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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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. 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).

  5. 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.

  6. 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

  7. 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.

  8. 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.

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

    PubMed

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

    2016-01-01

    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.

  10. 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.…

  11. 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.

  12. 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…

  13. 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

  14. 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

  15. [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

  16. 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

  17. 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.

  18. 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…

  19. 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

  20. 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…

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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)

  1. 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.

  2. 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; 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. 

  3. 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.

  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. 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.

  6. 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.

  7. The effect of surface cover and soil devastation on infiltration rate in steep forest plantations

    NASA Astrophysics Data System (ADS)

    Onda, Y.; Hiraoka, M.; Kato, H.; Gomi, T.; Miyata, S.; Mizugaki, S.

    2008-12-01

    The Japanese cypress (Hinoki; Chamaecyparis obtusa) is a major commercial tree species in Japan, and without thinning of high-density stands, canopy closure prevents development of understory vegetation. Therefore there is a concern for overlandflow and sediment yield due to infiltration rate lowering. We developed a light-weight rainfall simulator based on the design of Meyer and Harmon (1979). A flat fan Veejet 80150 spraying nozzle (Spraying systems Co., USA) is mounted on the manifold at 2.13 m high from the plot surface. The nozzle oscillates so that the spray fan sweeps across the targeting 1 m x 1 m plot. The Veejet 80150 spraying nozzle produces large raindrops larger than 2 mm in diameter, and can simulate the high raindrop kinetic energy of natural throughfall. A targeted rainfall rate is 180 mm/h. About 30 sprinkling experiments have been conducted on 35-degree hillslopes with varying surface cover in 5 locations in Japan. We obtained the minimum infiltration rate of 14 mm/h where the surface cover is very little. The infiltration rates were plotted against the total understory vegetation and dry weight of total surface cover including litter. The infiltration rate increased with the increasing total surface cover, and generally higher regression coefficient was found for the case of the total surface cover. In some cases, high infiltration rates were obtained where surface cover is low. Two possible explanations can be made; 1) surface soil (especially fine particles) has been washed away, where soil is mostly composed of gravel and the percentage of fine fraction is low, or 2) because of long-term soil loss by raindrop detachment, remaining soil looks like "ghanging"h between exposed fine root networks of Japanese cypress, where soil bulk density is significantly lower than other site. Therefore the infiltration rate in the devastated Japanese cypress plantations is not only controlled by loss of surface vegetation by low light condition, but soil

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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)

  18. 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.

  19. Collaboration for rare disease drug discovery research.

    PubMed

    Litterman, Nadia K; Rhee, Michele; Swinney, David C; Ekins, Sean

    2014-01-01

    Rare disease research has reached a tipping point, with the confluence of scientific and technologic developments that if appropriately harnessed, could lead to key breakthroughs and treatments for this set of devastating disorders. Industry-wide trends have revealed that the traditional drug discovery research and development (R&D) model is no longer viable, and drug companies are evolving their approach. Rather than only pursue blockbuster therapeutics for heterogeneous, common diseases, drug companies have increasingly begun to shift their focus to rare diseases. In academia, advances in genetics analyses and disease mechanisms have allowed scientific understanding to mature, but the lack of funding and translational capability severely limits the rare disease research that leads to clinical trials. Simultaneously, there is a movement towards increased research collaboration, more data sharing, and heightened engagement and active involvement by patients, advocates, and foundations. The growth in networks and social networking tools presents an opportunity to help reach other patients but also find researchers and build collaborations. The growth of collaborative software that can enable researchers to share their data could also enable rare disease patients and foundations to manage their portfolio of funded projects for developing new therapeutics and suggest drug repurposing opportunities. Still there are many thousands of diseases without treatments and with only fragmented research efforts. We will describe some recent progress in several rare diseases used as examples and propose how collaborations could be facilitated. We propose that the development of a center of excellence that integrates and shares informatics resources for rare diseases sponsored by all of the stakeholders would help foster these initiatives.

