predictors that generalize well to new inputs. In SimLearn, the SVM plays the role of modeling the knowledge that has been gained through previous simulation trials

  1. Proteus mirabilis abscess involving the entire neural axis.

    PubMed

    Kamat, A S; Thango, N S; Husein, M Ben

    2016-08-01

    Intramedullary spinal cord abscesses are rare and potentially devastating lesions usually associated with other infective processes such as bacterial endocarditis, or pulmonary or urogenital infection. We describe a 2-year-old girl who presented with an infected dermal sinus leading to an intraspinal abscess. This abscess eventually spread and involved the entire neural axis leaving her quadriparetic. Drainage of the abscess resulted in recovery and the child regained normal function of her limbs. To our knowledge this is the first documented case of an intramedullary abscess involving the entire neural axis.

  2. A Mars Exploration Discovery Program

    NASA Astrophysics Data System (ADS)

    Hansen, C. J.; Paige, D. A.

    2000-07-01

    The Mars Exploration Program should consider following the Discovery Program model. In the Discovery Program a team of scientists led by a PI develop the science goals of their mission, decide what payload achieves the necessary measurements most effectively, and then choose a spacecraft with the capabilities needed to carry the payload to the desired target body. The primary constraints associated with the Discovery missions are time and money. The proposer must convince reviewers that their mission has scientific merit and is feasible. Every Announcement of Opportunity has resulted in a collection of creative ideas that fit within advertised constraints. Following this model, a "Mars Discovery Program" would issue an Announcement of Opportunity for each launch opportunity with schedule constraints dictated by the launch window and fiscal constraints in accord with the program budget. All else would be left to the proposer to choose, based on the science the team wants to accomplish, consistent with the program theme of "Life, Climate and Resources". A proposer could propose a lander, an orbiter, a fleet of SCOUT vehicles or penetrators, an airplane, a balloon mission, a large rover, a small rover, etc. depending on what made the most sense for the science investigation and payload. As in the Discovery program, overall feasibility relative to cost, schedule and technology readiness would be evaluated and be part of the selection process.

  3. The Dynamics of Drug Discovery.

    PubMed

    Moroni, Elisabetta; Paladino, Antonella; Colombo, Giorgio

    2015-01-01

    Proteins are not static objects. To carry out their functions in the cells and participate in biochemical interaction networks, proteins have to explore different conformational substates, which favor the adaptation to different partners and ultimately allow them to respond to changes in the environment. In this paper we discuss the implications of including the atomistic description of protein dynamics and flexibility in the context of drug discovery and design. The underlying idea is that a better understanding of the atomistic details of molecular recognition phenomena and conformational cross-talk between a ligand and a receptor can in fact translate in unexplored opportunities for the discovery of new drug like molecules. We will illustrate and discuss dynamics-based pharmacophores, the discovery of cryptic binding sites, the characterization and exploitation of allosteric regulation mechanisms and the definition of potential protein-protein interaction sites as potential sources of new bases for the rational design of small molecules endowed with specific biological functions. Overall, the inclusion of protein flexibility in the drug discovery process is starting to attract attention not only in the academic but also in the industrial community. This is supported by experimental tests that prove the actual feasibility of considering the explicit dynamics of drug-protein interactions at all relevant levels of resolution and the use of multiple receptor conformations in drug discovery, as affordable complements (if not an alternative) to classical High Throughput Screening (HTS) efforts based on static structures.

  4. The Europa Ocean Discovery mission

    SciTech Connect

    Edwards, B.C.; Chyba, C.F.; Abshire, J.B.

    1997-06-01

    Since it was first proposed that tidal heating of Europa by Jupiter might lead to liquid water oceans below Europa`s ice cover, there has been speculation over the possible exobiological implications of such an ocean. Liquid water is the essential ingredient for life as it is known, and the existence of a second water ocean in the Solar System would be of paramount importance for seeking the origin and existence of life beyond Earth. The authors present here a Discovery-class mission concept (Europa Ocean Discovery) to determine the existence of a liquid water ocean on Europa and to characterize Europa`s surface structure. The technical goal of the Europa Ocean Discovery mission is to study Europa with an orbiting spacecraft. This goal is challenging but entirely feasible within the Discovery envelope. There are four key challenges: entering Europan orbit, generating power, surviving long enough in the radiation environment to return valuable science, and complete the mission within the Discovery program`s launch vehicle and budget constraints. The authors will present here a viable mission that meets these challenges.

  5. A Mars Exploration Discovery Program

    NASA Technical Reports Server (NTRS)

    Hansen, C. J.; Paige, D. A.

    2000-01-01

    The Mars Exploration Program should consider following the Discovery Program model. In the Discovery Program a team of scientists led by a PI develop the science goals of their mission, decide what payload achieves the necessary measurements most effectively, and then choose a spacecraft with the capabilities needed to carry the payload to the desired target body. The primary constraints associated with the Discovery missions are time and money. The proposer must convince reviewers that their mission has scientific merit and is feasible. Every Announcement of Opportunity has resulted in a collection of creative ideas that fit within advertised constraints. Following this model, a "Mars Discovery Program" would issue an Announcement of Opportunity for each launch opportunity with schedule constraints dictated by the launch window and fiscal constraints in accord with the program budget. All else would be left to the proposer to choose, based on the science the team wants to accomplish, consistent with the program theme of "Life, Climate and Resources". A proposer could propose a lander, an orbiter, a fleet of SCOUT vehicles or penetrators, an airplane, a balloon mission, a large rover, a small rover, etc. depending on what made the most sense for the science investigation and payload. As in the Discovery program, overall feasibility relative to cost, schedule and technology readiness would be evaluated and be part of the selection process.

  6. A Passion for Discovery

    ScienceCinema

    Peter Freund

    2016-07-12

    The human side of doing theoretical physics is explored through stories about the interactions between physicists and about the way world events can affect not only the scientists' behavior, but even their scientific interests and style.  These stories cluster nicely around certain bigger themes to create an overarching whole.  This happens both on account of some interesting narrative structures intrinsic to the science of Physics itself and on account of the way Physics integrates into the general culture. The stories concern Einstein, Schrödinger, Pauli, Heisenberg, Stueckelberg, Jordan and Fock and also involve some mathematicians like Emmy Noether, Teichmüller and Bers and even the psychologist C.G. Jung.

  7. The Discovery of the Higgs Boson: America's Role

    SciTech Connect

    2013-10-08

    The discovery of the Higgs boson was an international endeavor, involving thousands of physicists from across the world. While the accelerator at which the experimental work was done is located on Europe, the US supplied more physicists than any other single country. America had a very large role in the discovery of the Higgs particle and continues to have a leading role in the ongoing studies of the boson's properties. This video describes some of the contributions of U.S. universities and laboratories.

  8. The Discovery of the Higgs Boson: America's Role

    ScienceCinema

    None

    2016-07-12

    The discovery of the Higgs boson was an international endeavor, involving thousands of physicists from across the world. While the accelerator at which the experimental work was done is located on Europe, the US supplied more physicists than any other single country. America had a very large role in the discovery of the Higgs particle and continues to have a leading role in the ongoing studies of the boson's properties. This video describes some of the contributions of U.S. universities and laboratories.

  9. Combinatorial chemistry in drug discovery.

    PubMed

    Liu, Ruiwu; Li, Xiaocen; Lam, Kit S

    2017-06-01

    Several combinatorial methods have been developed to create focused or diverse chemical libraries with a wide range of linear or macrocyclic chemical molecules: peptides, non-peptide oligomers, peptidomimetics, small-molecules, and natural product-like organic molecules. Each combinatorial approach has its own unique high-throughput screening and encoding strategy. In this article, we provide a brief overview of combinatorial chemistry in drug discovery with emphasis on recently developed new technologies for design, synthesis, screening and decoding of combinatorial library. Examples of successful application of combinatorial chemistry in hit discovery and lead optimization are given. The limitations and strengths of combinatorial chemistry are also briefly discussed. We are now in a better position to truly leverage the power of combinatorial technologies for the discovery and development of next-generation drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. The discovery of immunoglobulin E.

    PubMed

    Ribatti, Domenico

    2016-03-01

    The discovery of immunoglobulin E (IgE) was a breakthrough in the field of allergy and immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. The first clue to the existence of a substance responsible for hypersensitivity reactions was demonstrated in 1921 by Prausnitz and Kustner, and after four decades it was identified as an immunoglobulin subclass by Ishizakas and co-workers. In 1968, the WHO International Reference Centre for Immunoglobulins announced the presence of a fifth immunoglobulin isotype, IgE.

  11. Discovery STS-131 Mission Landing

    NASA Image and Video Library

    2010-04-20

    NASA Deputy Administrator Lori Garver and STS-131 Commander Alan G. Poindexter walk around under the space shuttle Discovery shortly after Discovery and the STS-131 crew landed at the Kennedy Space Center in Cape Canaveral, Fla., Tuesday, April 20, 2010. STS-131 mission crew, Commander Alan G. Poindexter, Pilot James P. Dutton Jr. and Mission Specialists Dorothy Metcalf-Lindenburger, Rick Mastracchio, Stephanie Wilson, Clayton Anderson and Japanese astronaut Naoko Yamazaki returned from their 14-day journey of more than 6.2 million miles. The STS-131 mission to the International Space Station delivered science racks, new crew sleeping quarters, equipment and supplies. Photo credit: (NASA/Bill Ingalls)

  12. The Discovery of Dark Energy: Historical Reflections

    NASA Astrophysics Data System (ADS)

    Crease, Robert P.

    2009-09-01

    The discovery of dark energy by supernovae-culminating in Riess et al. Astron. J. 116, 1998, 1009, and Perlmutter et al. Astrophys. J. 511 1999 565-is likely to become a classic discovery story in the history of science. It exhibits at lease five features that attract the interest of historians: 1) the role of evolving techniques in making a discovery possible; 2) the existence of ambiguities in the discovery process; 3) the existence of ambiguities in discovery announcements; 4) different forms of competition and cooperation; and 5) the way discoveries can open new chapters in science. The dark-energy discovery provides dramatic examples of such features, even apart from the differing memories and judgments that may exist about the events. This article engages in a thought-experiment: what in this discovery story is likely to attract the interest of a science historian looking back on this discovery a hundred years from now?

  13. Novel opportunities for computational biology and sociology in drug discovery

    PubMed Central

    Yao, Lixia

    2009-01-01

    Drug discovery today is impossible without sophisticated modeling and computation. In this review we touch on previous advances in computational biology and by tracing the steps involved in pharmaceutical development, we explore a range of novel, high value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry ties for scientific and human benefit. Attention to these opportunities could promise punctuated advance, and will complement the well-established computational work on which drug discovery currently relies. PMID:19674801

  14. Novel opportunities for computational biology and sociology in drug discovery.

    PubMed

    Yao, Lixia; Evans, James A; Rzhetsky, Andrey

    2009-09-01

    Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development, explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies.

  15. Novel opportunities for computational biology and sociology in drug discovery.

    PubMed

    Yao, Lixia; Evans, James A; Rzhetsky, Andrey

    2010-04-01

    Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development,explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery.These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use.Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies.

  16. Applications of chemogenomic library screening in drug discovery.

    PubMed

    Jones, Lyn H; Bunnage, Mark E

    2017-01-20

    The allure of phenotypic screening, combined with the industry preference for target-based approaches, has prompted the development of innovative chemical biology technologies that facilitate the identification of new therapeutic targets for accelerated drug discovery. A chemogenomic library is a collection of selective small-molecule pharmacological agents, and a hit from such a set in a phenotypic screen suggests that the annotated target or targets of that pharmacological agent may be involved in perturbing the observable phenotype. In this Review, we describe opportunities for chemogenomic screening to considerably expedite the conversion of phenotypic screening projects into target-based drug discovery approaches. Other applications are explored, including drug repositioning, predictive toxicology and the discovery of novel pharmacological modalities.

  17. Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy.

    PubMed

    Hathout, Yetrib; Brody, Edward; Clemens, Paula R; Cripe, Linda; DeLisle, Robert Kirk; Furlong, Pat; Gordish-Dressman, Heather; Hache, Lauren; Henricson, Erik; Hoffman, Eric P; Kobayashi, Yvonne Monique; Lorts, Angela; Mah, Jean K; McDonald, Craig; Mehler, Bob; Nelson, Sally; Nikrad, Malti; Singer, Britta; Steele, Fintan; Sterling, David; Sweeney, H Lee; Williams, Steve; Gold, Larry

    2015-06-09

    Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy-Cincinnati Children's Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and healthy volunteers at a 1% false-discovery rate, a large number of significant protein changes for such a small study. These biomarkers can be classified by known cellular processes and by age-dependent changes in protein concentration. Our findings demonstrate both the utility of this unbiased biomarker discovery approach and suggest potential new diagnostic and therapeutic avenues for ameliorating the burden of DMD and, we hope, other rare and devastating diseases.

  18. Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy

    PubMed Central

    Hathout, Yetrib; Brody, Edward; Clemens, Paula R.; Cripe, Linda; DeLisle, Robert Kirk; Furlong, Pat; Gordish-Dressman, Heather; Hache, Lauren; Henricson, Erik; Hoffman, Eric P.; Kobayashi, Yvonne Monique; Lorts, Angela; Mah, Jean K.; McDonald, Craig; Mehler, Bob; Nelson, Sally; Nikrad, Malti; Singer, Britta; Steele, Fintan; Sterling, David; Sweeney, H. Lee; Williams, Steve; Gold, Larry

    2015-01-01

    Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy–Cincinnati Children’s Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and healthy volunteers at a 1% false-discovery rate, a large number of significant protein changes for such a small study. These biomarkers can be classified by known cellular processes and by age-dependent changes in protein concentration. Our findings demonstrate both the utility of this unbiased biomarker discovery approach and suggest potential new diagnostic and therapeutic avenues for ameliorating the burden of DMD and, we hope, other rare and devastating diseases. PMID:26039989

  19. Modeling Truth Existence in Truth Discovery.

    PubMed

    Zhi, Shi; Zhao, Bo; Tong, Wenzhu; Gao, Jing; Yu, Dian; Ji, Heng; Han, Jiawei

    2015-08-01

    When integrating information from multiple sources, it is common to encounter conflicting answers to the same question. Truth discovery is to infer the most accurate and complete integrated answers from conflicting sources. In some cases, there exist questions for which the true answers are excluded from the candidate answers provided by all sources. Without any prior knowledge, these questions, named no-truth questions, are difficult to be distinguished from the questions that have true answers, named has-truth questions. In particular, these no-truth questions degrade the precision of the answer integration system. We address such a challenge by introducing source quality, which is made up of three fine-grained measures: silent rate, false spoken rate and true spoken rate. By incorporating these three measures, we propose a probabilistic graphical model, which simultaneously infers truth as well as source quality without any a priori training involving ground truth answers. Moreover, since inferring this graphical model requires parameter tuning of the prior of truth, we propose an initialization scheme based upon a quantity named truth existence score, which synthesizes two indicators, namely, participation rate and consistency rate. Compared with existing methods, our method can effectively filter out no-truth questions, which results in more accurate source quality estimation. Consequently, our method provides more accurate and complete answers to both has-truth and no-truth questions. Experiments on three real-world datasets illustrate the notable advantage of our method over existing state-of-the-art truth discovery methods.

  20. Scientists Like Me: Faces of Discovery

    NASA Astrophysics Data System (ADS)

    Enevoldsen, A. A. G.; Culp, S.; Trinh, A.

    2010-08-01

    During the International Year of Astronomy, Pacific Science Center is hosting a photography exhibit: Scientists Like Me: Faces of Discovery. The exhibit contains photographs of real, current astronomers and scientists working in astronomy and aerospace-related fields from many races, genders, cultural affiliations and walks of life. The photographs were taken and posters designed by Alyssa Trinh and Sarah Culp, high school interns in Discovery Corps, Pacific Science Center's youth development program. The direct contact between the scientists and the interns helps the intended audience of teachers and families personally connect with scientists. The finished posters from this exhibit are available online (http://pacificsciencecenter.org/scientists) for teachers to use in their classrooms, in addition to being displayed at Pacific Science Center and becoming part of Pacific Science Center's permanent art rotation. The objective of this project was to fill a need for representative photographs of scientists in the world community. It also met two of the goals of International Year of Astronomy: to provide a modern image of science and scientists, and to improve the gender-balanced representation of scientists at all levels and promote greater involvement by all people in scientific and engineering careers. We would like to build on the success of this project and create an annual summer internship, with different interns, focusing on creating posters for different fields of science.

  1. STS-26/Discovery Preparations for Launch

    NASA Technical Reports Server (NTRS)

    1988-01-01

    This NASA Kennedy Space Center two-part video release is comprised of footage covering STS-26 launch preparations from the arrival of the Tracking and Data Relay Satellite (TDRS) at the Orbiter Processing Facility (OPF) to the lift and mate of the external tanks. The STS-26 flight crew include: Frederick H. (Rick) Hauck, mission commander; Richard O. Covey, pilot; John M. (Mike) Lounge, mission specialist; David C. Hilmers, mission specialist; and George D. (Pinky) Nelson, mission specialist. The primary payload of STS-26 is the TDRS while the secondary payloads include the Physical Vapor Transport of Organic Solids (PVTOS); Protein Crystal Growth (PCG); Infrared Communications Flight Experiment (IRCFE); Aggregation of Red Blood Cells (ARC); Isoelectric Focusing Experiment (IFE); Mesoscale Lightning Experiment (MLE); Phase Partitioning Experiment (PPE); Earth-Limb Radiance Experiment (ELRAD); Automated Directional Solidification Furnace (ADSF) and two Shuttle Student Involvement Program (SSIP) experiments. Launch preparation footage includes flight crew arrival at KSC, rollout of Discovery to Pad B, OV-103 Discovery power-up, main engine unpacking and installation, solid rocket boosters' arrival prep and stacking, and aft skirt to aft segment mating.

  2. STS-26/Discovery Preparations for Launch

    NASA Technical Reports Server (NTRS)

    1988-01-01

    This NASA Kennedy Space Center two-part video release is comprised of footage covering STS-26 launch preparations from the arrival of the Tracking and Data Relay Satellite (TDRS) at the Orbiter Processing Facility (OPF) to the lift and mate of the external tanks. The STS-26 flight crew include: Frederick H. (Rick) Hauck, mission commander; Richard O. Covey, pilot; John M. (Mike) Lounge, mission specialist; David C. Hilmers, mission specialist; and George D. (Pinky) Nelson, mission specialist. The primary payload of STS-26 is the TDRS while the secondary payloads include the Physical Vapor Transport of Organic Solids (PVTOS); Protein Crystal Growth (PCG); Infrared Communications Flight Experiment (IRCFE); Aggregation of Red Blood Cells (ARC); Isoelectric Focusing Experiment (IFE); Mesoscale Lightning Experiment (MLE); Phase Partitioning Experiment (PPE); Earth-Limb Radiance Experiment (ELRAD); Automated Directional Solidification Furnace (ADSF) and two Shuttle Student Involvement Program (SSIP) experiments. Launch preparation footage includes flight crew arrival at KSC, rollout of Discovery to Pad B, OV-103 Discovery power-up, main engine unpacking and installation, solid rocket boosters' arrival prep and stacking, and aft skirt to aft segment mating.

  3. OPEN DATA FOR DISCOVERY SCIENCE.

    PubMed

    Payne, Philip R O; Huang, Kun; Shah, Nigam H; Tenenbaum, Jessica

    2016-01-01

    The modern healthcare and life sciences ecosystem is moving towards an increasingly open and data-centric approach to discovery science. This evolving paradigm is predicated on a complex set of information needs related to our collective ability to share, discover, reuse, integrate, and analyze open biological, clinical, and population level data resources of varying composition, granularity, and syntactic or semantic consistency. Such an evolution is further impacted by a concomitant growth in the size of data sets that can and should be employed for both hypothesis discovery and testing. When such open data can be accessed and employed for discovery purposes, a broad spectrum of high impact end-points is made possible. These span the spectrum from identification of de novo biomarker complexes that can inform precision medicine, to the repositioning or repurposing of extant agents for new and cost-effective therapies, to the assessment of population level influences on disease and wellness. Of note, these types of uses of open data can be either primary, wherein open data is the substantive basis for inquiry, or secondary, wherein open data is used to augment or enrich project-specific or proprietary data that is not open in and of itself. This workshop is concerned with the key challenges, opportunities, and methodological best practices whereby open data can be used to drive the advancement of discovery science in all of the aforementioned capacities.

  4. DISCOVERY IN THE URBAN SPRAWL.

    ERIC Educational Resources Information Center

    HYMOVITZ, LEON

    FOR A CULTURAL ENRICHMENT PROJECT ("DISCOVERY") IN A DISADVANTAGED PHILADELPIA HIGH SCHOOL, ATTENDANCE AT MUSIC, ART, AND THEATER EVENTS EARNED POINTS TOWARD A CERTIFICATE. THE STUDENTS ELECTED THE EVENTS FROM A PREPARED LIST OF ACTIVITIES, WHICH OFTEN WERE MADE PART OF THE ACADEMIC PROGRAM AND THE SCHOOL ASSEMBLIES. AS WELL AS OFFERING…

  5. Trends in Modern Drug Discovery.

    PubMed

    Eder, Jörg; Herrling, Paul L

    2016-01-01

    Drugs discovered by the pharmaceutical industry over the past 100 years have dramatically changed the practice of medicine and impacted on many aspects of our culture. For many years, drug discovery was a target- and mechanism-agnostic approach that was based on ethnobotanical knowledge often fueled by serendipity. With the advent of modern molecular biology methods and based on knowledge of the human genome, drug discovery has now largely changed into a hypothesis-driven target-based approach, a development which was paralleled by significant environmental changes in the pharmaceutical industry. Laboratories became increasingly computerized and automated, and geographically dispersed research sites are now more and more clustered into large centers to capture technological and biological synergies. Today, academia, the regulatory agencies, and the pharmaceutical industry all contribute to drug discovery, and, in order to translate the basic science into new medical treatments for unmet medical needs, pharmaceutical companies have to have a critical mass of excellent scientists working in many therapeutic fields, disciplines, and technologies. The imperative for the pharmaceutical industry to discover breakthrough medicines is matched by the increasing numbers of first-in-class drugs approved in recent years and reflects the impact of modern drug discovery approaches, technologies, and genomics.

  6. Structural Biology Guides Antibiotic Discovery

    ERIC Educational Resources Information Center

    Polyak, Steven

    2014-01-01

    Modern drug discovery programs require the contribution of researchers in a number of specialist areas. One of these areas is structural biology. Using X-ray crystallography, the molecular basis of how a drug binds to its biological target and exerts its mode of action can be defined. For example, a drug that binds into the active site of an…

  7. New approaches to antimicrobial discovery.

    PubMed

    Lewis, Kim

    2016-11-04

    The spread of resistant organisms is producing a human health crisis, as we are witnessing the emergence of pathogens resistant to all available antibiotics. An increase in chronic infections presents an additional challenge - these diseases are difficult to treat due to antibiotic-tolerant persister cells. Overmining of soil Actinomycetes ended the golden era of antibiotic discovery in the 60s, and efforts to replace this source by screening synthetic compound libraries was not successful. Bacteria have an efficient permeability barrier, preventing penetration of most synthetic compounds. Empirically establishing rules of penetration for antimicrobials will form the knowledge base to produce libraries tailored to antibiotic discovery, and will revive rational drug design. Two untapped sources of natural products hold the promise of reviving natural product discovery. Most bacterial species, over 99%, are uncultured, and methods to grow these organisms have been developed, and the first promising compounds are in development. Genome sequencing shows that known producers harbor many more operons coding for secondary metabolites than we can account for, providing an additional rich source of antibiotics. Revival of natural product discovery will require high-throughput identification of novel compounds within a large background of known substances. This could be achieved by rapid acquisition of transcription profiles from active extracts that will point to potentially novel compounds.

  8. Lowell Observatory's Discovery Channel Telescope

    NASA Astrophysics Data System (ADS)

    Hall, Jeffrey C.

    2017-01-01

    Lowell Observatory broke ground on its 4.3-meter Discovery Channel Telescope (DCT) in July 2005 and celebrated first light for the telescope in July 2012. In this overview to this special session, I will discuss the origin and development of the project, the telescope's general specifications and performance, its current operating status, and the initial instrument suite.

  9. Harry Stottlemier's Discovery [Revised Edition].

    ERIC Educational Resources Information Center

    Lipman, Matthew

    "Harry Stottlemeier's Discovery" is the student book for the project in philosophical thinking described in SO 008 123-126. It offers a model of dialogue -- both of children with one another and of children with adults. The story is set among a classroom of children who begin to understand the basics of logical reasoning when Harry, who isn't…

  10. The "Discovery" of Child Abuse

    ERIC Educational Resources Information Center

    Pfohl, Stephen J.

    1977-01-01

    Surveys the history of social reaction to child abuse, discusses the cultural values promoting the protection of children, points out how much pediatric radiology benefited from its "discovery" of "the battered child syndrome" in the early sixties, and concludes that the labeling of child abusers as "sick" has shielded them from criminal…

  11. Illinois Birds. Nature Discovery I.

    ERIC Educational Resources Information Center

    Stone, Sally F.

    The birds of Illinois and their particular habitats are explored in this guide which is a part of a series of Nature Discovery publications. The materials are designed to directly supplement the natural science curricula and to complement other subject areas including social studies, language arts, music, and art. The program is formated for…

  12. The "Discovery" of Child Abuse

    ERIC Educational Resources Information Center

    Pfohl, Stephen J.

    1977-01-01

    Surveys the history of social reaction to child abuse, discusses the cultural values promoting the protection of children, points out how much pediatric radiology benefited from its "discovery" of "the battered child syndrome" in the early sixties, and concludes that the labeling of child abusers as "sick" has shielded them from criminal…

  13. Communication in Collaborative Discovery Learning

    ERIC Educational Resources Information Center

    Saab, Nadira; van Joolingen, Wouter R.; van Hout-Wolters, Bernadette H. A. M.

    2005-01-01

    Background: Constructivist approaches to learning focus on learning environments in which students have the opportunity to construct knowledge themselves, and negotiate this knowledge with others. "Discovery learning" and "collaborative learning" are examples of learning contexts that cater for knowledge construction processes. We introduce a…

  14. Arnold on Discovery Flightdeck (FD)

    NASA Image and Video Library

    2009-03-16

    S119-E-005010 (15 March 2009) --- Astronaut Richard Arnold, STS-119 mission specialist, attired in his shuttle launch and entry suit, gives a “thumbs-up” signal on the aft flight deck of Space Shuttle Discovery during postlaunch activities.

  15. Supporting Discovery in Virtual Libraries.

    ERIC Educational Resources Information Center

    Desai, Bipin C.

    1997-01-01

    Discussion of models for indexing and searching information resources on the Internet focuses on the results of a simple query on a number of existing search systems and on two proposed index metadata structures for indexing and supporting search and discovery: the Dublin Core Elements List and the Semantic Header. (52 references) (Author/LRW)

  16. Illinois Birds. Nature Discovery I.

    ERIC Educational Resources Information Center

    Stone, Sally F.

    The birds of Illinois and their particular habitats are explored in this guide which is a part of a series of Nature Discovery publications. The materials are designed to directly supplement the natural science curricula and to complement other subject areas including social studies, language arts, music, and art. The program is formated for…

  17. Communication in Collaborative Discovery Learning

    ERIC Educational Resources Information Center

    Saab, Nadira; van Joolingen, Wouter R.; van Hout-Wolters, Bernadette H. A. M.

    2005-01-01

    Background: Constructivist approaches to learning focus on learning environments in which students have the opportunity to construct knowledge themselves, and negotiate this knowledge with others. "Discovery learning" and "collaborative learning" are examples of learning contexts that cater for knowledge construction processes. We introduce a…

  18. Discovery Learning in Landscape Archaeology.

    ERIC Educational Resources Information Center

    O'Brien, Colm; Wheeler, Hazel

    1979-01-01

    A method of discovery learning in which students learn the technique of observing and formulating questions is applied to landscape archaeology. This method demands that the relationship between tutor and student be adjusted so that the tutor becomes a fellow researcher rather than a conveyor of information. (Author/CSS)

  19. Structural Biology Guides Antibiotic Discovery

    ERIC Educational Resources Information Center

    Polyak, Steven

    2014-01-01

    Modern drug discovery programs require the contribution of researchers in a number of specialist areas. One of these areas is structural biology. Using X-ray crystallography, the molecular basis of how a drug binds to its biological target and exerts its mode of action can be defined. For example, a drug that binds into the active site of an…

  20. [Activity of NTDs Drug-discovery Research Consortium].

    PubMed

    Namatame, Ichiji

    2016-01-01

    Neglected tropical diseases (NTDs) are an extremely important issue facing global health care. To improve "access to health" where people are unable to access adequate medical care due to poverty and weak healthcare systems, we have established two consortiums: the NTD drug discovery research consortium, and the pediatric praziquantel consortium. The NTD drug discovery research consortium, which involves six institutions from industry, government, and academia, as well as an international non-profit organization, is committed to developing anti-protozoan active compounds for three NTDs (Leishmaniasis, Chagas disease, and African sleeping sickness). Each participating institute will contribute their efforts to accomplish the following: selection of drug targets based on information technology, and drug discovery by three different approaches (in silico drug discovery, "fragment evolution" which is a unique drug designing method of Astellas Pharma, and phenotypic screening with Astellas' compound library). The consortium has established a brand new database (Integrated Neglected Tropical Disease Database; iNTRODB), and has selected target proteins for the in silico and fragment evolution drug discovery approaches. Thus far, we have identified a number of promising compounds that inhibit the target protein, and we are currently trying to improve the anti-protozoan activity of these compounds. The pediatric praziquantel consortium was founded in July 2012 to develop and register a new praziquantel pediatric formulation for the treatment of schistosomiasis. Astellas Pharma has been a core member in this consortium since its establishment, and has provided expertise and technology in the area of pediatric formulation development and clinical development.

  1. The role of epidemic infectious diseases in the discovery of America.

    PubMed

    Bianchine, P J; Russo, T A

    1992-01-01

    As the world prepares to celebrate the quincentennial events surrounding the discovery of the New World by Christopher Columbus in 1492, a particular interest regarding the influence of epidemic infectious diseases on the history of the conquest of America has emerged. Contrary to popular belief, it was not the European guns or fierce soldiers that conquered the native Americans, but instead it was the common childhood illnesses brought from the Old World by the European conquistadors. Diseases such as smallpox, measles, and typhus annihilated most of the American native populations. Devastating epidemics resulted throughout the New World. We will review the consequences of introducing new infectious agents into a nonimmune population, discuss the major pathogens that were imported from the Old World, and focus on how these diseases may have affected the aboriginal depopulation of the Americas.

  2. Advances in Lipidomics for Cancer Biomarkers Discovery

    PubMed Central

    Perrotti, Francesca; Rosa, Consuelo; Cicalini, Ilaria; Sacchetta, Paolo; Del Boccio, Piero; Genovesi, Domenico; Pieragostino, Damiana

    2016-01-01

    Lipids play critical functions in cellular survival, proliferation, interaction and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell–cell interactions. These cellular processes are strongly related to carcinogenesis pathways, particularly to transformation, progression, and metastasis, suggesting the bioactive lipids are mediators of a number of oncogenic processes. The current review gives a synopsis of a lipidomic approach in tumor characterization; we provide an overview on potential lipid biomarkers in the oncology field and on the principal lipidomic methodologies applied. The novel lipidomic biomarkers are reviewed in an effort to underline their role in diagnosis, in prognostic characterization and in prediction of therapeutic outcomes. A lipidomic investigation through mass spectrometry highlights new insights on molecular mechanisms underlying cancer disease. This new understanding will promote clinical applications in drug discovery and personalized therapy. PMID:27916803

  3. Recent discoveries and applications of Anoxybacillus.

    PubMed

    Goh, Kian Mau; Kahar, Ummirul Mukminin; Chai, Yen Yen; Chong, Chun Shiong; Chai, Kian Piaw; Ranjani, Velayudhan; Illias, Rosli; Chan, Kok-Gan

    2013-02-01

    The Bacillaceae family members are a good source of bacteria for bioprocessing and biotransformation involving whole cells or enzymes. In contrast to Bacillus and Geobacillus, Anoxybacillus is a relatively new genus that was proposed in the year 2000. Because these bacteria are alkali-tolerant thermophiles, they are suitable for many industrial applications. More than a decade after the first report of Anoxybacillus, knowledge accumulated from fundamental and applied studies suggests that this genus can serve as a good alternative in many applications related to starch and lignocellulosic biomasses, environmental waste treatment, enzyme technology, and possibly bioenergy production. This current review provides the first summary of past and recent discoveries regarding the isolation of Anoxybacillus, its medium requirements, its proteins that have been characterized and cloned, bioremediation applications, metabolic studies, and genomic analysis. Comparisons to some other members of Bacillaceae and possible future applications of Anoxybacillus are also discussed.

  4. A metadata initiative for global information discovery

    USGS Publications Warehouse

    Christian, E.

    2001-01-01

    The Global Information Locator Service (GILS) encompasses a global vision framed by the fundamental values of open societies. Societal values such as a free flow of information impose certain requirements on the society's information infrastructure. These requirements in turn shape the various laws, policies, standards, and technologies that determine the infrastructure design. A particular focus of GILS is the requirement to provide the means for people to discover sources of data and information. Information discovery in the GILS vision is designed to be decentralized yet coherent, and globally comprehensive yet useful for detailed data. This article introduces basic concepts and design issues, with emphasis on the techniques by which GILS supports interoperability. It explains the practical implications of GILS for the common roles of organizations involved in handling information, from content provider through system engineer and intermediary to searcher. The article provides examples of GILS initiatives in various types of communities: bibliographic, geographic, environmental, and government. ?? 2001 Elsevier Science Inc.

  5. [Novel targets for antibiotics discovery: riboswitches].

    PubMed

    Jia, Dong-fang; Jia, Dong-fang; Jia, Dong-fang

    2013-09-01

    Riboswitches are cis-acting domains located in mRNA sequences that could regulate gene expression by sensing small molecules without employing protein. Most known riboswitches in bacteria have naturally evolved to bind essential metabolite ligands and are involved in the regulation of critical genes that are responsible for the biosynthesis or transport of the cognate ligand. The riboswitch-mediated gene expression could be repressed by metabolite analogs, which caused bacterial growth inhibition or even death. A number of leading compounds targeting riboswitches have been discovered. A promising avenue for the development of new class of riboswitch-based antibiotics has been opened. Herein we reviewed the current findings of riboswitches that served as targets for antibacterial drug development and the underlying mechanisms. The development of high-throughput methods and rational drug design for riboswitch-specific drug discovery are relevant challenges are discussed. summarized.