  20. Collaboration for rare disease drug discovery research

    PubMed Central

    Litterman, Nadia K.; Rhee, Michele; Swinney, David C.; Ekins, Sean

    2014-01-01

    Rare disease research has reached a tipping point, with the confluence of scientific and technologic developments that if appropriately harnessed, could lead to key breakthroughs and treatments for this set of devastating disorders. Industry-wide trends have revealed that the traditional drug discovery research and development (R&D) model is no longer viable, and drug companies are evolving their approach. Rather than only pursue blockbuster therapeutics for heterogeneous, common diseases, drug companies have increasingly begun to shift their focus to rare diseases. In academia, advances in genetics analyses and disease mechanisms have allowed scientific understanding to mature, but the lack of funding and translational capability severely limits the rare disease research that leads to clinical trials. Simultaneously, there is a movement towards increased research collaboration, more data sharing, and heightened engagement and active involvement by patients, advocates, and foundations. The growth in networks and social networking tools presents an opportunity to help reach other patients but also find researchers and build collaborations. The growth of collaborative software that can enable researchers to share their data could also enable rare disease patients and foundations to manage their portfolio of funded projects for developing new therapeutics and suggest drug repurposing opportunities. Still there are many thousands of diseases without treatments and with only fragmented research efforts. We will describe some recent progress in several rare diseases used as examples and propose how collaborations could be facilitated. We propose that the development of a center of excellence that integrates and shares informatics resources for rare diseases sponsored by all of the stakeholders would help foster these initiatives. PMID:25685324

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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…

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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…

  16. 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)…

  17. 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.

  18. [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

  19. 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.

  20. 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.

  1. 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

  2. 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)

  3. 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…

  4. 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.

  5. "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…

  6. 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.

  7. 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.

  8. 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.

  9. 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)

  10. Discovery Touches Down!

    NASA Video Gallery

    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...

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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...

  16. 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…

  17. 16 CFR 1025.31 - General provisions governing discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... not more than the maximum specified in 5 U.S.C. 3109 for the time spent in responding to discovery. (d... the Commission's statutory authority and is relevant to the subject matter involved in the proceedings, whether it relates to the claim or defense of the party seeking discovery or to the claim or defense...

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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…

  5. 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)

  6. 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,…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  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. 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…

  13. 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…

  14. 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

  15. [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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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…

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. Research Discoveries After Kubin.

    PubMed

    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?

  8. 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

  9. 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

  10. 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

    2013-01-01

    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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Hubble: 20 Years of Discovery

    NASA Video Gallery

    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 ...

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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…

  5. 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…

  6. 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…

  7. 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)

  8. 19 CFR 207.109 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Committee Proceedings § 207.109 Discovery. (a) Discovery methods. All parties may obtain discovery under such terms and limitations as the administrative law judge may order. Discovery may be by one or... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 207.109 Section 207.109 Customs...

  9. 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...

  10. 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.

  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. 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.

  13. 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

  14. 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.

  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. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Discovery Performs Terminal Initiation Burn

    NASA Video Gallery

    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 ...

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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)

  2. 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…

  3. 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)

  4. 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.

  5. 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…

  6. 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…

  7. 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...

  8. 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...

  9. 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...

  10. 15 CFR 719.10 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Discovery. 719.10 Section 719.10... Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter... the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with...

  11. 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...

  12. 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....

  13. 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...

  14. 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...

  15. 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...

  16. 15 CFR 719.10 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Discovery. 719.10 Section 719.10... Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter... the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with...

  17. 49 CFR 1503.633 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... determines appropriate. (h) Confidential orders. A party or person who has received a discovery request for... 49 Transportation 9 2014-10-01 2014-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery....

  18. 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....