  6. Selection effects in the discovery of NEAs

    NASA Astrophysics Data System (ADS)

    Valsecchi, G. B.; D'Abramo, G.; Boattini, A.

    2015-03-01

    To highlight discovery selection effects, we consider four NEA subpopulations: (a) ``Taurid asteroids'', the Apollos with orbits similar to those of 2P/Encke and of the Taurid meteoroid complex; (b) Atens, to which we add the Inner Earth Objects; (c) non-Taurid Apollos; (d) Amors. The ``Taurid asteroids`` are identified by Asher et al. (1993) with a reduced version of the D-criterion (Southworth and Hawkins 1963), involving only a, e and i: \\begin{displaymath}D=\\sqrt{\\left(\\frac{a-2.1}{3}\\right)^2+(e-0.82)^2+\\left(2\\sin{\\frac{i-4^\\circ}{2}}\\right)^2}\\leq0.25.\\end{displaymath} It turns out that the distribution of the longitudes of perihelion ϖ of NEAs with D<0.25 is significantly non-random, due to the existence of two groups whose apse lines are approximately aligned with those of 2P/Encke and of (2212) Hephaistos.

  7. 37 CFR 41.150 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... parties may agree to discovery among themselves at any time. (b) Automatic discovery. (1) Within 21 days... requested material is in a language other than English, a translation, if available, and (ii) File with the...

  8. Arthritis Genetics Analysis Aids Drug Discovery

    MedlinePlus

    ... Research Matters January 13, 2014 Arthritis Genetics Analysis Aids Drug Discovery An international research team identified 42 ... Distracted Driving Raises Crash Risk Arthritis Genetics Analysis Aids Drug Discovery Oxytocin Affects Facial Recognition Connect with ...

  9. Phenotypic Assessment and the Discovery of Topiramate

    PubMed Central

    2016-01-01

    The role of phenotypic assessment in drug discovery is discussed, along with the discovery and development of TOPAMAX (topiramate), a billion-dollar molecule for the treatment of epilepsy and migraine. PMID:27437073

  10. 36 CFR 1150.63 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... discovery and issue orders including orders—(1) to submit testimony upon oral examination or written... for discovery shall be granted only to the extent and upon such terms as the judge in his/her...

  11. 6 CFR 13.21 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Document or of the truth of any relevant fact; (iii) Written interrogatories; and (iv) Depositions. (2... the creation of a Document. (c) Motions for discovery. (1) A party seeking discovery may file a...

  12. Quantifying the Ease of Scientific Discovery.

    PubMed

    Arbesman, Samuel

    2011-02-01

    It has long been known that scientific output proceeds on an exponential increase, or more properly, a logistic growth curve. The interplay between effort and discovery is clear, and the nature of the functional form has been thought to be due to many changes in the scientific process over time. Here I show a quantitative method for examining the ease of scientific progress, another necessary component in understanding scientific discovery. Using examples from three different scientific disciplines - mammalian species, chemical elements, and minor planets - I find the ease of discovery to conform to an exponential decay. In addition, I show how the pace of scientific discovery can be best understood as the outcome of both scientific output and ease of discovery. A quantitative study of the ease of scientific discovery in the aggregate, such as done here, has the potential to provide a great deal of insight into both the nature of future discoveries and the technical processes behind discoveries in science.

  13. 13 CFR 134.310 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... OFFICE OF HEARINGS AND APPEALS Rules of Practice for Appeals From Size Determinations and NAICS Code Designations § 134.310 Discovery. Discovery will not be permitted in appeals from size determinations or NAICS...

  14. 24 CFR 180.500 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SECRETARY FOR EQUAL OPPORTUNITY, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT EMPLOYMENT AND BUSINESS OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a)...

  15. 31 CFR 10.71 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... law; (7) The material sought relates to mental impressions, conclusions, or legal theories of any... information from evidence or issue a decision by default. (f) Other discovery. No discovery other than...

  16. Shuttle Discovery Landing at Edwards

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The STS-29 Space Shuttle Discovery mission lands at NASA's then Ames-Dryden Flight Research Facility, Edwards AFB, California, early Saturday morning, 18 March 1989. Touchdown was at 6:35:49 a.m. PST and wheel stop was at 6:36:40 a.m. on runway 22. Controllers chose the concrete runway for the landing in order to make tests of braking and nosewheel steering. The STS-29 mission was very successful, completing the launch of a Tracking and Data Relay communications satellite, as well as a range of scientific experiments. Discovery's five-man crew was led by Commander Michael L. Coats, and included pilot John E. Blaha and mission specialists James P. Bagian, Robert C. Springer, and James F. Buchli. Space Shuttles are the main element of America's Space Transportation System and are used for space research and other space applications. The shuttles are the first vehicles capable of being launched into space and returning to Earth on a routine basis. Space Shuttles are used as orbiting laboratories in which scientists and mission specialists conduct a wide variety of scientific experiments. Crews aboard shuttles place satellites in orbit, rendezvous with satellites to carry out repair missions and return them to space, and retrieve satellites and return them to Earth for refurbishment and reuse. Space Shuttles are true aerospace vehicles. They leave Earth and its atmosphere under rocket power provided by three liquid-propellant main engines with two solid-propellant boosters attached plus an external liquid-fuel tank. After their orbital missions, they streak back through the atmosphere and land like airplanes. The returning shuttles, however, land like gliders, without power and on runways. Other rockets can place heavy payloads into orbit, but, they can only be used once. Space Shuttles are designed to be continually reused. When Space Shuttles are used to transport complete scientific laboratories into space, the laboratories remain inside the payload bay throughout

  17. Should there be a three-strikes rule against pure discovery learning? The case for guided methods of instruction.

    PubMed

    Mayer, Richard E

    2004-01-01

    The author's thesis is that there is sufficient research evidence to make any reasonable person skeptical about the benefits of discovery learning--practiced under the guise of cognitive constructivism or social constructivism--as a preferred instructional method. The author reviews research on discovery of problem-solving rules culminating in the 1960s, discovery of conservation strategies culminating in the 1970s, and discovery of LOGO programming strategies culminating in the 1980s. In each case, guided discovery was more effective than pure discovery in helping students learn and transfer. Overall, the constructivist view of learning may be best supported by methods of instruction that involve cognitive activity rather than behavioral activity, instructional guidance rather than pure discovery, and curricular focus rather than unstructured exploration.

  18. Hypertrophic and Dilated Cardiomyopathy: Four Decades of Basic Research on Muscle Lead to Potential Therapeutic Approaches to These Devastating Genetic Diseases

    PubMed Central

    Spudich, James A.

    2014-01-01

    With the advent of technologies to obtain the complete sequence of the human genome in a cost-effective manner, this decade and those to come will see an exponential increase in our understanding of the underlying genetics that lead to human disease. And where we have a deep understanding of the biochemical and biophysical basis of the machineries and pathways involved in those genetic changes, there are great hopes for the development of modern therapeutics that specifically target the actual machinery and pathways altered by individual mutations. Prime examples of such a genetic disease are those classes of hypertrophic and dilated cardiomyopathy that result from single amino-acid substitutions in one of several of the proteins that make up the cardiac sarcomere or from the truncation of myosin binding protein C. Hypertrophic cardiomyopathy alone affects ∼1 in 500 individuals, and it is the leading cause of sudden cardiac death in young adults. Here I describe approaches to understand the molecular basis of the alterations in power output that result from these mutations. Small molecules binding to the mutant sarcomeric protein complex should be able to mitigate the effects of hypertrophic and dilated cardiomyopathy mutations at their sources, leading to possible new therapeutic approaches for these genetic diseases. PMID:24655499

  19. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases.

    PubMed

    Spudich, James A

    2014-03-18

    With the advent of technologies to obtain the complete sequence of the human genome in a cost-effective manner, this decade and those to come will see an exponential increase in our understanding of the underlying genetics that lead to human disease. And where we have a deep understanding of the biochemical and biophysical basis of the machineries and pathways involved in those genetic changes, there are great hopes for the development of modern therapeutics that specifically target the actual machinery and pathways altered by individual mutations. Prime examples of such a genetic disease are those classes of hypertrophic and dilated cardiomyopathy that result from single amino-acid substitutions in one of several of the proteins that make up the cardiac sarcomere or from the truncation of myosin binding protein C. Hypertrophic cardiomyopathy alone affects ∼1 in 500 individuals, and it is the leading cause of sudden cardiac death in young adults. Here I describe approaches to understand the molecular basis of the alterations in power output that result from these mutations. Small molecules binding to the mutant sarcomeric protein complex should be able to mitigate the effects of hypertrophic and dilated cardiomyopathy mutations at their sources, leading to possible new therapeutic approaches for these genetic diseases.

  20. 39 CFR 963.14 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Discovery. 963.14 Section 963.14 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO VIOLATIONS OF THE PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a...

  1. 37 CFR 2.120 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... develop a disclosure and discovery plan, the scope, timing and sequence of discovery, protective orders.... The trial order setting these deadlines and dates will be included with the notice of institution of... resetting disclosure, discovery or trial dates. If the expert is retained after the deadline for disclosure...

  2. 37 CFR 2.120 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... develop a disclosure and discovery plan, the scope, timing and sequence of discovery, protective orders.... The trial order setting these deadlines and dates will be included with the notice of institution of... resetting disclosure, discovery or trial dates. If the expert is retained after the deadline for disclosure...

  3. 10 CFR 13.21 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Discovery. 13.21 Section 13.21 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests for...

  4. 10 CFR 205.198 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Discovery. 205.198 Section 205.198 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Notice of Probable Violation, Remedial Order, Notice... Motions for Discovery and related filings must be served upon the person to whom the discovery is...

  5. 10 CFR 205.198 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Discovery. 205.198 Section 205.198 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Notice of Probable Violation, Remedial Order, Notice... Motions for Discovery and related filings must be served upon the person to whom the discovery is...

  6. 42 CFR 426.432 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... discovery via a request for the production of documents, and/or via the submission of up to 10 written... creation of a document. (e) Types of discovery not available. Requests for admissions, depositions, or any... all parties in writing when the discovery period closes....

  7. 42 CFR 426.432 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... discovery via a request for the production of documents, and/or via the submission of up to 10 written... creation of a document. (e) Types of discovery not available. Requests for admissions, depositions, or any... all parties in writing when the discovery period closes....

  8. 49 CFR 1503.633 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... any time after a complaint has been filed in the proceedings. (b) Methods of discovery. The following... agency or any agency employee on the agency attorney of record. (d) Time for response to discovery... discovery set forth in paragraph (f) of this section, a party may discover any matter that is not...

  9. Discovery in Science and in Teaching Science

    ERIC Educational Resources Information Center

    Kipnis, Nahum

    2007-01-01

    A proper presentation of scientific discoveries may allow science teachers to eliminate certain myths about the nature of science, which originate from an uncertainty among scholars about what constitutes a discovery. It is shown that a disagreement on this matter originates from a confusion of the act of discovery with response to it. It is…

  10. Discovery in Science and in Teaching Science

    ERIC Educational Resources Information Center

    Kipnis, Nahum

    2007-01-01

    A proper presentation of scientific discoveries may allow science teachers to eliminate certain myths about the nature of science, which originate from an uncertainty among scholars about what constitutes a discovery. It is shown that a disagreement on this matter originates from a confusion of the act of discovery with response to it. It is…

  11. 29 CFR 2700.56 - Discovery; general.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... interrogatories; or requests for admissions, for production of documents or objects or for permission to enter... likely to lead to the discovery of admissible evidence. (c) Limitation of discovery. Upon motion by a party or by the person from whom discovery is sought or upon his own motion, a Judge may, for good cause...

  12. 29 CFR 2700.56 - Discovery; general.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... interrogatories; or requests for admissions, for production of documents or objects or for permission to enter... likely to lead to the discovery of admissible evidence. (c) Limitation of discovery. Upon motion by a party or by the person from whom discovery is sought or upon his own motion, a Judge may, for good cause...

  13. 45 CFR 150.435 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) A party to whom a discovery request is directed may object in writing for any of the following... document must state why the nonprivileged part is not segregable. (e) Any motion to compel discovery must... 10 days after receipt of an incomplete response to the discovery request. The motion must be...

  14. 45 CFR 150.435 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) A party to whom a discovery request is directed may object in writing for any of the following... document must state why the nonprivileged part is not segregable. (e) Any motion to compel discovery must... 10 days after receipt of an incomplete response to the discovery request. The motion must be...

  15. 29 CFR 2700.56 - Discovery; general.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... interrogatories; or requests for admissions, for production of documents or objects or for permission to enter... likely to lead to the discovery of admissible evidence. (c) Limitation of discovery. Upon motion by a party or by the person from whom discovery is sought or upon his own motion, a Judge may, for good cause...

  16. 14 CFR 13.220 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... scope of discovery requested by the party is unduly burdensome or expensive. (g) Confidential orders. A... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery....

  17. 14 CFR 13.220 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... scope of discovery requested by the party is unduly burdensome or expensive. (g) Confidential orders. A... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery....

  18. 36 CFR 1150.63 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for discovery, and provisions for protecting the secrecy of confidential information or documents. If... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Discovery. 1150.63 Section... PRACTICE AND PROCEDURES FOR COMPLIANCE HEARINGS Prehearing Conferences and Discovery § 1150.63...

  19. 36 CFR 1150.63 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for discovery, and provisions for protecting the secrecy of confidential information or documents. If... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Discovery. 1150.63 Section... PRACTICE AND PROCEDURES FOR COMPLIANCE HEARINGS Prehearing Conferences and Discovery § 1150.63...

  20. 7 CFR 1.322 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Discovery. 1.322 Section 1.322 Agriculture Office of... Under the Program Fraud Civil Remedies Act of 1986 § 1.322 Discovery. (a) The following types of discovery are authorized: (1) Requests for production, inspection and photocopying of documents;...

  1. 36 CFR 1150.63 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for discovery, and provisions for protecting the secrecy of confidential information or documents. If... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Discovery. 1150.63 Section... PRACTICE AND PROCEDURES FOR COMPLIANCE HEARINGS Prehearing Conferences and Discovery § 1150.63...

  2. 15 CFR 785.8 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Discovery. 785.8 Section 785.8... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter,...

  3. 15 CFR 785.8 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Discovery. 785.8 Section 785.8... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter,...

  4. 15 CFR 785.8 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 785.8 Section 785.8... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter,...

  5. 49 CFR 1503.633 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... who any other party expects to call to testify at the hearing. A party may not object to a discovery... matters during discovery. (j) Duty to supplement or amend responses. A party who has responded to a discovery request has a duty to supplement or amend the response, as soon as the information is known, as...

  6. 39 CFR 963.14 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Discovery. 963.14 Section 963.14 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO VIOLATIONS OF THE PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a...

  7. 39 CFR 963.14 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Discovery. 963.14 Section 963.14 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO VIOLATIONS OF THE PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a...

  8. 39 CFR 963.14 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Discovery. 963.14 Section 963.14 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO VIOLATIONS OF THE PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a...

  9. 39 CFR 963.14 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Discovery. 963.14 Section 963.14 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE IN PROCEEDINGS RELATIVE TO VIOLATIONS OF THE PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a...

  10. Does Discovery-Based Instruction Enhance Learning?

    ERIC Educational Resources Information Center

    Alfieri, Louis; Brooks, Patricia J.; Aldrich, Naomi J.; Tenenbaum, Harriet R.

    2011-01-01

    Discovery learning approaches to education have recently come under scrutiny (Tobias & Duffy, 2009), with many studies indicating limitations to discovery learning practices. Therefore, 2 meta-analyses were conducted using a sample of 164 studies: The 1st examined the effects of unassisted discovery learning versus explicit instruction, and the…

  11. 29 CFR 18.13 - Discovery methods.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Discovery methods. 18.13 Section 18.13 Labor Office of the... ADMINISTRATIVE LAW JUDGES General § 18.13 Discovery methods. Parties may obtain discovery by one or more of the following methods: Depositions upon oral examination or written questions; written...

  12. 49 CFR 386.37 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Discovery. 386.37 Section 386.37 Transportation... and Hearings § 386.37 Discovery. (a) Parties may obtain discovery by one or more of the following methods: Depositions upon oral examination or written questions; written interrogatories; request...

  13. 45 CFR 99.23 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROCEDURE FOR HEARINGS FOR THE CHILD CARE AND... groups recognized as parties shall have the right to conduct discovery (including depositions) against... discovery is sought and to restrict or control discovery so as to prevent undue delay in the conduct of...

  14. 38 CFR 42.21 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Discovery. 42.21 Section 42.21 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) STANDARDS IMPLEMENTING THE PROGRAM FRAUD CIVIL REMEDIES ACT § 42.21 Discovery. (a) The following types of discovery...

  15. 38 CFR 42.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Discovery. 42.21 Section 42.21 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) STANDARDS IMPLEMENTING THE PROGRAM FRAUD CIVIL REMEDIES ACT § 42.21 Discovery. (a) The following types of discovery...

  16. Materials discovery via CALYPSO methodology

    NASA Astrophysics Data System (ADS)

    Wang, Yanchao; Lv, Jian; Zhu, Li; Lu, Shaohua; Yin, Ketao; Li, Quan; Wang, Hui; Zhang, Lijun; Ma, Yanming

    2015-05-01

    The structure prediction at the atomic level is emerging as a state-of-the-art approach to accelerate the functionality-driven discovery of materials. By combining the global swarm optimization algorithm with first-principles thermodynamic calculations, it exploits the power of current supercomputer architectures to robustly predict the ground state and metastable structures of materials with only the given knowledge of chemical composition. In this Review, we provide an overview of the basic theory and main features of our as-developed CALYPSO structure prediction method, as well as its versatile applications to design of a broad range of materials including those of three-dimensional bulks, two-dimensional reconstructed surfaces and layers, and isolated clusters/nanoparticles or molecules with a variety of functional properties. The current challenges faced by structure prediction for materials discovery and future developments of CALYPSO to overcome them are also discussed.

  17. Shuttle Discovery Landing at Edwards

    NASA Image and Video Library

    1989-03-18

    The STS-29 Space Shuttle Discovery mission lands at NASA's then Ames-Dryden Flight Research Facility, Edwards AFB, California, early Saturday morning, 18 March 1989. Touchdown was at 6:35:49 a.m. PST and wheel stop was at 6:36:40 a.m. on runway 22. Controllers chose the concrete runway for the landing in order to make tests of braking and nosewheel steering. The STS-29 mission was very successful, completing the launch of a Tracking and Data Relay communications satellite, as well as a range of scientific experiments. Discovery's five-man crew was led by Commander Michael L. Coats, and included pilot John E. Blaha and mission specialists James P. Bagian, Robert C. Springer, and James F. Buchli.

  18. Metagenomics and novel gene discovery

    PubMed Central

    Culligan, Eamonn P; Sleator, Roy D; Marchesi, Julian R; Hill, Colin

    2014-01-01

    Metagenomics provides a means of assessing the total genetic pool of all the microbes in a particular environment, in a culture-independent manner. It has revealed unprecedented diversity in microbial community composition, which is further reflected in the encoded functional diversity of the genomes, a large proportion of which consists of novel genes. Herein, we review both sequence-based and functional metagenomic methods to uncover novel genes and outline some of the associated problems of each type of approach, as well as potential solutions. Furthermore, we discuss the potential for metagenomic biotherapeutic discovery, with a particular focus on the human gut microbiome and finally, we outline how the discovery of novel genes may be used to create bioengineered probiotics. PMID:24317337

  19. Discovery STS-131 Mission Landing

    NASA Image and Video Library

    2010-04-20

    STS131-S-091 (20 April 2010) --- NASA Deputy Administrator Lori Garver and NASA astronaut Alan Poindexter, STS-131 commander, walk around under the space shuttle Discovery shortly after Discovery and its seven-member crew landed at the Kennedy Space Center in Cape Canaveral, Fla., on April 20, 2010. Poindexter and NASA astronaut James P. Dutton Jr., pilot; along with NASA astronauts Dorothy Metcalf-Lindenburger, Rick Mastracchio, Stephanie Wilson, Clayton Anderson and Japanese astronaut Naoko Yamazaki, all mission specialists, returned from their 15-day journey of more than 6.2 million miles. The STS-131 mission to the International Space Station delivered science racks, new crew sleeping quarters, equipment and supplies. Photo credit: NASA/Bill Ingalls

  20. Discovery of essential fatty acids

    PubMed Central

    Spector, Arthur A.; Kim, Hee-Yong

    2015-01-01

    Dietary fat was recognized as a good source of energy and fat-soluble vitamins by the first part of the 20th century, but fatty acids were not considered to be essential nutrients because they could be synthesized from dietary carbohydrate. This well-established view was challenged in 1929 by George and Mildred Burr who reported that dietary fatty acid was required to prevent a deficiency disease that occurred in rats fed a fat-free diet. They concluded that fatty acids were essential nutrients and showed that linoleic acid prevented the disease and is an essential fatty acid. The Burrs surmised that other unsaturated fatty acids were essential and subsequently demonstrated that linolenic acid, the omega-3 fatty acid analog of linoleic acid, is also an essential fatty acid. The discovery of essential fatty acids was a paradigm-changing finding, and it is now considered to be one of the landmark discoveries in lipid research. PMID:25339684

  1. Principles of early drug discovery

    PubMed Central

    Hughes, JP; Rees, S; Kalindjian, SB; Philpott, KL

    2011-01-01

    Developing a new drug from original idea to the launch of a finished product is a complex process which can take 12–15 years and cost in excess of $1 billion. The idea for a target can come from a variety of sources including academic and clinical research and from the commercial sector. It may take many years to build up a body of supporting evidence before selecting a target for a costly drug discovery programme. Once a target has been chosen, the pharmaceutical industry and more recently some academic centres have streamlined a number of early processes to identify molecules which possess suitable characteristics to make acceptable drugs. This review will look at key preclinical stages of the drug discovery process, from initial target identification and validation, through assay development, high throughput screening, hit identification, lead optimization and finally the selection of a candidate molecule for clinical development. PMID:21091654

  2. Principles of early drug discovery.

    PubMed

    Hughes, J P; Rees, S; Kalindjian, S B; Philpott, K L

    2011-03-01

    Developing a new drug from original idea to the launch of a finished product is a complex process which can take 12-15 years and cost in excess of $1 billion. The idea for a target can come from a variety of sources including academic and clinical research and from the commercial sector. It may take many years to build up a body of supporting evidence before selecting a target for a costly drug discovery programme. Once a target has been chosen, the pharmaceutical industry and more recently some academic centres have streamlined a number of early processes to identify molecules which possess suitable characteristics to make acceptable drugs. This review will look at key preclinical stages of the drug discovery process, from initial target identification and validation, through assay development, high throughput screening, hit identification, lead optimization and finally the selection of a candidate molecule for clinical development.

  3. Materials discovery via CALYPSO methodology.

    PubMed

    Wang, Yanchao; Lv, Jian; Zhu, Li; Lu, Shaohua; Yin, Ketao; Li, Quan; Wang, Hui; Zhang, Lijun; Ma, Yanming

    2015-05-27

    The structure prediction at the atomic level is emerging as a state-of-the-art approach to accelerate the functionality-driven discovery of materials. By combining the global swarm optimization algorithm with first-principles thermodynamic calculations, it exploits the power of current supercomputer architectures to robustly predict the ground state and metastable structures of materials with only the given knowledge of chemical composition. In this Review, we provide an overview of the basic theory and main features of our as-developed CALYPSO structure prediction method, as well as its versatile applications to design of a broad range of materials including those of three-dimensional bulks, two-dimensional reconstructed surfaces and layers, and isolated clusters/nanoparticles or molecules with a variety of functional properties. The current challenges faced by structure prediction for materials discovery and future developments of CALYPSO to overcome them are also discussed.

  4. Enteric Neurobiology: Discoveries and Directions.

    PubMed

    Wood, Jackie D

    Discovery and documentation of noncholinergic-nonadrenergic neurotransmission in the enteric nervous system started a revolution in mechanisms of neural control of the digestive tract that continues into a twenty-first century era of translational gastroenterology, which is now firmly embedded in the term, neurogastroenterology. This chapter, on Enteric Neurobiology: Discoveries and Directions, tracks the step-by-step advances in enteric neuronal electrophysiology and synaptic behavior and progresses to the higher order functions of central pattern generators, hard wired synaptic circuits and libraries of neural programs in the brain-in-the-gut that underlie the several different patterns of motility and secretory behaviors that occur in the specialized, serially-connected compartments extending from the esophagus to the anus.

  5. Chlorophyll: anatomy of a discovery

    SciTech Connect

    Rebeiz, C.A.

    1982-01-01

    Observations were made that are incompatible with the conventional visualization of the biosynthesis of chlorophyll, such as the pathway proposed by S. Granick. The new discoveries were made possible by techniques developed by the author: cell-free systems capable of synthesizing protochlorophyll and chlorophyll a and b from /delta/-aminolevulinic acid; the use of radio isotopes; and spectrofluorometric techniques. An understanding of the different chlorophyll chemical structures is essential to the technology of capturing solar energy. 53 refs.

  6. Fast Anomaly Discovery Given Duplicates

    DTIC Science & Technology

    2012-12-01

    skipping the computations for duplicate points in SN(ui) that have ci larger than k, the runtime complexity is enhanced significantly. That is, in...Fast anomaly discovery given duplicates Jay-Yoon Lee, U Kang, Danai Koutra, Christos Faloutsos Dec 2012 CMU-CS-12-146 School of Computer Science...ES) Carnegie Mellon University,School of Computer Science,Pittsburgh,PA,15213 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING

  7. STS-121 Discovery Tail Section

    NASA Technical Reports Server (NTRS)

    2006-01-01

    A close-up view of Space Shuttle Discovery's tail section is featured in this image photographed by an Expedition 13 crew member on the International Space Station (ISS) during the STS-121 Rendezvous Prior to Mating (RPM) survey. Visible are the space shuttle's main engines (SSME), vertical stabilizer, orbital maneuvering system (OMS) pods and a portion of the aft cargo bay and wings. The Marshall Space Flight Center (MSFC) has management responsibility for development of the SSME.

  8. Discovery of a Makemakean Moon

    NASA Technical Reports Server (NTRS)

    Parker, Alex H.; Buie, Marc W.; Grundy, Will M.; Noll, Keith S.

    2016-01-01

    We describe the discovery of a satellite in orbit about the dwarf planet (136472) Makemake. This satellite, provisionally designated S/2015 (136472) 1, was detected in imaging data collected with the Hubble Space Telescope's Wide Field Camera 3 on UTC 2015 April 27 at 7.80 +/- 0.04 mag fainter than Makemake and at a separation of 0farcs57. It likely evaded detection in previous satellite searches due to a nearly edge-on orbital configuration, placing it deep within the glare of Makemake during a substantial fraction of its orbital period. This configuration would place Makemake and its satellite near a mutual event season. Insufficient orbital motion was detected to make a detailed characterization of its orbital properties, prohibiting a measurement of the system mass with the discovery data alone. Preliminary analysis indicates that if the orbit is circular, its orbital period must be longer than 12.4 days and must have a semimajor axis > or approx. = 21,000 km. We find that the properties of Makemake's moon suggest that the majority of the dark material detected in the system by thermal observations may not reside on the surface of Makemake, but may instead be attributable to S/2015 (136472) 1 having a uniform dark surface. This dark moon hypothesis can be directly tested with future James Webb Space Telescope observations. We discuss the implications of this discovery for the spin state, figure, and thermal properties of Makemake and the apparent ubiquity of trans-Neptunian dwarf planet satellites.

  9. Five Years of GWAS Discovery

    PubMed Central

    Visscher, Peter M.; Brown, Matthew A.; McCarthy, Mark I.; Yang, Jian

    2012-01-01

    The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs). These studies were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders. We start by giving a number of quotes from scientists and journalists about perceived problems with GWASs. We will then briefly give the history of GWASs and focus on the discoveries made through this experimental design, what those discoveries tell us and do not tell us about the genetics and biology of complex traits, and what immediate utility has come out of these studies. Rather than giving an exhaustive review of all reported findings for all diseases and other complex traits, we focus on the results for auto-immune diseases and metabolic diseases. We return to the perceived failure or disappointment about GWASs in the concluding section. PMID:22243964

  10. Sea Level Rise Data Discovery

    NASA Astrophysics Data System (ADS)

    Quach, N.; Huang, T.; Boening, C.; Gill, K. M.

    2016-12-01

    Research related to sea level rise crosses multiple disciplines from sea ice to land hydrology. The NASA Sea Level Change Portal (SLCP) is a one-stop source for current sea level change information and data, including interactive tools for accessing and viewing regional data, a virtual dashboard of sea level indicators, and ongoing updates through a suite of editorial products that include content articles, graphics, videos, and animations. The architecture behind the SLCP makes it possible to integrate web content and data relevant to sea level change that are archived across various data centers as well as new data generated by sea level change principal investigators. The Extensible Data Gateway Environment (EDGE) is incorporated into the SLCP architecture to provide a unified platform for web content and science data discovery. EDGE is a data integration platform designed to facilitate high-performance geospatial data discovery and access with the ability to support multi-metadata standard specifications. EDGE has the capability to retrieve data from one or more sources and package the resulting sets into a single response to the requestor. With this unified endpoint, the Data Analysis Tool that is available on the SLCP can retrieve dataset and granule level metadata as well as perform geospatial search on the data. This talk focuses on the architecture that makes it possible to seamlessly integrate and enable discovery of disparate data relevant to sea level rise.

  11. Computational Methods in Drug Discovery

    PubMed Central

    Sliwoski, Gregory; Kothiwale, Sandeepkumar; Meiler, Jens

    2014-01-01

    Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature. PMID:24381236

  12. Optimizing Viral Discovery in Bats

    PubMed Central

    Young, Cristin C. W.; Olival, Kevin J.

    2016-01-01

    Viral discovery studies in bats have increased dramatically over the past decade, yet a rigorous synthesis of the published data is lacking. We extract and analyze data from 93 studies published between 2007–2013 to examine factors that increase success of viral discovery in bats, and specific trends and patterns of infection across host taxa and viral families. Over the study period, 248 novel viruses from 24 viral families have been described. Using generalized linear models, at a study level we show the number of host species and viral families tested best explained number of viruses detected. We demonstrate that prevalence varies significantly across viral family, specimen type, and host taxonomy, and calculate mean PCR prevalence by viral family and specimen type across all studies. Using a logistic model, we additionally identify factors most likely to increase viral detection at an individual level for the entire dataset and by viral families with sufficient sample sizes. Our analysis highlights major taxonomic gaps in recent bat viral discovery efforts and identifies ways to improve future viral pathogen detection through the design of more efficient and targeted sample collection and screening approaches. PMID:26867024

  13. A New Universe of Discoveries

    NASA Astrophysics Data System (ADS)

    Córdova, France A.

    2016-01-01

    The convergence of emerging advances in astronomical instruments, computational capabilities and talented practitioners (both professional and civilian) is creating an extraordinary new environment for making numerous fundamental discoveries in astronomy, ranging from the nature of exoplanets to understanding the evolution of solar systems and galaxies. The National Science Foundation is playing a critical role in supporting, stimulating, and shaping these advances. NSF is more than an agency of government or a funding mechanism for the infrastructure of science. The work of NSF is a sacred trust that every generation of Americans makes to those of the next generation, that we will build on the body of knowledge we inherit and continue to push forward the frontiers of science. We never lose sight of NSF's obligation to "explore the unexplored" and inspire all of humanity with the wonders of discovery. As the only Federal agency dedicated to the support of basic research and education in all fields of science and engineering, NSF has empowered discoveries across a broad spectrum of scientific inquiry for more than six decades. The result is fundamental scientific research that has had a profound impact on our nation's innovation ecosystem and kept our nation at the very forefront of the world's science-and-engineering enterprise.

  14. Object discovery, identification, and association

    NASA Astrophysics Data System (ADS)

    Kumar, Vijay; Metzler, James; Linderman, Mark; Jones, Jon; Alford, Mark; Bubalo, Adnan; Scalzo, Maria

    2011-06-01

    Tracking process captures the state of an object. The state of an object is defined in terms of its dynamic and static properties such as location, speed, color, temperature, size, etc. The set of dynamic and static properties for tracking very much depends on the agency who wants to track. For example, police needs different set of properties to tracks people than to track a vehicle than the air force. The tracking scenario also affects the selection of parameters. Tracking is done by a system referred to in this paper as "Tracker." It is a system that consists of a set of input devices such as sensors and a set of algorithms that process the data captured by these input devices. The process of tracking has three distinct steps (a) object discovery, (b) identification of discovered object, and (c) object introduction to the input devices. In this paper we focus mainly on the object discovery part with a brief discussion on introduction and identification parts. We develops a formal tracking framework (model) called "Discover, Identify, and Introduce Model (DIIM)" for building efficient tracking systems. Our approach is heuristic and uses reasoning leading to learning to develop a knowledge base for object discovery. We also develop a tracker for the Air Force system called N-CET.

  15. The discovery of the vitamins.

    PubMed

    Semba, Richard D

    2012-10-01

    The discovery of the vitamins was a major scientific achievement in our understanding of health and disease. In 1912, Casimir Funk originally coined the term "vitamine". The major period of discovery began in the early nineteenth century and ended at the mid-twentieth century. The puzzle of each vitamin was solved through the work and contributions of epidemiologists, physicians, physiologists, and chemists. Rather than a mythical story of crowning scientific breakthroughs, the reality was a slow, stepwise progress that included setbacks, contradictions, refutations, and some chicanery. Research on the vitamins that are related to major deficiency syndromes began when the germ theory of disease was dominant and dogma held that only four nutritional factors were essential: proteins, carbohydrates, fats, and minerals. Clinicians soon recognized scurvy, beriberi, rickets, pellagra, and xerophthalmia as specific vitamin deficiencies, rather than diseases due to infections or toxins. Experimental physiology with animal models played a fundamental role in nutrition research and greatly shortened the period of human suffering from vitamin deficiencies. Ultimately it was the chemists who isolated the various vitamins, deduced their chemical structure, and developed methods for synthesis of vitamins. Our understanding of the vitamins continues to evolve from the initial period of discovery.