  19. 29 CFR 2700.56 - Discovery; general.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Hearings § 2700.56 Discovery; general. (a) Discovery methods. Parties may obtain discovery by one or more of the following methods: Depositions upon oral examination or written questions; written... 29 Labor 9 2010-07-01 2010-07-01 false Discovery; general. 2700.56 Section 2700.56...

  20. 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...

  1. 36 CFR 1150.63 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Discovery. 1150.63 Section... PRACTICE AND PROCEDURES FOR COMPLIANCE HEARINGS Prehearing Conferences and Discovery § 1150.63 Discovery. (a) Parties are encouraged to engage in voluntary discovery procedures. For good cause shown...

  2. 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)...

  3. 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...

  4. 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...

  5. 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...

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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?

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. [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.

  7. 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…

  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. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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.

  14. 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.

  15. 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…

  16. 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.

  17. 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)

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  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. [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.

  5. 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.

  6. 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.

  7. 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)...

  8. 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

  9. 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...

  10. 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...

  11. 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...

  12. 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....

  13. 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....

  14. 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...

  15. 14 CFR 13.220 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... scope of discovery requested by the party is unduly burdensome or expensive. (g) Confidential orders. A... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery....

  16. 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...

  17. 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;...

  18. 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...

  19. 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,...

  20. 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,...

  1. 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,...

  2. 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…

  3. 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...

  4. 49 CFR 1503.633 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... any time after a complaint has been filed in the proceedings. (b) Methods of discovery. The following methods of discovery are permitted under this section: depositions on oral examination or written... the information has had ample opportunity to obtain the information through other discovery...

  5. 39 CFR 955.15 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., and those orders may include limitations on the scope, method, time and place for discovery, and... the frequency or extent of use of discovery methods described in these rules. In doing so, generally... 39 Postal Service 1 2010-07-01 2010-07-01 false Discovery. 955.15 Section 955.15 Postal...

  6. 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...

  7. 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...

  8. 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…

  9. 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...

  10. 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...

  11. 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...

  12. 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....

  13. 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....

  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. 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...

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Neurodevelopmental Animal Models of Schizophrenia: Role in Novel Drug Discovery and Development

    PubMed Central

    Wilson, Christina; Terry, Alvin V.

    2015-01-01

    Schizophrenia is a devastating mental illness that is associated with a lifetime of disability. For patients to successfully function in society, the amelioration of disease symptoms is imperative. The recently published results of two large antipsychotic clinical trials (e.g., CATIE, CUtLASS) clearly exemplified the limitations of currently available treatment options for schizophrenia, and further highlighted the critical need for novel drug discovery and development in this field. One of the biggest challenges in schizophrenia-related drug discovery is to find an appropriate animal model of the illness so that novel hypotheses can be tested at the basic science level. A number of pharmacological, genetic, and neurodevelopmental models have been introduced; however, none of these models has been rigorously evaluated for translational relevance or to satisfy requirements of “face,” “construct” and “predictive” validity. Given the apparent polygenic nature of schizophrenia and the limited translational significance of pharmacological models, neurodevelopmental models may offer the best chance of success. The purpose of this review is to provide a general overview of the various neurodevelopmental models of schizophrenia that have been introduced to date, and to summarize their behavioral and neurochemical phenotypes that may be useful from a drug discovery and development standpoint. While it may be that, in the final analysis, no single animal model will satisfy all the requirements necessary for drug discovery purposes, several of the models may be useful for modeling various phenomenological and pathophysiological components of schizophrenia that could be targeted independently with separate molecules or multi-target drugs. PMID:20643635

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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...

  18. 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...

  19. 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...

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Mesenchymal Stem Cells for Vascular Target Discovery in Breast Cancer-Associated Angiogenesis

    DTIC Science & Technology

    2005-09-01

    investigative gene discovery program to identify new genes involved in blood vessel formation. MSCs, a normal cell type from the bone marrow, can spontaneously...34antiangiogenesis" targets for either a classic pharmacological approach or for cell and gene therapy therapeutic strategies. The utilization of...compounds. 15. SUBJECT TERMS Marrow stroma, breast cancer, angiogenesis gene therapy, gene discovery 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18

  10. 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.