  16. Neptune's Discovery: Le Verrier, Adams, and the Assignment of Credit

    NASA Astrophysics Data System (ADS)

    Sheehan, William

    2011-01-01

    As one of the most significant achievements of 19th century astronomy, the discovery of Neptune has been the subject of a vast literature. A large part of this literature--beginning with the period immediately after the optical discovery in Berlin--has been the obsession with assigning credit to the two men who attempted to calculate the planet's position (and initially this played out against the international rivalry between France and England). Le Verrier and Adams occupied much different positions in the Scientific Establishments of their respective countries; had markedly different personalities; and approached the investigation using different methods. A psychiatrist and historian of astronomy tries to provide some new contexts to the familiar story of the discovery of Neptune, and argues that the personalities of these two men played crucial roles in their approaches to the problem they set themselves and the way others reacted to their stimuli. Adams had features of high-functioning autism, while Le Verrier's domineering, obsessive, orderly personality--though it allowed him to be immensely productive--eventually led to serious difficulties with his peers (and an outright revolt). Though it took extraordinary smarts to calculate the position of Neptune, the discovery required social skills that these men lacked--and thus the process to discovery was more bumbling and adventitious than it might have been. The discovery of Neptune occurred at a moment when astronomy was changing from that of heroic individuals to team collaborations involving multiple experts, and remains an object lesson in the sociological aspects of scientific endeavor.

  17. The Discovery Dome: A Tool for Increasing Student Engagement

    NASA Astrophysics Data System (ADS)

    Brevik, Corinne

    2015-04-01

    The Discovery Dome is a portable full-dome theater that plays professionally-created science films. Developed by the Houston Museum of Natural Science and Rice University, this inflatable planetarium offers a state-of-the-art visual learning experience that can address many different fields of science for any grade level. It surrounds students with roaring dinosaurs, fascinating planets, and explosive storms - all immersive, engaging, and realistic. Dickinson State University has chosen to utilize its Discovery Dome to address Earth Science education at two levels. University courses across the science disciplines can use the Discovery Dome as part of their curriculum. The digital shows immerse the students in various topics ranging from astronomy to geology to weather and climate. The dome has proven to be a valuable tool for introducing new material to students as well as for reinforcing concepts previously covered in lectures or laboratory settings. The Discovery Dome also serves as an amazing science public-outreach tool. University students are trained to run the dome, and they travel with it to schools and libraries around the region. During the 2013-14 school year, our Discovery Dome visited over 30 locations. Many of the schools visited are in rural settings which offer students few opportunities to experience state-of-the-art science technology. The school kids are extremely excited when the Discovery Dome visits their community, and they will talk about the experience for many weeks. Traveling with the dome is also very valuable for the university students who get involved in the program. They become very familiar with the science content, and they gain experience working with teachers as well as the general public. They get to share their love of science, and they get to help inspire a new generation of scientists.

  18. [Neurological involvement in Wegener's granulomatosis].

    PubMed

    Asakura, Kunihiko; Muto, Tatsuro

    2013-11-01

    Abstract Wegener's granulomatosis is a rare autoimmune disease associated with granulomatous inflammation and anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis. Following the discovery of ANCA, ANCA-associated vasculitis is established as a disease entity of Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical and experimental studies have provided evidences that myeloperoxidase (MPO) and proteinase 3 (PR3), which are major antigenic targets for ANCA in neutrophils, are not only disease markers but also involved in the pathogenesis. In addition, recent studies have revealed another potential antigen for ANCA, lysosomal-associated membrane protein-2 (LAMP-2). Though nervous system manifestations of Wegener's granulomatosis are less frequent than classical manifestations in the lungs and kidneys, 20-50% of patients demonstrate neurological involvements. Peripheral nervous system involvement (in generalized Wegener's granulomatosis) is more frequent than central nervous system (CNS) involvement. Multiple mononeuropathy and multiple cranial neuropathy are the most prevalent symptoms. CNS manifestations include cerebrovascular events, pachymeningitis, seizures, and reversible posterior leukoencephalopathy syndrome. Here we discuss the pathogenic mechanism of ANCA and review the literature regarding neurological involvement in Wegener's granulomatosis.

  19. Mitigating risk in academic preclinical drug discovery.

    PubMed

    Dahlin, Jayme L; Inglese, James; Walters, Michael A

    2015-04-01

    The number of academic drug discovery centres has grown considerably in recent years, providing new opportunities to couple the curiosity-driven research culture in academia with rigorous preclinical drug discovery practices used in industry. To fully realize the potential of these opportunities, it is important that academic researchers understand the risks inherent in preclinical drug discovery, and that translational research programmes are effectively organized and supported at an institutional level. In this article, we discuss strategies to mitigate risks in several key aspects of preclinical drug discovery at academic drug discovery centres, including organization, target selection, assay design, medicinal chemistry and preclinical pharmacology.

  20. Computational Physics and Drug Discovery for Infectious Diseases

    NASA Astrophysics Data System (ADS)

    McCammon, J. Andrew

    2011-03-01

    This lecture will provide a general introduction to some of the ways that modern computational physics is contributing to the discovery of new pharmaceuticals, with special emphasis on drugs for infectious diseases. The basic sciences and computing technologies involved have advanced to the point that physics-based simulations of drug targets are now yielding truly valuable suggestions for new compounds. Supported in part by NSF, NIH, HHMI, CTBP, NBCR, and SDSC.

  1. Looking Back, Looking Forward at Halogen Bonding in Drug Discovery.

    PubMed

    Mendez, Lois; Henriquez, Gabriela; Sirimulla, Suman; Narayan, Mahesh

    2017-08-24

    Halogen bonding has emerged at the forefront of advances in improving ligand: receptor interactions. In particular the newfound ability of this extant non-covalent-bonding phenomena has revolutionized computational approaches to drug discovery while simultaneously reenergizing synthetic approaches to the field. Here we survey, via examples of classical applications involving halogen atoms in pharmaceutical compounds and their biological hosts, the unique advantages that halogen atoms offer as both Lewis acids and Lewis bases.

  2. Current Applications of Liquid Chromatography/Mass Spectrometry in Pharmaceutical Discovery After a Decade of Innovation

    NASA Astrophysics Data System (ADS)

    Ackermann, Bradley L.; Berna, Michael J.; Eckstein, James A.; Ott, Lee W.; Chaudhary, Ajai K.

    2008-07-01

    Current drug discovery involves a highly iterative process pertaining to three core disciplines: biology, chemistry, and drug disposition. For most pharmaceutical companies the path to a drug candidate comprises similar stages: target identification, biological screening, lead generation, lead optimization, and candidate selection. Over the past decade, the overall efficiency of drug discovery has been greatly improved by a single instrumental technique, liquid chromatography/mass spectrometry (LC/MS). Transformed by the commercial introduction of the atmospheric pressure ionization interface in the mid-1990s, LC/MS has expanded into almost every area of drug discovery. In many cases, drug discovery workflow has been changed owing to vastly improved efficiency. This review examines recent trends for these three core disciplines and presents seminal examples where LC/MS has altered the current approach to drug discovery.

  3. Modeling Truth Existence in Truth Discovery

    PubMed Central

    Zhi, Shi; Zhao, Bo; Tong, Wenzhu; Gao, Jing; Yu, Dian; Ji, Heng; Han, Jiawei

    2015-01-01

    When integrating information from multiple sources, it is common to encounter conflicting answers to the same question. Truth discovery is to infer the most accurate and complete integrated answers from conflicting sources. In some cases, there exist questions for which the true answers are excluded from the candidate answers provided by all sources. Without any prior knowledge, these questions, named no-truth questions, are difficult to be distinguished from the questions that have true answers, named has-truth questions. In particular, these no-truth questions degrade the precision of the answer integration system. We address such a challenge by introducing source quality, which is made up of three fine-grained measures: silent rate, false spoken rate and true spoken rate. By incorporating these three measures, we propose a probabilistic graphical model, which simultaneously infers truth as well as source quality without any a priori training involving ground truth answers. Moreover, since inferring this graphical model requires parameter tuning of the prior of truth, we propose an initialization scheme based upon a quantity named truth existence score, which synthesizes two indicators, namely, participation rate and consistency rate. Compared with existing methods, our method can effectively filter out no-truth questions, which results in more accurate source quality estimation. Consequently, our method provides more accurate and complete answers to both has-truth and no-truth questions. Experiments on three real-world datasets illustrate the notable advantage of our method over existing state-of-the-art truth discovery methods. PMID:26705507

  4. Diabetes Mellitus: Channeling Care through Cellular Discovery

    PubMed Central

    Maiese, Kenneth; Shang, Yan Chen; Chong, Zhao Zhong; Hou, Jinling

    2010-01-01

    Diabetes mellitus (DM) impacts a significant portion of the world’s population and care for this disorder places an economic burden on the gross domestic product for any particular country. Furthermore, both Type 1 and Type 2 DM are becoming increasingly prevalent and there is increased incidence of impaired glucose tolerance in the young. The complications of DM are protean and can involve multiple systems throughout the body that are susceptible to the detrimental effects of oxidative stress and apoptotic cell injury. For these reasons, innovative strategies are necessary for the implementation of new treatments for DM that are generated through the further understanding of cellular pathways that govern the pathological consequences of DM. In particular, both the precursor for the coenzyme β-nicotinamide adenine dinucleotide (NAD+), nicotinamide, and the growth factor erythropoietin offer novel platforms for drug discovery that involve cellular metabolic homeostasis and inflammatory cell control. Interestingly, these agents and their tightly associated pathways that consist of cell cycle regulation, protein kinase B, forkhead transcription factors, and Wnt signaling also function in a broader sense as biomarkers for disease onset and progression. PMID:20158461

  5. Aquaporins as targets for drug discovery.

    PubMed

    Frigeri, Antonio; Nicchia, Grazia Paola; Svelto, Maria

    2007-01-01

    The intracellular hydric balance is an essential process of mammalian cells. The water movement across cell membranes is driven by osmotic and hydrostatic forces and the speed of this process is dependent on the presence of specific aquaporin water channels. Since the molecular identification of the first water channel, AQP1, by Peter Agre's group, 13 homologous members have been found in mammals with varying degree of homology. The fundamental importance of these proteins in all living cells is suggested by their genetic conservation in eukaryotic organisms through plants to mammals. A number of recent studies have revealed the importance of mammalian AQPs in both physiology and pathophysiology and have suggested that pharmacological modulation of aquaporins expression and activity may provide new tools for the treatment of variety of human disorders, such as brain edema, glaucoma, tumour growth, congestive heart failure and obesity in which water and small solute transport may be involved. This review will highlight the physiological role and the pathological involvement of AQPs in mammals and the potential use of some recent therapeutic approaches, such as RNAi and immunotherapy, for AQP-related diseases. Furthermore, strategies that can be developed for the discovery of selective AQP-drugs will be introduced and discussed.

  6. Diabetes mellitus: channeling care through cellular discovery.

    PubMed

    Maiese, Kenneth; Shang, Yan Chen; Chong, Zhao Zhong; Hou, Jinling

    2010-02-01

    Diabetes mellitus (DM) impacts a significant portion of the world's population and care for this disorder places an economic burden on the gross domestic product for any particular country. Furthermore, both Type 1 and Type 2 DM are becoming increasingly prevalent and there is increased incidence of impaired glucose tolerance in the young. The complications of DM are protean and can involve multiple systems throughout the body that are susceptible to the detrimental effects of oxidative stress and apoptotic cell injury. For these reasons, innovative strategies are necessary for the implementation of new treatments for DM that are generated through the further understanding of cellular pathways that govern the pathological consequences of DM. In particular, both the precursor for the coenzyme beta-nicotinamide adenine dinucleotide (NAD(+)), nicotinamide, and the growth factor erythropoietin offer novel platforms for drug discovery that involve cellular metabolic homeostasis and inflammatory cell control. Interestingly, these agents and their tightly associated pathways that consist of cell cycle regulation, protein kinase B, forkhead transcription factors, and Wnt signaling also function in a broader sense as biomarkers for disease onset and progression.

  7. 17 CFR 12.30 - Methods of discovery.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false Methods of discovery. 12.30... REPARATIONS Discovery § 12.30 Methods of discovery. (a) In general. Parties may obtain discovery by the...) Admissions (§ 12.33). (b) Scope of discovery. The scope of discovery is as follows: (1) Relevancy. Except...

  8. 17 CFR 12.30 - Methods of discovery.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Methods of discovery. 12.30... REPARATIONS Discovery § 12.30 Methods of discovery. (a) In general. Parties may obtain discovery by the...) Admissions (§ 12.33). (b) Scope of discovery. The scope of discovery is as follows: (1) Relevancy. Except...

  9. 17 CFR 12.30 - Methods of discovery.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Methods of discovery. 12.30... REPARATIONS Discovery § 12.30 Methods of discovery. (a) In general. Parties may obtain discovery by the...) Admissions (§ 12.33). (b) Scope of discovery. The scope of discovery is as follows: (1) Relevancy. Except...

  10. Drug discovery for alopecia: gone today, hair tomorrow

    PubMed Central

    Santos, Zenildo; Avci, Pinar; Hamblin, Michael R

    2015-01-01

    Introduction Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. Areas covered In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-α reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8+NK group 2D-positive (NKG2D+) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. Expert opinion The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play. PMID:25662177

  11. Stabilization of protein-protein interactions in drug discovery.

    PubMed

    Andrei, Sebastian A; Sijbesma, Eline; Hann, Michael; Davis, Jeremy; O'Mahony, Gavin; Perry, Matthew W D; Karawajczyk, Anna; Eickhoff, Jan; Brunsveld, Luc; Doveston, Richard G; Milroy, Lech-Gustav; Ottmann, Christian

    2017-09-01

    PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.

  12. Drug discovery for alopecia: gone today, hair tomorrow.

    PubMed

    Santos, Zenildo; Avci, Pinar; Hamblin, Michael R

    2015-03-01

    Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-α reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8(+)NK group 2D-positive (NKG2D(+)) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play.

  13. Discovery Through the Computational Microscope

    PubMed Central

    Lee, Eric H.; Hsin, Jen; Sotomayor, Marcos; Comellas, Gemma; Schulten, Klaus

    2010-01-01

    Summary All-atom molecular dynamics simulations have become increasingly popular as a tool to investigate protein function and dynamics. However, researchers are concerned about the short time scales covered by simulations, the apparent impossibility to model large and integral biomolecular systems, and the actual predictive power of the molecular dynamics methodology. Here we review simulations that were in the past both hotly disputed and considered key successes, namely of proteins with mainly mechanical functions (titin, fibrinogen, ankyrin, and cadherin). The simulation work covered shows how state-of-the-art modeling alleviates some of the prior concerns, and how unrefuted discoveries are made through the “computational microscope". PMID:19836330

  14. Superconductivity: Anatomy of a Discovery

    NASA Astrophysics Data System (ADS)

    Pesic, Peter

    2011-04-01

    The discovery of superconductivity in 1911 by Heike Kamerlingh Onnes and his collaborators, though unexpected, rested on thirty years of prior work perfecting and applying the techniques of low temperature physics. His achievements reflected both his experimental skill and his close study of theory. The comparison with his competitors (especially James Dewar) reveals the effects of personal style, awareness of human nature, and organizational skill. That the actual first detection of superconductivity was made by a young assistant, Gilles Holst, raise deep questions of authorship, priority, and recognition.

  15. Metagenomic biomarker discovery and explanation

    PubMed Central

    2011-01-01

    This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/. PMID:21702898

  16. Novel Approaches for Glycodrug Discovery

    NASA Astrophysics Data System (ADS)

    Kondo, Hirosato

    This chapter will give you an overview of recent approaches for drug development, focusing on the function and roles of carbohydrates. Section 2 will outline the biochemical functions of polysaccharide (neutral polysaccharide, chitin and chitosan, glycosaminoglycan, and synthetic polysaccharides) and glycopolymers and the perspectives of their medicinal/medical use. Section 3 will outline recent biopharmaceutical research and development, utilizing the functions of carbohydrates. Section 4 will outline drug discovery and development of new medicines targeting carbohydrates. In addition, recent advances in carbohydrate synthesis technology, needed for development of new medicines, will also be described.

  17. Accelerated discovery of elpasolite scintillators

    SciTech Connect

    Doty, F. Patrick; Yang, Pin; Zhou, Xiaowang

    2014-12-01

    Elpasolite scintillators are a large family of halides which includes compounds reported to meet the NA22 program goals of <3% energy resolution at 662 keV1. This work investigated the potential to produce quality elpasolite compounds and alloys of useful sizes at reasonable cost, through systematic experimental and computational investigation of crystal structure and properties across the composition space. Discovery was accelerated by computational methods and models developed previously to efficiently identify cubic members of the elpasolite halides, and to evaluate stability of anion and cation exchange alloys.

  18. New vaccines: challenges of discovery.

    PubMed

    Mahmoud, Adel

    2016-09-01

    Vaccines have been a major component of preventing and controlling infectious diseases. The basis for discovery of what protects is reviewed as well as new attempts in utilizing Reverse Vaccinology, RNA-RNA methods and proteome analysis are adding significantly to our knowledge. The challenge of how to define protective and defined components of microbes is still hampering efforts to discover new vaccines. Recent excitement about immunotherapy of cancer opens the way to develop vaccines against multiple malignancies. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  19. Grid technologies empowering drug discovery.

    PubMed

    Chien, Andrew; Foster, Ian; Goddette, Dean

    2002-10-15

    Grid technologies enable flexible coupling and sharing of computers, instruments and storage. Grids can provide technical solutions to the volume of data and computational demands associated with drug discovery by delivering larger computing capability (flexible resource sharing), providing coordinated access to large data resources and enabling novel online exploration (coupling computing, data and instruments online). Here, we illustrate this potential by describing two applications: the use of desktop PC grid technologies for virtual screening, and distributed X-ray structure reconstruction and online visualization.

  20. Michaelis and Menten and the long road to the discovery of cooperativity.

    PubMed

    Cárdenas, María Luz

    2013-09-02

    This article sketches the road from the establishment of the principles of enzyme kinetics, at the beginning of the 20th century, to the discovery of regulatory mechanisms and the models to explain them, from the middle of the century onwards. A long gap in time separates the two periods, in which technological advances were made that allowed the discovery of feedback inhibition and cooperativity. In particular, these discoveries and the theory needed to explain them could not have been made without knowledge of the major metabolic pathways and the enzymes and metabolites involved in them.

  1. The changing landscape of cancer drug discovery: a challenge to the medicinal chemist of tomorrow.

    PubMed

    Pors, Klaus; Goldberg, Frederick W; Leamon, Christopher P; Rigby, Alan C; Snyder, Scott A; Falconer, Robert A

    2009-11-01

    Since the development of the first cytotoxic agents, synthetic organic chemistry has advanced enormously. The synthetic and medicinal chemists of today are at the centre of drug development and are involved in most, if not all, processes of drug discovery. Recent decreases in government funding and reformed educational policies could, however, seriously impact on drug discovery initiatives worldwide. Not only could these changes result in fewer scientific breakthroughs, but they could also negatively affect the training of our next generation of medicinal chemists.

  2. 17 CFR Appendix A to Part 36 - Guidance on Significant Price Discovery Contracts

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... significant price discovery contract traded on an electronic trading facility, to value a position, transfer..., value or otherwise offset the price-linked contract. The link may involve a one-to-one linkage, in that the value of the linked contract is based on a single contract's price, or it may involve...

  3. 17 CFR Appendix A to Part 36 - Guidance on Significant Price Discovery Contracts

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... significant price discovery contract traded on an electronic trading facility, to value a position, transfer..., value or otherwise offset the price-linked contract. The link may involve a one-to-one linkage, in that the value of the linked contract is based on a single contract's price, or it may involve...

  4. 17 CFR Appendix A to Part 36 - Guidance on Significant Price Discovery Contracts

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... significant price discovery contract traded on an electronic trading facility, to value a position, transfer..., value or otherwise offset the price-linked contract. The link may involve a one-to-one linkage, in that the value of the linked contract is based on a single contract's price, or it may involve...

  5. Carbohydrate chemistry in drug discovery.

    PubMed

    Galan, M Carmen; Benito-Alifonso, David; Watt, Gregory M

    2011-05-21

    The multitude of roles that carbohydrates and their glyco-conjugates play in biological processes has stimulated great interest in determining the nature of their interactions in both normal and diseased states. Manipulating such interactions will provide leads for drug discovery. Of the major classes of biomolecule, carbohydrates are the most structurally diverse. This hetereogeneity makes isolation of pure samples, and in sufficient amounts, from biological sources extremely difficult. Chemical synthesis offers the advantage of producing pure and structurally defined oligosaccharides for biological investigations. Although the complex nature of carbohydrates means that this is challenging, recent advances in the field have facilitated access to these molecules. The synthesis and isolation of oligosaccharides combined with progress in glycoarray technology have aided the identification of new carbohydrate-binding drug targets. This review aims to provide an overview of the latest advancements in carbohydrate chemistry and the role of these complex molecules in drug discovery, focusing particularly on synthetic methodologies, glycosaminoglycans, glycoprotein synthesis and vaccine development over the last few years.

  6. The Discovery of Artificial Radioactivity

    NASA Astrophysics Data System (ADS)

    Guerra, Francesco; Leone, Matteo; Robotti, Nadia

    2012-03-01

    We reconstruct Frédéric Joliot and Irène Curie's discovery of artificial radioactivity in January 1934 based in part on documents preserved in the Joliot-Curie Archives in Paris, France. We argue that their discovery followed from the convergence of two parallel lines of research, on the neutron and on the positron, that were focused on a well-defined experimental problem, the nuclear transmutation of aluminum and other light elements. We suggest that a key role was played by a suggestion that Francis Perrin made at the seventh Solvay Conference at the end of October 1933, that the alpha-particle bombardment of aluminum produces an intermediate unstable isotope of phosphorus, which then decays by positron emission. We also suggest that a further idea that Perrin published in December 1933, and the pioneering theory of beta decay that Enrico Fermi also first published in December 1933, established a new theoretical framework that stimulated Joliot to resume the researches that he and Curie had interrupted after the Solvay Conference, now for the first time using a Geiger-Müller counter to detect the positrons emitted when he bombarded aluminum with polonium alpha particles.

  7. Van Allen Discovery Most Important

    NASA Technical Reports Server (NTRS)

    Jastrow, R.

    1959-01-01

    The first step toward the exploration of space occurred approximately 22 months ago as a part of the International Geophysical Year. In the short interval since October, 1957, the new tools of research, the satellite and the space rocket, have produced two unexpected results of fundamental scientific importance. First, instruments placed in the Explorer satellites by James A. Van Allen have revealed the existence of layers of energetic particles in the outer atmosphere. This discovery constitutes the most significant research achievement of the IGY satellite program. The layers may provide the explanation for the aurora and other geophysical phenomena, and they will also influence the design of vehicles for manned space flight, whose occupants must be shielded against their harmful biological effects. Second, the shape of the earth has been determined very accurately with the aid of data from the first Vanguard. As a result of this investigation, we have found that our planet tends toward the shape of a pear, with its stem at the North Pole. This discovery may produce major changes in our ideas on the interior structure of the earth.

  8. Molecular Networks in Drug Discovery

    PubMed Central

    Morrow, John Kenneth; Tian, Longzhang; Zhang, Shuxing

    2013-01-01

    Despite the dramatic increase of global spending on drug discovery and development, the approval rate for new drugs is declining, due chiefly to toxicity and undesirable side effects. Simultaneously, the growth of available biomedical data in the post-genomic era has provided fresh insight into the nature of redundant and compensatory drug-target pathways. This stagnation in drug approval can be overcome by the novel concept of polypharmacology, which is built on the fundamental concept that drugs modulate multiple targets. Polypharmacology can be studied with molecular networks which integrate multidisciplinary concepts including cheminformatics, bioinformatics, and systems biology. In silico techniques such as structure and ligand-based approaches can be employed to study molecular networks and reduce costs by predicting adverse drug reactions and toxicity in the early stage of drug development. By amalgamating strides in this informatics-driven era, designing polypharmacological drugs with molecular network technology exemplifies the next generation of therapeutics with less off-target properties and toxicity. In this review, we will first describe the challenges in drug discovery, and showcase successes using multi-target drugs toward diseases such as cancer and mood disorders. We will then focus on recent development of in silico polypharmacology predictions. Finally, our technologies in molecular network analysis will be presented. PMID:20932236

  9. Metadata-Centric Discovery Service

    NASA Astrophysics Data System (ADS)

    Huang, T.; Chung, N. T.; Gangl, M. E.; Armstrong, E. M.

    2011-12-01

    It is data about data. It is the information describing a picture without looking at the picture. Through the years, the Earth Science community seeks better methods to describe science artifacts to improve the quality and efficiency in information exchange. One the purposes are to provide information to the users to guide them into identifies the science artifacts of their interest. The NASA Distributed Active Archive Centers (DAACs) are the building blocks of a data centric federation, designed for processing and archiving from NASA's Earth Observation missions and their distribution as well as provision of specialized services to users. The Physical Oceanography Distributed Active Archive Center (PO.DAAC), at the Jet Propulsion Laboratory, archives and distributes science artifacts pertain to the physical state of the ocean. As part of its high-performance operational Data Management and Archive System (DMAS) is a fast data discovery RESTful web service called the Oceanographic Common Search Interface (OCSI). The web service searches and delivers metadata on all data holdings within PO.DAAC. Currently OCSI supports metadata standards such as ISO-19115, OpenSearch, GCMD, and FGDC, with new metadata standards still being added. While we continue to seek the silver bullet in metadata standard, the Earth Science community is in fact consists of various standards due to the specific needs of its users and systems. This presentation focuses on the architecture behind OCSI as a reference implementation on building a metadata-centric discovery service.

  10. Discoveries, financial strength lift Colombia

    SciTech Connect

    Koen, A.D.

    1996-07-15

    Colombia plans to play a growing role in international oil markets while expanding and privatizing its domestic gas and electricity industries. Officials intend to curb the government`s spending on energy development while increasing its energy revenues. Their plans imply growing participation in energy projects by private companies. Also certain to help attract investment capital is the country`s new standing as a world-class oil and gas province. Discovery of Cusiana oil field in 1989 and of Cupiagua oil field in 1992 added 2 billion bbl of oil and 3 tcf of gas reserves, effectively doubling Colombia`s totals. Exploration near the giant Cusiana-Cupiagua complex, in the eastern foothills of the Andes about 100 miles northeast of Bogota, has turned up an estimated 10 tcf of gas and 1 billion bbl of oil in Volcanera field and two discoveries overlying it, Florena and Pauto Sur. Colombia`s critics say that, despite its laudable economic stability and improving oil and gas prospectivity, political impediments could interfere with progress toward its lofty energy goals. The paper discusses the heightened political risks, unequal pace of reform, gas pipeline construction, gas regulations, tying gas to power, reform in the oil sector, achieving sustainable change, and the appeal to investors.

  11. Knowledge discovery by accuracy maximization

    PubMed Central

    Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

    2014-01-01

    Here we describe KODAMA (knowledge discovery by accuracy maximization), an unsupervised and semisupervised learning algorithm that performs feature extraction from noisy and high-dimensional data. Unlike other data mining methods, the peculiarity of KODAMA is that it is driven by an integrated procedure of cross-validation of the results. The discovery of a local manifold’s topology is led by a classifier through a Monte Carlo procedure of maximization of cross-validated predictive accuracy. Briefly, our approach differs from previous methods in that it has an integrated procedure of validation of the results. In this way, the method ensures the highest robustness of the obtained solution. This robustness is demonstrated on experimental datasets of gene expression and metabolomics, where KODAMA compares favorably with other existing feature extraction methods. KODAMA is then applied to an astronomical dataset, revealing unexpected features. Interesting and not easily predictable features are also found in the analysis of the State of the Union speeches by American presidents: KODAMA reveals an abrupt linguistic transition sharply separating all post-Reagan from all pre-Reagan speeches. The transition occurs during Reagan’s presidency and not from its beginning. PMID:24706821

  12. Object Discovery via Cohesion Measurement.

    PubMed

    Guo, Guanjun; Wang, Hanzi; Zhao, Wan-Lei; Yan, Yan; Li, Xuelong

    2017-02-16

    Color and intensity are two important components in an image. Usually, groups of image pixels, which are similar in color or intensity, are an informative representation for an object. They are therefore particularly suitable for computer vision tasks, such as saliency detection and object proposal generation. However, image pixels, which share a similar real-world color, may be quite different since colors are often distorted by intensity. In this paper, we reinvestigate the affinity matrices originally used in image segmentation methods based on spectral clustering. A new affinity matrix, which is robust to color distortions, is formulated for object discovery. Moreover, a cohesion measurement (CM) for object regions is also derived based on the formulated affinity matrix. Based on the new CM, a novel object discovery method is proposed to discover objects latent in an image by utilizing the eigenvectors of the affinity matrix. Then we apply the proposed method to both saliency detection and object proposal generation. Experimental results on several evaluation benchmarks demonstrate that the proposed CM-based method has achieved promising performance for these two tasks.

  13. Discovery of novel isoforms of huntingtin reveals a new hominid-specific exon.

    PubMed

    Ruzo, Albert; Ismailoglu, Ismail; Popowski, Melissa; Haremaki, Tomomi; Croft, Gist F; Deglincerti, Alessia; Brivanlou, Ali H

    2015-01-01

    Huntington's disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC) lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease.

  14. Modeling Loss Amplification After Devastating Disasters

    NASA Astrophysics Data System (ADS)

    Boissonnade, A. C.; Muir Wood, R.

    2008-05-01

    With the catastrophic events that occurred in 2004 and 2005 came the realization that Catastrophic (Cat) loss models were not properly modeling insured losses and their associated uncertainty. One reason was that major catastrophes were generally characterized by losses caused by the primary initiating events. Such approaches are not adequate when losses can result from the compounded impacts of scenarios of secondary cascading events (physical, economic, social and political) that can have much larger impacts than those due to the primary events themselves. Situations where more and more cascading events can occur will result in different outcomes, some leading to extreme loss events, generally referred as Super Cats. These situations occurred in December 2004 with the Sumatra earthquake and tsunami and in August 2005 with hurricane Katrina and resulting New Orleans flooding. A review of historical events shows that these events are not exceptions. Modeling such scenarios adds new levels of complexity and different perspectives in the understanding of characterizing and assessing impacts of catastrophic events. Modeling economic consequences of extreme events can be improved by developing scenarios of cascades of secondary events triggered by the primary event(s). The likelihood of each scenario should be modeled, along with the hazards of primary and secondary events and resulting losses with their impacts to the different stakeholders. In addition, it is also important to model the impacts of the hazards on the infrastructure and the resulting disruption to the residents and the local economy because these can result in additional losses. This paper describes current work with the goals of better modeling the full economic impacts from catastrophic events, and of a more comprehensive treatment of uncertainty. We will present approaches for modeling loss amplification that account for all the ways in which the cost incurred for a certain level of damage due to a primary peril can be amplified. Based on an assessment of the consequences of primary and consequential or secondary perils, previously non modeled losses can be accounted for among the different stakeholders (coverage expansion). Levels of disruption, expressed in number of days of loss of function of structures, can also be estimated and then used for modeling the increase in structure and content vulnerability (deterioration vulnerability). A more comprehensive point of view of the potential total losses to be paid by different stakeholders is therefore possible, by estimating total losses across main and consequential perils. These estimates of total economic losses are also a more appropriate representation of the economic impacts of the extreme events. In turn, these allow for better modeling of the economic demand surge or inflation in repair costs as a result of the excess of demand over supply for both construction labor and materials. With such an approach it is possible to better appreciate the impact of mitigation measures. One such measure would be to reduce the impact of economic demand by making arrangements with contractors before the event. Another benefit would be increased readiness in dealing with the aftermath of such events, for example in managing claim inflation more efficiently.

  15. Devastating penile mycosis leading to penile gangrene.

    PubMed

    Hombalkar, N N; Vaze, Dhananjay; Guha, Poonam; Dhandore, Priya D; Gurav, Prakash D

    2013-09-01

    Infective penile gangrene is a rare but known complication of circumcision. The causes may vary from neutropenia, diabetes mellitus, and human immunodeficiency virus infection to lymphoproliferative malignancy. Penile mycosis leading to penile gangrene is a rare entity. Only 1 case has been reported in an adult. Juvenile diabetes mellitus is a peculiar predisposing factor for mycotic infections. We report a case of mycotic penile gangrene in a diabetic child to highlight its potentially preventable disastrous outcome.

  16. Devastating Carolina Floods Viewed by NASA SMAP

    NASA Image and Video Library

    2015-10-08

    Surface soil moisture in the Southeastern United States as retrieved from NASA's Soil Moisture Active Passive (SMAP) satellite observatory at around 6 a.m. on Oct. 5, 2015. Large parts of South Carolina appear blue, representing the impact of heavy localized rains and flooding. Regions in blue indicate areas with saturated soil conditions and possible standing water. Large-scale flooding was experienced all over South Carolina on Oct. 5-6, 2015. As of Oct. 7, 17 deaths had been attributed to these floods, with heavy economic losses. In some regions, the intensity of these floods was described as a 1,000-year storm (1-in-1,000 chance of happening in any given year). At least 14 dams have already failed as a result of these floods. http://photojournal.jpl.nasa.gov/catalog/PIA20001

  17. Gene discovery and the genetic basis of calcium consumption

    PubMed Central

    Tordoff, Michael G.