  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. 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.

  14. 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.

  15. 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.

  16. STS-131: Discovery Does Backflip at Station

    NASA Video Gallery

    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...

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  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. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. Eye Involvement in TSC

    MedlinePlus

    ... Privacy Policy Sitemap Learn Engage Donate About TSC Eyes Campbell (1905) first described the eye involvement in ... some form of eye involvement. Nonretinal and Retinal Eye Findings Facial angiofibromas may involve the eyelids of ...

  12. 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

  13. 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.

  14. 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.

  15. 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!

  16. 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.

  17. 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

  18. 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.…

  19. Open Access High Throughput Drug Discovery in the Public Domain: A Mount Everest in the Making

    PubMed Central

    Roy, Anuradha; McDonald, Peter R.; Sittampalam, Sitta; Chaguturu, Rathnam

    2013-01-01

    High throughput screening (HTS) facilitates screening large numbers of compounds against a biochemical target of interest using validated biological or biophysical assays. In recent years, a significant number of drugs in clinical trails originated from HTS campaigns, validating HTS as a bona fide mechanism for hit finding. In the current drug discovery landscape, the pharmaceutical industry is embracing open innovation strategies with academia to maximize their research capabilities and to feed their drug discovery pipeline. The goals of academic research have therefore expanded from target identification and validation to probe discovery, chemical genomics, and compound library screening. This trend is reflected in the emergence of HTS centers in the public domain over the past decade, ranging in size from modestly equipped academic screening centers to well endowed Molecular Libraries Probe Centers Network (MLPCN) centers funded by the NIH Roadmap initiative. These centers facilitate a comprehensive approach to probe discovery in academia and utilize both classical and cutting-edge assay technologies for executing primary and secondary screening campaigns. The various facets of academic HTS centers as well as their implications on technology transfer and drug discovery are discussed, and a roadmap for successful drug discovery in the public domain is presented. New lead discovery against therapeutic targets, especially those involving the rare and neglected diseases, is indeed a Mount Everestonian size task, and requires diligent implementation of pharmaceutical industry’s best practices for a successful outcome. PMID:20809896

  20. Function-driven discovery of disease genes in zebrafish using an integrated genomics big data resource

    PubMed Central

    Shim, Hongseok; Kim, Ji Hyun; Kim, Chan Yeong; Hwang, Sohyun; Kim, Hyojin; Yang, Sunmo; Lee, Ji Eun; Lee, Insuk

    2016-01-01

    Whole exome sequencing (WES) accelerates disease gene discovery using rare genetic variants, but further statistical and functional evidence is required to avoid false-discovery. To complement variant-driven disease gene discovery, here we present function-driven disease gene discovery in zebrafish (Danio rerio), a promising human disease model owing to its high anatomical and genomic similarity to humans. To facilitate zebrafish-based function-driven disease gene discovery, we developed a genome-scale co-functional network of zebrafish genes, DanioNet (www.inetbio.org/danionet), which was constructed by Bayesian integration of genomics big data. Rigorous statistical assessment confirmed the high prediction capacity of DanioNet for a wide variety of human diseases. To demonstrate the feasibility of the function-driven disease gene discovery using DanioNet, we predicted genes for ciliopathies and performed experimental validation for eight candidate genes. We also validated the existence of heterozygous rare variants in the candidate genes of individuals with ciliopathies yet not in controls derived from the UK10K consortium, suggesting that these variants are potentially involved in enhancing the risk of ciliopathies. These results showed that an integrated genomics big data for a model animal of diseases can expand our opportunity for harnessing WES data in disease gene discovery. PMID:27903883

  1. Open access high throughput drug discovery in the public domain: a Mount Everest in the making.

    PubMed

    Roy, Anuradha; McDonald, Peter R; Sittampalam, Sitta; Chaguturu, Rathnam

    2010-11-01

    High throughput screening (HTS) facilitates screening large numbers of compounds against a biochemical target of interest using validated biological or biophysical assays. In recent years, a significant number of drugs in clinical trails originated from HTS campaigns, validating HTS as a bona fide mechanism for hit finding. In the current drug discovery landscape, the pharmaceutical industry is embracing open innovation strategies with academia to maximize their research capabilities and to feed their drug discovery pipeline. The goals of academic research have therefore expanded from target identification and validation to probe discovery, chemical genomics, and compound library screening. This trend is reflected in the emergence of HTS centers in the public domain over the past decade, ranging in size from modestly equipped academic screening centers to well endowed Molecular Libraries Probe Centers Network (MLPCN) centers funded by the NIH Roadmap initiative. These centers facilitate a comprehensive approach to probe discovery in academia and utilize both classical and cutting-edge assay technologies for executing primary and secondary screening campaigns. The various facets of academic HTS centers as well as their implications on technology transfer and drug discovery are discussed, and a roadmap for successful drug discovery in the public domain is presented. New lead discovery against therapeutic targets, especially those involving the rare and neglected diseases, is indeed a Mount Everestonian size task, and requires diligent implementation of pharmaceutical industry's best practices for a successful outcome.

  2. 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

  3. 15 CFR 719.10 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter, not privileged, which is relevant to the subject matter of the pending proceeding. The provisions of..., oppression, or undue burden or expense. These orders may include limitations on the scope, method, time...

  4. 42 CFR 405.1037 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... review of a discovery ruling, if the MAC does not grant review or take own motion review within the time... as a party. (2) The ALJ may permit discovery of a matter that is relevant to the specific subject matter of the ALJ hearing, provided the matter is not privileged or otherwise protected from...

  5. 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....

  6. 40 CFR 209.22 - Other discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Other discovery. 209.22 Section 209.22 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS RULES OF... Orders Issued Under Section 11(d) of the Noise Control Act § 209.22 Other discovery. (a)...

  7. Promising Practices in Instruction of Discovery Tools

    ERIC Educational Resources Information Center

    Buck, Stefanie; Steffy, Christina

    2013-01-01

    Libraries are continually changing to meet the needs of users; this includes implementing discovery tools, also referred to as web-scale discovery tools, to make searching library resources easier. Because these tools are so new, it is difficult to establish definitive best practices for teaching these tools; however, promising practices are…

  8. 47 CFR 65.105 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Discovery. 65.105 Section 65.105 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERSTATE RATE OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Procedures § 65.105 Discovery. (a)...

  9. 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...

  10. Security Services Discovery by ATM Endsystems

    SciTech Connect

    Sholander, Peter; Tarman, Thomas

    1999-07-15

    This contribution proposes strawman techniques for Security Service Discovery by ATM endsystems in ATM networks. Candidate techniques include ILMI extensions, ANS extensions and new ATM anycast addresses. Another option is a new protocol based on an IETF service discovery protocol, such as Service Location Protocol (SLP). Finally, this contribution provides strawman requirements for Security-Based Routing in ATM networks.

  11. Accounting for discovery bias in genomic prediction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to evaluate an approach to mitigating discovery bias in genomic prediction. Accuracy may be improved by placing greater emphasis on regions of the genome expected to be more influential on a trait. Methods emphasizing regions result in a phenomenon known as “discovery bias” if info...

  12. Knowledge Discovery from Databases: An Introductory Review.

    ERIC Educational Resources Information Center

    Vickery, Brian

    1997-01-01

    Introduces new procedures being used to extract knowledge from databases and discusses rationales for developing knowledge discovery methods. Methods are described for such techniques as classification, clustering, and the detection of deviations from pre-established norms. Examines potential uses of knowledge discovery in the information field.…

  13. A Discovery Chemistry Experiment on Buffers

    ERIC Educational Resources Information Center

    Kulevich, Suzanne E.; Herrick, Richard S.; Mills, Kenneth V.