    2008-01-01

    This review makes the case that gene discovery is a worthwhile approach to the study of ingestive behavior in general and to calcium appetite in particular. A description of the methods used to discover genes is provided for non-geneticists. Areas covered include the characterization of an appropriate phenotype, the choice of suitable mouse strains, the generation of a hybrid cross, interval mapping, congenic strain production, and candidate gene analysis. The approach is illustrated with an example involving mice of the C57BL/6J and PWK/PhJ strains, which differ in avidity for calcium solutions. The variation between the strains can be attributed to at least seven quantitative trait loci (QTLs). One of these QTLs is most likely accounted for by Tas1r3, which is a gene involved in the detection of sweet and umami tastes. The discovery of a novel function for a gene with no previously known role in calcium consumption illustrates the power of gene discovery methods to uncover novel mechanisms. PMID:18499198

  18. Lupus Gastrointestinal Tract Vasculopathy: Lupus “Enteritis” Involving the Entire Gastrointestinal Tract from Esophagus to Rectum

    PubMed Central

    Bert, Joseph; Gertner, Elie

    2017-01-01

    Gastrointestinal symptoms are very common in systemic lupus erythematosus (SLE). Lupus “enteritis” is very responsive to treatment but can have devastating consequences if not detected. Most descriptions of enteritis involve the small and large bowel. This is the first report of lupus “enteritis” involving the entire gastrointestinal tract from the esophagus and stomach to the rectum. Lupus “enteritis” is another cause of upper gastrointestinal involvement in SLE (involving even the esophagus and stomach) in addition to involvement of the lower intestinal tract. PMID:28203138

  19. STS-131: Discovery Does Backflip at Station

    NASA Image and Video Library

    Commander Alan Poindexter performs a Rendezvous Pitch Maneuver as Discovery approaches the International Space Station for docking, allowing the station crew to photograph the orbiter's heat shield...

  20. STS-124 Space Shuttle Discovery Landing

    NASA Image and Video Library

    2008-06-14

    Vice President of the Japan Aerospace Exploration Agency (JAXA) Mr. Kaoru Mamiya, left, and Mr. Yuichi Yamaura of JAXA look at one of the space shuttle Discovery tires shortly after Discovery touched down at 11:15 a.m., Saturday, June 14, 2008, at the Kennedy Space Center in Cape Canaveral, Florida. During the 14-day STS-124 mission Discovery's crew installed the Japan Aerospace Exploration Agency's large Kibo laboratory and its remote manipulator system leaving a larger space station and one with increased science capabilities. Discovery also brought home NASA astronaut Garrett Reisman after his 3 month mission onboard the International Space Station. Photo Credit: (NASA/Bill Ingalls)

  1. Torpor induction in mammals: Recent discoveries fueling new ideas

    PubMed Central

    Melvin, Richard G.; Andrews, Matthew T.

    2009-01-01

    When faced with a harsh climate or inadequate food, some mammals enter a state of suspended animation known as torpor. A major goal of torpor research is to determine mechanisms that integrate environmental cues, gene expression and metabolism to produce periods of torpor lasting from hours to weeks. Recent discoveries spanning the metazoa suggest that sirtuins, the mammalian circadian clock, fibroblast growth factor 21 (FGF21) and lipids are involved in torpor induction. For example, sirtuins link cellular energy status to the mammalian circadian clock, oxidative stress, and metabolic fuel selection. In this review, we discuss how these recent discoveries form a new hypothesis linking changes in the physical environment with changes in the expression of genes that regulate torpor induction. PMID:19864159

  2. Neuroscience-driven discovery and development of sleep therapeutics.

    PubMed

    Dresler, M; Spoormaker, V I; Beitinger, P; Czisch, M; Kimura, M; Steiger, A; Holsboer, F

    2014-03-01

    Until recently, neuroscience has given sleep research and discovery of better treatments of sleep disturbances little attention, despite the fact that disturbed sleep has overwhelming impact on human health. Sleep is a complex phenomenon in which specific psychological, electrophysiological, neurochemical, endocrinological, immunological and genetic factors are involved. The brain as both the generator and main object of sleep is obviously of particular interest, which makes a neuroscience-driven view the most promising approach to evaluate clinical implications and applications of sleep research. Polysomnography as the gold standard of sleep research, complemented by brain imaging, neuroendocrine testing, genomics and other laboratory measures can help to create composite biomarkers that allow maximizing the effects of individualized therapies while minimizing adverse effects. Here we review the current state of the neuroscience of sleep, sleep disorders and sleep therapeutics and will give some leads to promote the discovery and development of sleep medicines that are better than those we have today.

  3. Torpor induction in mammals: recent discoveries fueling new ideas.

    PubMed

    Melvin, Richard G; Andrews, Matthew T

    2009-12-01

    When faced with a harsh climate or inadequate food, some mammals enter a state of suspended animation known as torpor. A major goal of torpor research is to determine mechanisms that integrate environmental cues, gene expression and metabolism to produce periods of torpor lasting from hours to weeks. Recent discoveries spanning the Metazoa suggest that sirtuins, the mammalian circadian clock, fibroblast growth factor 21 (FGF21) and lipids are involved in torpor induction. For example, sirtuins link cellular energy status to the mammalian circadian clock, oxidative stress and metabolic fuel selection. In this review, we discuss how these recent discoveries form a new hypothesis linking changes in the physical environment with changes in the expression of genes that regulate torpor induction.

  4. Biomarker Discovery in Neurodegenerative Diseases: A Proteomic Approach

    PubMed Central

    Shi, Min; Caudle, W. Michael; Zhang, Jing

    2010-01-01

    Biomarkers for neurodegenerative disorders are essential to facilitate disease diagnosis, ideally at early stages, monitor disease progression, and assess response to existing and future treatments. Application of proteomics to the human brain, cerebrospinal fluid and plasma has greatly hastened the unbiased and high-throughput searches for novel biomarkers. There are many steps critical to biomarker discovery, whether for neurodegenerative or other diseases, including sample preparation, protein/peptide separation and identification, as well as independent confirmation and validation. In this review we have summarized current proteomics technologies involved in discovery of biomarkers for neurodegenerative diseases, practical considerations and limitations of several major aspects, as well as the current status of candidate biomarkers revealed by proteomics for Alzheimer and Parkinson diseases. PMID:18938247

  5. A Revolution in Plant Metabolism: Genome-Enabled Pathway Discovery

    PubMed Central

    Kim, Jeongwoon; Buell, C. Robin

    2015-01-01

    Genome-enabled discoveries are the hallmark of 21st century biology, including major discoveries in the biosynthesis and regulation of plant metabolic pathways. Access to next generation sequencing technologies has enabled research on the biosynthesis of diverse plant metabolites, especially secondary metabolites, resulting in a broader understanding of not only the structural and regulatory genes involved in metabolite biosynthesis but also in the evolution of chemical diversity in the plant kingdom. Several paradigms that govern secondary metabolism have emerged, including that (1) gene family expansion and diversification contribute to the chemical diversity found in the plant kingdom, (2) genes encoding biochemical pathway components are frequently transcriptionally coregulated, and (3) physical clustering of nonhomologous genes that encode components of secondary metabolic pathways can occur. With an increasing knowledge base that is coupled with user-friendly and inexpensive technologies, biochemists are poised to accelerate the annotation of biochemical pathways relevant to human health, agriculture, and the environment. PMID:26224805

  6. Antimycobacterial Metabolism: Illuminating Mycobacterium tuberculosis Biology and Drug Discovery.

    PubMed

    Awasthi, Divya; Freundlich, Joel S

    2017-09-01

    Bacteria are capable of performing a number of biotransformations that may activate or deactivate xenobiotics. Recent efforts have utilized metabolomics techniques to study the fate of small-molecule antibacterials within the targeted organism. Examples involving Mycobacterium tuberculosis are reviewed and analyzed with regard to the insights they provide as to both activation and deactivation of the antibacterial. The studies, in particular, shed light on biosynthetic transformations performed by M. tuberculosis while suggesting avenues for the evolution of chemical tools, highlighting potential areas for drug discovery, and mechanisms of approved drugs. A two-pronged approach investigating the metabolism of antibacterials within both the host and bacterium is outlined and will be of value to both the chemical biology and drug discovery fields. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Towards an integrated venomics approach for accelerated conopeptide discovery.

    PubMed

    Prashanth, Jutty Rajan; Lewis, Richard J; Dutertre, Sébastien

    2012-09-15

    Conopeptides and conotoxins are small peptides produced by cone snails as a part of their predatory/defense strategies that target key ion channels and receptors in the nervous system. Some of these peptides also potently target mammalian ion channels involved in pain pathways. As a result, these venoms are a source of valuable pharmacological and therapeutic agents. The traditional approach towards conopeptide discovery relied on activity-guided fractionation, which is time consuming and resource-intensive. In this review, we discuss the advances in the fields of transcriptomics, proteomics and bioinformatics that now allow researchers to integrate these three platforms towards a more efficient discovery strategy. In this review, we also highlight the challenges associated with the wealth of data generated with this integrated approach and briefly discuss the impact these methods could have on the field of toxinology.

  8. Personalized Therapy: Tumor Antigen Discovery for Adoptive Cellular Therapy.

    PubMed

    Yee, Cassian; Lizee, Gregory A

    Adoptive cell therapy using endogenous T cells involves the ex vivo isolation and expansion of antigen-specific T cells from the peripheral blood and is uniquely suited for validating and translating antigen discovery. Endogenous T-cell therapy does not require accessible tumor as a source of infiltrating T cells and is free of regulatory and logistical constraints associated with engineering T cells. Candidate epitope peptides identified through antigen discovery may be rapidly implemented as targets in clinical trials of endogenous T-cell therapy and even incorporated as an "ad hoc" approach to personalized treatment when autologous tumor is available. Several first-in-human studies using a uniform population of antigen-specific T cells defined by phenotype and specificity have provided a means to confirm candidate antigens as potential tumor rejection antigens and to evaluate the reasons for success or failure using as a "transferrable cellular biomarker" the adoptively transferred T cells.

  9. Personal object discovery in first-person videos.

    PubMed

    Lu, Cewu; Liao, Renjie; Jia, Jiaya

    2015-12-01

    People know and care for personal objects, which can be different for individuals. Automatically discovering personal objects is thus of great practical importance. We, in this paper, pursue this task with wearable cameras based on the common sense that personal objects generally company us in various scenes. With this clue, we exploit a new object-scene distribution for robust detection. Two technical challenges involved in estimating this distribution, i.e., scene extraction and unsupervised object discovery, are tackled. For scene extraction, we learn the latent representation instead of simply selecting a few frames from the videos. In object discovery, we build an interaction model to select frame-level objects and use nonparametric Bayesian clustering. Experiments verify the usefulness of our approach.

  10. Directional Bias and Pheromone for Discovery and Coverage on Networks

    SciTech Connect

    Fink, Glenn A.; Berenhaut, Kenneth S.; Oehmen, Christopher S.

    2012-09-11

    Natural multi-agent systems often rely on “correlated random walks” (random walks that are biased toward a current heading) to distribute their agents over a space (e.g., for foraging, search, etc.). Our contribution involves creation of a new movement and pheromone model that applies the concept of heading bias in random walks to a multi-agent, digital-ants system designed for cyber-security monitoring. We examine the relative performance effects of both pheromone and heading bias on speed of discovery of a target and search-area coverage in a two-dimensional network layout. We found that heading bias was unexpectedly helpful in reducing search time and that it was more influential than pheromone for improving coverage. We conclude that while pheromone is very important for rapid discovery, heading bias can also greatly improve both performance metrics.

  11. STS-96 Launch of Discovery from Pad 39-B

    NASA Technical Reports Server (NTRS)

    1999-01-01

    The launch of Space Shuttle Discovery on mission STS-96 is reflected in the waters of Banana Creek just after sunrise. Liftoff occurred at 6:49:42 a.m. EDT. In the shadows near the bottom are silhouetted a number of spectators at the Banana Creek viewing site. STS-96 is on a 10-day logistics and resupply mission for the International Space Station. Along with such payloads as a Russian crane, the Strela; a U.S.-built crane; the Spacehab Oceaneering Space System Box (SHOSS), a logistics items carrier; and STARSHINE, a student-involved experiment, Discovery carries about 4,000 pounds of supplies, to be stored aboard the station for use by future crews, including laptop computers, cameras, tools, spare parts, and clothing. The mission includes a space walk to attach the cranes to the outside of the ISS for use in future construction. Landing is expected at the SLF on June 6 about

  12. Serendipitous discovery of novel bacterial methionine aminopeptidase inhibitors.

    PubMed

    Evdokimov, Artem G; Pokross, Matthew; Walter, Richard L; Mekel, Marlene; Barnett, Bobby L; Amburgey, Jack; Seibel, William L; Soper, Shari J; Djung, Jane F; Fairweather, Neil; Diven, Conrad; Rastogi, Vinit; Grinius, Leo; Klanke, Charles; Siehnel, Richard; Twinem, Tracy; Andrews, Ryan; Curnow, Alan

    2007-02-15

    In this article we describe the application of structural biology methods to the discovery of novel potent inhibitors of methionine aminopeptidases. These enzymes are employed by the cells to cleave the N-terminal methionine from nascent peptides and proteins. As this is one of the critical steps in protein maturation, it is very likely that inhibitors of these enzymes may prove useful as novel antibacterial agents. Involvement of crystallography at the very early stages of the inhibitor design process resulted in serendipitous discovery of a new inhibitor class, the pyrazole-diamines. Atomic-resolution structures of several inhibitors bound to the enzyme illuminate a new mode of inhibitor binding. 2006 Wiley-Liss, Inc.

  13. Drug Discovery from Marine Microbes

    PubMed Central

    Gerwick, William H.; Fenner, Amanda M.

    2013-01-01

    The marine environment has been a source of more than 20,000 inspirational natural products discovered over the past 50 years. From these efforts, 9 approved drugs and 12 current clinical trial agents have been discovered, either as natural products or molecules inspired from the natural product structure. To a significant degree, these have come from collections of marine invertebrates largely obtained from shallow water tropical ecosystems. However, there is a growing recognition that marine invertebrates are oftentimes populated with enormous quantities of ‘associated’ or symbiotic microorganisms, and that microorganisms are the true metabolic sources of these most valuable of marine natural products. Also, because of the inherently multidisciplinary nature of this field, a high degree of innovation is characteristic of marine natural product drug discovery efforts. PMID:23274881

  14. High-throughput discovery metabolomics.

    PubMed

    Fuhrer, Tobias; Zamboni, Nicola

    2015-02-01

    Non-targeted metabolomics by mass spectrometry has established as the method of choice for investigating metabolic phenotypes in basic and applied research. Compared to other omics, metabolomics provides broad scope and yet direct information on the integrated cellular response with low demand in material and sample preparation. These features render non-targeted metabolomics ideally suited for large scale screens and discovery. Here we review the achievements and potential in high-throughput, non-targeted metabolomics. We found that routine and precise analysis of thousands of small molecular features in thousands of complex samples per day and instrument is already reality, and ongoing developments in microfluidics and integrated interfaces will likely further boost throughput in the next few years. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. New approaches to antibiotic discovery.

    PubMed

    Kealey, C; Creaven, C A; Murphy, C D; Brady, C B

    2017-03-08

    New antibiotics are urgently required by human medicine as pathogens emerge with developed resistance to almost all antibiotic classes. Pioneering approaches, methodologies and technologies have facilitated a new era in antimicrobial discovery. Innovative culturing techniques such as iChip and co-culturing methods which use 'helper' strains to produce bioactive molecules have had notable success. Exploiting antibiotic resistance to identify antibacterial producers performed in tandem with diagnostic PCR based identification approaches has identified novel candidates. Employing powerful metagenomic mining and metabolomic tools has identified the antibiotic'ome, highlighting new antibiotics from underexplored environments and silent gene clusters enabling researchers to mine for scaffolds with both a novel mechanism of action and also few clinically established resistance determinants. Modern biotechnological approaches are delivering but will require support from government initiatives together with changes in regulation to pave the way for valuable, efficacious, highly targeted, pathogen specific antimicrobial therapies.

  16. STS-131 Discovery after Undocking

    NASA Image and Video Library

    2010-04-17

    ISS023-E-025405 (17 April 2010) --- The underside of space shuttle Discovery is visible in this image photographed by an Expedition 23 crew member on the International Space Station soon after the shuttle and station began their post-undocking relative separation. Undocking of the two spacecraft occurred at 7:52 a.m. (CDT) on April 17, 2010, ending a stay of 10 days, 5 hours and 8 minutes. The visit included three spacewalks and delivery of more than seven tons of equipment and supplies. The recognizable feature on Earth below is the south end of Isla de Providencia, about 150 miles off the coast of Nicaragua near 13.3 degrees north latitude 81.4 degrees west longitude. The island belongs to Colombia.

  17. Collaborative Workspaces to Accelerate Discovery

    NASA Astrophysics Data System (ADS)

    Meade, Bernard; Fluke, Christopher; Cooke, Jeff; Andreoni, Igor; Pritchard, Tyler; Curtin, Christopher; Bernard, Stephanie R.; Asher, Albany; Mack, Katherine J.; Murphy, Michael T.; Vohl, Dany; Codoreanu, Alex; Kotuš, Srđan M.; Rumokoy, Fanuel; Horst, Chuck; Reynolds, Tristan

    2017-05-01

    By applying a display ecology to the Deeper, Wider, Faster proactive, simultaneous telescope observing campaign, we have shown a dramatic reduction in the time taken to inspect DECam CCD images for potential transient candidates and to produce time-critical triggers to standby telescopes. We also show how facilitating rapid corroboration of potential candidates and the exclusion of non-candidates improves the accuracy of detection; and establish that a practical and enjoyable workspace can improve the experience of an otherwise taxing task for astronomers. We provide a critical road test of two advanced displays in a research context-a rare opportunity to demonstrate how they can be used rather than simply discuss how they might be used to accelerate discovery.

  18. Automated Knowledge Discovery from Simulators

    NASA Technical Reports Server (NTRS)

    Burl, Michael C.; DeCoste, D.; Enke, B. L.; Mazzoni, D.; Merline, W. J.; Scharenbroich, L.