    2014-01-01

    The Holy Cross Chemistry Department has designed and implemented an experiment on buffers as part of our Discovery Chemistry curriculum. The pedagogical philosophy of Discovery Chemistry is to make the laboratory the focal point of learning for students in their first two years of undergraduate instruction. We first pose questions in prelaboratory…

  14. 5 CFR 1201.73 - Discovery procedures.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Discovery procedures. 1201.73 Section 1201.73 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION AND PROCEDURES PRACTICES... conference. (e) Limits on the number of discovery requests. (1) Absent prior approval by the...

  15. 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....

  16. 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....

  17. 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....

  18. 31 CFR 10.71 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... law; (7) The material sought relates to mental impressions, conclusions, or legal theories of any... things, infer that the information would be adverse to the party failing to provide it, exclude the information from evidence or issue a decision by default. (f) Other discovery. No discovery other than...

  19. 31 CFR 10.71 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... law; (7) The material sought relates to mental impressions, conclusions, or legal theories of any... things, infer that the information would be adverse to the party failing to provide it, exclude the information from evidence or issue a decision by default. (f) Other discovery. No discovery other than...

  20. 31 CFR 10.71 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... law; (7) The material sought relates to mental impressions, conclusions, or legal theories of any... things, infer that the information would be adverse to the party failing to provide it, exclude the information from evidence or issue a decision by default. (f) Other discovery. No discovery other than...

  1. 31 CFR 10.71 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... law; (7) The material sought relates to mental impressions, conclusions, or legal theories of any... things, infer that the information would be adverse to the party failing to provide it, exclude the information from evidence or issue a decision by default. (f) Other discovery. No discovery other than...

  2. 42 CFR 426.532 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 10 written interrogatory questions, relating to a specific NCD. (d) Types of documents. For the... interpreted to require the creation of a document. (e) Types of discovery not available. Requests for...) Notification. The Board notifies all parties in writing when the discovery period will be closed....

  3. 42 CFR 426.532 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... submission of up to 10 written interrogatory questions, relating to a specific NCD. (d) Types of documents... be interpreted to require the creation of a document. (e) Types of discovery not available. Requests... information. (g) Notification. The Board notifies all parties in writing when the discovery period will...

  4. 42 CFR 426.432 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... written interrogatory questions, relating to a specific LCD. (d) Types of documents. For the purpose of... require the creation of a document. (e) Types of discovery not available. Requests for admissions... notifies all parties in writing when the discovery period closes....

  5. 42 CFR 426.532 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 10 written interrogatory questions, relating to a specific NCD. (d) Types of documents. For the... interpreted to require the creation of a document. (e) Types of discovery not available. Requests for...) Notification. The Board notifies all parties in writing when the discovery period will be closed....

  6. 45 CFR 213.23a - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES PRACTICE AND PROCEDURE FOR HEARINGS TO... to conduct discovery (including depositions) against opposing parties. Rules 26-37 of the Federal... control discovery so as to prevent undue delay in the conduct of the hearing. Upon the failure of...

  7. 4 CFR 22.8 - General Discovery Procedures [Rule 8].

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... OFFICE CONTRACT APPEALS BOARD § 22.8 General Discovery Procedures . (a) General policy and methods of discovery. The parties are encouraged to engage in voluntary discovery procedures and may obtain discovery... 4 Accounts 1 2010-01-01 2010-01-01 false General Discovery Procedures . 22.8 Section 22.8...

  8. 19 CFR 210.27 - General provisions governing discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Discovery and Compulsory Process § 210.27 General provisions governing discovery. (a) Discovery methods. The parties to an investigation may obtain discovery... 19 Customs Duties 3 2010-04-01 2010-04-01 false General provisions governing discovery....