    2006-01-01

    In this paper, we explore one aspect of knowledge discovery from simulators, the landscape characterization problem, where the aim is to identify regions in the input/ parameter/model space that lead to a particular output behavior. Large-scale numerical simulators are in widespread use by scientists and engineers across a range of government agencies, academia, and industry; in many cases, simulators provide the only means to examine processes that are infeasible or impossible to study otherwise. However, the cost of simulation studies can be quite high, both in terms of the time and computational resources required to conduct the trials and the manpower needed to sift through the resulting output. Thus, there is strong motivation to develop automated methods that enable more efficient knowledge extraction.

  19. Cancer biomarker discovery and validation

    PubMed Central

    Goossens, Nicolas; Nakagawa, Shigeki; Sun, Xiaochen; Hoshida, Yujin

    2015-01-01

    With the emergence of genomic profiling technologies and selective molecular targeted therapies, biomarkers play an increasingly important role in the clinical management of cancer patients. Single gene/protein or multi-gene “signature”-based assays have been introduced to measure specific molecular pathway deregulations that guide therapeutic decision-making as predictive biomarkers. Genome-based prognostic biomarkers are also available for several cancer types for potential incorporation into clinical prognostic staging systems or practice guidelines. However, there is still a large gap between initial biomarker discovery studies and their clinical translation due to the challenges in the process of cancer biomarker development. In this review we summarize the steps of biomarker development, highlight key issues in successful validation and implementation, and overview representative examples in the oncology field. We also discuss regulatory issues and future perspectives in the era of big data analysis and precision medicine. PMID:26213686

  20. Biomedical Application of Knowledge Discovery

    NASA Astrophysics Data System (ADS)

    Koike, A.

    With rapid progress in biomedical fields, the knowledge accumulated in scientific papers has increased significantly. Most of these papers draw only a fragmental conclusion from the viewpoint of scientific facts, so discovery of hidden knowledge or hypothesis generation by leveraging this fragmental information has come into the limelight and more expectations on the system constructions to assist them has been paid. To respond to these expectations, we have developed a system called BioTermNet (http://btn.ontology.ims.u-tokyo.ac.jp:8081/) to make a conceptual network by connecting conceptual relationships (fragmental information) explicitly described in papers and explore the hidden relationships in the conceptual network. The conceptual relationships are extracted by hybrid methods of information extraction and information-retrieval techniques. This system has a potential for wide application. After the validation of system performance, we take up some topics of conceptual network-based analysis and refer to other applications in the future prospects section.

  1. Advancing drug discovery for schizophrenia

    PubMed Central

    Marder, Stephen R.; Roth, Bryan; Sullivan, Patrick F.; Scolnick, Edward M.; Nestler, Eric J.; Geyer, Mark A.; Welnberger, Daniel R.; Karayiorgou, Maria; Guidotti, Alessandro; Gingrich, Jay; Akbarian, Schahram; Buchanan, Robert W.; Lieberman, Jeffrey A.; Conn, P. Jeffrey; Haggarty, Stephen J.; Law, Amanda J.; Campbell, Brian; Krystal, John H.; Moghaddam, Bita; Saw, Akira; Caron, Marc G.; George, Susan R.; Allen, John A.; Solis, Michelle

    2013-01-01

    Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, “Advancing Drug Discovery for Schizophrenia” was held March 9–11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia. PMID:22032400

  2. Automated Knowledge Discovery from Simulators

    NASA Technical Reports Server (NTRS)

    Burl, Michael C.; DeCoste, D.; Enke, B. L.; Mazzoni, D.; Merline, W. J.; Scharenbroich, L.

    2006-01-01

    In this paper, we explore one aspect of knowledge discovery from simulators, the landscape characterization problem, where the aim is to identify regions in the input/ parameter/model space that lead to a particular output behavior. Large-scale numerical simulators are in widespread use by scientists and engineers across a range of government agencies, academia, and industry; in many cases, simulators provide the only means to examine processes that are infeasible or impossible to study otherwise. However, the cost of simulation studies can be quite high, both in terms of the time and computational resources required to conduct the trials and the manpower needed to sift through the resulting output. Thus, there is strong motivation to develop automated methods that enable more efficient knowledge extraction.

  3. DPS Discovery Slide Sets for the Introductory Astronomy Instructor

    NASA Astrophysics Data System (ADS)

    Meinke, Bonnie K.; Jackson, Brian; Buxner, Sanlyn; Horst, Sarah; Brain, David; Schneider, Nicholas M.

    2016-10-01

    The DPS actively supports the E/PO needs of the society's membership, including those at the front of the college classroom. The DPS Discovery Slide Sets are an opportunity for instructors to put the latest planetary science into their lectures and for scientists to get their exciting results to college students.In an effort to keep the astronomy classroom apprised of the fast moving field of planetary science, the Division for Planetary Sciences (DPS) has developed "DPS Discoveries", which are 3-slide presentations that can be incorporated into college lectures. The slide sets are targeted at the Introductory Astronomy undergraduate level. Each slide set consists of three slides which cover a description of the discovery, a discussion of the underlying science, and a presentation of the big picture implications of the discovery, with a fourth slide that includes links to associated press releases, images, and primary sources. Topics span all subdisciplines of planetary science, and 26 sets are available in Farsi and Spanish. We intend for these slide sets to help Astronomy 101 instructors include new developments (not yet in their textbooks) into the broader context of the course. If you need supplemental material for your classroom, please checkout the archived collection: http://dps.aas.org/education/dpsdiscMore slide sets are now in development and will be available soon! In the meantime, we seek input, feedback, and help from the DPS membership to add fresh slide sets to the series and to connect the college classroom to YOUR science. It's easy to get involved - we'll provide a content template, tips and tricks for a great slide set, and pedagogy reviews. Talk to a coauthor to find out how you can disseminate your science or get involved in E/PO with your contributions.

  4. A Tale of Two Discoveries: Comparing the Usability of Summon and EBSCO Discovery Service

    ERIC Educational Resources Information Center

    Foster, Anita K.; MacDonald, Jean B.

    2013-01-01

    Web-scale discovery systems are gaining momentum among academic libraries as libraries seek a means to provide their users with a one-stop searching experience. Illinois State University's Milner Library found itself in the unique position of having access to two distinct discovery products, EBSCO Discovery Service and Serials Solutions' Summon.…

  5. A Tale of Two Discoveries: Comparing the Usability of Summon and EBSCO Discovery Service

    ERIC Educational Resources Information Center

    Foster, Anita K.; MacDonald, Jean B.

    2013-01-01

    Web-scale discovery systems are gaining momentum among academic libraries as libraries seek a means to provide their users with a one-stop searching experience. Illinois State University's Milner Library found itself in the unique position of having access to two distinct discovery products, EBSCO Discovery Service and Serials Solutions' Summon.…

  6. Predicting discovery rates of genomic features.

    PubMed

    Gravel, Simon

    2014-06-01

    Successful sequencing experiments require judicious sample selection. However, this selection must often be performed on the basis of limited preliminary data. Predicting the statistical properties of the final sample based on preliminary data can be challenging, because numerous uncertain model assumptions may be involved. Here, we ask whether we can predict "omics" variation across many samples by sequencing only a fraction of them. In the infinite-genome limit, we find that a pilot study sequencing 5% of a population is sufficient to predict the number of genetic variants in the entire population within 6% of the correct value, using an estimator agnostic to demography, selection, or population structure. To reach similar accuracy in a finite genome with millions of polymorphisms, the pilot study would require ∼15% of the population. We present computationally efficient jackknife and linear programming methods that exhibit substantially less bias than the state of the art when applied to simulated data and subsampled 1000 Genomes Project data. Extrapolating based on the National Heart, Lung, and Blood Institute Exome Sequencing Project data, we predict that 7.2% of sites in the capture region would be variable in a sample of 50,000 African Americans and 8.8% in a European sample of equal size. Finally, we show how the linear programming method can also predict discovery rates of various genomic features, such as the number of transcription factor binding sites across different cell types.

  7. The ubiquitin system, disease, and drug discovery

    PubMed Central

    Petroski, Matthew D

    2008-01-01

    The ubiquitin system of protein modification has emerged as a crucial mechanism involved in the regulation of a wide array of cellular processes. As our knowledge of the pathways in this system has grown, so have the ties between the protein ubiquitin and human disease. The power of the ubiquitin system for therapeutic benefit blossomed with the approval of the proteasome inhibitor Velcade in 2003 by the FDA. Current drug discovery activities in the ubiquitin system seek to (i) expand the development of new proteasome inhibitors with distinct mechanisms of action and improved bioavailability, and (ii) validate new targets. This review summarizes our current understanding of the role of the ubiquitin system in various human diseases ranging from cancer, viral infection and neurodegenerative disorders to muscle wasting, diabetes and inflammation. I provide an introduction to the ubiquitin system, highlight some emerging relationships between the ubiquitin system and disease, and discuss current and future efforts to harness aspects of this potentially powerful system for improving human health. Republished from Current BioData's Targeted Proteins database (TPdb; ). PMID:19007437

  8. The Higgs Boson Search and Discovery

    NASA Astrophysics Data System (ADS)

    Bernardi, Gregorio; Konigsberg, Jacobo

    2016-10-01

    We present a brief account of the search for the Higgs boson at the three major colliders that have operated over the last three decades: LEP, the Tevatron, and the LHC. The experimental challenges encountered stemmed from the distinct event phenomenology as determined by the colliders energy and the possible values for the Higgs boson mass, and from the capability of these colliders to deliver as much collision data as possible to fully explore the mass spectrum within their reach. Focusing more on the hadron collider searches during the last decade, we discuss how the search for the Higgs boson was advanced through mastering the experimental signatures of standard theory backgrounds, through the comprehensive utilization of the features of the detectors involved in the searches, and by means of advanced data analysis techniques. The search culminated in 2012 with the discovery, by the ATLAS and CMS collaborations, of a Higgs-like particle with mass close to 125 GeV, confirmed more recently to have properties consistent with those expected from the standard theory Higgs boson.

  9. Cancer genomics: technology, discovery, and translation.

    PubMed

    Tran, Ben; Dancey, Janet E; Kamel-Reid, Suzanne; McPherson, John D; Bedard, Philippe L; Brown, Andrew M K; Zhang, Tong; Shaw, Patricia; Onetto, Nicole; Stein, Lincoln; Hudson, Thomas J; Neel, Benjamin G; Siu, Lillian L

    2012-02-20

    In recent years, the increasing awareness that somatic mutations and other genetic aberrations drive human malignancies has led us within reach of personalized cancer medicine (PCM). The implementation of PCM is based on the following premises: genetic aberrations exist in human malignancies; a subset of these aberrations drive oncogenesis and tumor biology; these aberrations are actionable (defined as having the potential to affect management recommendations based on diagnostic, prognostic, and/or predictive implications); and there are highly specific anticancer agents available that effectively modulate these targets. This article highlights the technology underlying cancer genomics and examines the early results of genome sequencing and the challenges met in the discovery of new genetic aberrations. Finally, drawing from experiences gained in a feasibility study of somatic mutation genotyping and targeted exome sequencing led by Princess Margaret Hospital-University Health Network and the Ontario Institute for Cancer Research, the processes, challenges, and issues involved in the translation of cancer genomics to the clinic are discussed.

  10. Algorithms for Discovery of Multiple Markov Boundaries

    PubMed Central

    Statnikov, Alexander; Lytkin, Nikita I.; Lemeire, Jan; Aliferis, Constantin F.

    2013-01-01

    Algorithms for Markov boundary discovery from data constitute an important recent development in machine learning, primarily because they offer a principled solution to the variable/feature selection problem and give insight on local causal structure. Over the last decade many sound algorithms have been proposed to identify a single Markov boundary of the response variable. Even though faithful distributions and, more broadly, distributions that satisfy the intersection property always have a single Markov boundary, other distributions/data sets may have multiple Markov boundaries of the response variable. The latter distributions/data sets are common in practical data-analytic applications, and there are several reasons why it is important to induce multiple Markov boundaries from such data. However, there are currently no sound and efficient algorithms that can accomplish this task. This paper describes a family of algorithms TIE* that can discover all Markov boundaries in a distribution. The broad applicability as well as efficiency of the new algorithmic family is demonstrated in an extensive benchmarking study that involved comparison with 26 state-of-the-art algorithms/variants in 15 data sets from a diversity of application domains. PMID:25285052

  11. Early discovery drug screening using mass spectrometry.

    PubMed

    Siegel, Marshall M

    2002-01-01

    Electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometric methods useful for early discovery drug screening are reviewed. All methods described involve studies of non-covalent complexes between biopolymer receptors and small molecule ligands formed in the condensed phase. The complexes can be sprayed intact directly into the gas phase by ESI-MS using gentle experimental conditions. Gas phase screening applications are illustrated for drug ligand candidates non-covalently interacting with peptides, proteins, RNA, and DNA. In the condensed phase, the complexes can be also isolated, denatured and analyzed by ESI-MS to identify the small molecule ligands. Condensed phase drug screening examples are illustrated for the ESI-MS ancillary techniques of affinity chromatography, ultrafiltration, ultracentrifugation, gel permeation chromatography (GPC), reverse phase-high performance liquid chromatography (RP-HPLC) and capillary electrophoretic methods. Solid phase drug screening using MALDI-MS is illustrated for small molecule ligands bound to MALDI affinity probe tips and to beads. Since ESI and MALDI principally produce molecular ions, high throughput screening is achieved by analyzing mass indexed mixtures.

  12. Limitless in a Field of Endless Discovery

    NASA Astrophysics Data System (ADS)

    Osborne, T. C.

    2014-12-01

    As students and early career scientists in today's world, we can expand our opportunities to develop skills in more than one chosen discipline. By remaining open to new experiences and challenging ourselves in new ways, we become better able to tackle today's issues. My experience with several research and field campaigns has allowed me to strengthen my proficiency and become immersed in various fields of study. Most recently, I applied stereo photogrammetric processes during the DEEPWAVE mission, which focused on deeply propagating atmospheric gravity wave dynamics upstream of the New Zealand Southern Alps. This field campaign, which took place in and around New Zealand between May 24th and July 27th, 2014, was based at Christchurch Airport, but used information from various ground-based research facilities. Two research aircraft equipped with instruments for airborne remote sensing were also involved; the NSF/NCAR HIAPER GV and the DLR Falcon. DEEPWAVE allowed for the intertwining of multiple fields of study and emphasizes the importance of an interdisciplinary approach to research. This talk explores the advantages of building more interdisciplinary and multidisciplinary skills in order to adapt to constant changes in the environment and in society. By doing so, we can remain limitless in a field of endless discovery!

  13. Discovery of Novel Haloalkane Dehalogenase Inhibitors

    PubMed Central

    Buryska, Tomas; Daniel, Lukas; Kunka, Antonin; Brezovsky, Jan; Damborsky, Jiri

    2016-01-01

    Haloalkane dehalogenases (HLDs) have recently been discovered in a number of bacteria, including symbionts and pathogens of both plants and humans. However, the biological roles of HLDs in these organisms are unclear. The development of efficient HLD inhibitors serving as molecular probes to explore their function would represent an important step toward a better understanding of these interesting enzymes. Here we report the identification of inhibitors for this enzyme family using two different approaches. The first builds on the structures of the enzymes' known substrates and led to the discovery of less potent nonspecific HLD inhibitors. The second approach involved the virtual screening of 150,000 potential inhibitors against the crystal structure of an HLD from the human pathogen Mycobacterium tuberculosis H37Rv. The best inhibitor exhibited high specificity for the target structure, with an inhibition constant of 3 μM and a molecular architecture that clearly differs from those of all known HLD substrates. The new inhibitors will be used to study the natural functions of HLDs in bacteria, to probe their mechanisms, and to achieve their stabilization. PMID:26773086

  14. Review of Existing Wormhole Attack Discovery Techniques

    DTIC Science & Technology

    2006-08-01

    Review of Existing Wormhole Attack Discovery Techniques Maria Alexandrovna Gorlatova The scientific or...DATES COVERED - 4. TITLE AND SUBTITLE Review of Existing Wormhole Attack Discovery Techniques 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Review of Existing Wormhole Attack

  15. 42 CFR 405.1037 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Discovery. 405.1037 Section 405.1037 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM FEDERAL... § 405.1016 is tolled until the discovery dispute is resolved. ...

  16. TOXICOGENOMICS DRUG DISCOVERY AND THE PATHOLOGIST

    EPA Science Inventory

    Toxicogenomics, drug discovery, and pathologist.

    The field of toxicogenomics, which currently focuses on the application of large-scale differential gene expression (DGE) data to toxicology, is starting to influence drug discovery and development in the pharmaceutical indu...

  17. 10 CFR 590.305 - Informal discovery.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Informal discovery. 590.305 Section 590.305 Energy DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Procedures § 590.305 Informal discovery. The...

  18. 10 CFR 590.305 - Informal discovery.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Informal discovery. 590.305 Section 590.305 Energy DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Procedures § 590.305 Informal discovery. The...

  19. 10 CFR 590.305 - Informal discovery.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Informal discovery. 590.305 Section 590.305 Energy DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Procedures § 590.305 Informal discovery. The...

  20. 10 CFR 590.305 - Informal discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Informal discovery. 590.305 Section 590.305 Energy DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Procedures § 590.305 Informal discovery. The...