  9. 28 CFR 68.18 - Discovery-general provisions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... discovery may be had only by a method of discovery other than that selected by the party seeking discovery... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery-general provisions. 68.18... Discovery—general provisions. (a) General. Parties may obtain discovery by one or more of the...

  10. Human brain evolution: from gene discovery to phenotype discovery.

    PubMed

    Preuss, Todd M

    2012-06-26

    The rise of comparative genomics and related technologies has added important new dimensions to the study of human evolution. Our knowledge of the genes that underwent expression changes or were targets of positive selection in human evolution is rapidly increasing, as is our knowledge of gene duplications, translocations, and deletions. It is now clear that the genetic differences between humans and chimpanzees are far more extensive than previously thought; their genomes are not 98% or 99% identical. Despite the rapid growth in our understanding of the evolution of the human genome, our understanding of the relationship between genetic changes and phenotypic changes is tenuous. This is true even for the most intensively studied gene, FOXP2, which underwent positive selection in the human terminal lineage and is thought to have played an important role in the evolution of human speech and language. In part, the difficulty of connecting genes to phenotypes reflects our generally poor knowledge of human phenotypic specializations, as well as the difficulty of interpreting the consequences of genetic changes in species that are not amenable to invasive research. On the positive side, investigations of FOXP2, along with genomewide surveys of gene-expression changes and selection-driven sequence changes, offer the opportunity for "phenotype discovery," providing clues to human phenotypic specializations that were previously unsuspected. What is more, at least some of the specializations that have been proposed are amenable to testing with noninvasive experimental techniques appropriate for the study of humans and apes.

  11. The discovery of the periodic table as a case of simultaneous discovery.

    PubMed

    Scerri, Eric

    2015-03-13

    The article examines the question of priority and simultaneous discovery in the context of the discovery of the periodic system. It is argued that rather than being anomalous, simultaneous discovery is the rule. Moreover, I argue that the discovery of the periodic system by at least six authors in over a period of 7 years represents one of the best examples of a multiple discovery. This notion is supported by a new view of the evolutionary development of science through a mechanism that is dubbed Sci-Gaia by analogy with Lovelock's Gaia hypothesis.

  12. The Discovery of the Tau Lepton and the Changes in Elementary Particle Physics in 40 Years

    DOE R&D Accomplishments Database

    Perl, M.

    2003-10-22

    This is a history of my discovery of the tau lepton in the 1970s for which I was awarded the Nobel Prize in Physics. I have previously described some aspects of the discovery. In 1996 in my collection of papers entitled, ''Reflections on Experimental Science,'' I gave a straightforward account of the experimental method and the physics involved in the discovery as an introduction to the collection. In a 2002 paper written with Mary A. Meyer published in the journal ''Theoria et Historia Scientiarum'' I used the story of the discovery to outline my thoughts on the practice of experimental science. That 2002 paper was written primarily for young women and men who are beginning their lives in science and it was based on a lecture given at Los Alamos National Laboratory. Some of the historical material in this paper has appeared in those two earlier papers.

  13. Swift: 10 Years of Discovery

    NASA Astrophysics Data System (ADS)

    The conference Swift: 10 years of discovery was held in Roma at La Sapienza University on Dec. 2-5 2014 to celebrate 10 years of Swift successes. Thanks to a large attendance and a lively program, it provided the opportunity to review recent advances of our knowledge of the high-energy transient Universe both from the observational and theoretical sides. When Swift was launched on November 20, 2004, its prime objective was to chase Gamma-Ray Bursts and deepen our knowledge of these cosmic explosions. And so it did, unveiling the secrets of long and short GRBs. However, its multi-wavelength instrumentation and fast scheduling capabilities made it the most versatile mission ever flown. Besides GRBs, Swift has observed, and contributed to our understanding of, an impressive variety of targets including AGNs, supernovae, pulsars, microquasars, novae, variable stars, comets, and much more. Swift is continuously discovering rare and surprising events distributed over a wide range of redshifts, out to the most distant transient objects in the Universe. Such a trove of discoveries has been addressed during the conference with sessions dedicated to each class of events. Indeed, the conference in Rome was a spectacular celebration of the Swift 10th anniversary. It included sessions on all types of transient and steady sources. Top scientists from around the world gave invited and contributed talks. There was a large poster session, sumptuous lunches, news interviews and a glorious banquet with officials attending from INAF and ASI. All the presentations, as well as several conference pictures, can be found in the conference website (http://www.brera.inaf.it/Swift10/Welcome.html). These proceedings have been collected owing to the efforts of Paolo D’Avanzo who has followed each paper from submission to final acceptance. Our warmest thanks to Paolo for all his work. The Conference has been made possible by the support from La Sapienza University as well as from the ARAP

  14. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    NASA Astrophysics Data System (ADS)

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  15. Discovery: Under the Microscope at Kennedy Space Center

    NASA Technical Reports Server (NTRS)

    Howard, Philip M.

    2013-01-01

    The National Aeronautics & Space Administration (NASA) is known for discovery, exploration, and advancement of knowledge. Since the days of Leeuwenhoek, microscopy has been at the forefront of discovery and knowledge. No truer is that statement than today at Kennedy Space Center (KSC), where microscopy plays a major role in contamination identification and is an integral part of failure analysis. Space exploration involves flight hardware undergoing rigorous "visually clean" inspections at every step of processing. The unknown contaminants that are discovered on these inspections can directly impact the mission by decreasing performance of sensors and scientific detectors on spacecraft and satellites, acting as micrometeorites, damaging critical sealing surfaces, and causing hazards to the crew of manned missions. This talk will discuss how microscopy has played a major role in all aspects of space port operations at KSC. Case studies will highlight years of analysis at the Materials Science Division including facility and payload contamination for the Navigation Signal Timing and Ranging Global Positioning Satellites (NA VST AR GPS) missions, quality control monitoring of monomethyl hydrazine fuel procurement for launch vehicle operations, Shuttle Solids Rocket Booster (SRB) foam processing failure analysis, and Space Shuttle Main Engine Cut-off (ECO) flight sensor anomaly analysis. What I hope to share with my fellow microscopists is some of the excitement of microscopy and how its discoveries has led to hardware processing, that has helped enable the successful launch of vehicles and space flight missions here at Kennedy Space Center.

  16. Ecosystem discovery: Measuring clean energy innovation ecosystems through knowledge discovery and mapping techniques

    DOE PAGES

    Lin, Jessica; Chinthavali, Supriya; Stahl, Chelsey Dunivan; ...

    2016-10-01

    The term ‘innovation ecosystem’ is often utilized, but rarely quantified. Oak Ridge National Lab conducted a ground-breaking application of natural language processing, link analysis and other computational techniques to transform text and numerical data into metrics on clean energy innovation activity and geography for the U.S. Department of Energy. The project demonstrates that a machine-assisted methodology gives the user a replicable method to rapidly identify, quantify and characterize clean energy innovation ecosystems. EPSA advanced a novel definition for clean energy innovation ecosystem as the overlap of five Ecosystem Components: 1) nascent clean energy indicators, 2) investors, 3) enabling environment, 4)more » networking assets and 5) large companies. The tool was created with the flexibility to allow the user to choose the weights of each of the five ecosystem components and the subcomponents. This flexibility allows the user to visualize different subsets of data as well as the composite IE rank. In an independent parallel effort, a DOE analyst in EPSA developed a short list of 22 top US clean energy innovation ecosystems; the Ecosystem Discovery tool was able to identify over 90% of the analyst-reported ecosystems. Full validation and calibration remain outstanding tasks. The tool and the underlying datasets have the potential to address a number of important policy questions. The initial broad list of U.S. clean energy innovation ecosystems, with geographic area, technology focus, and list and types of involved organizations can help describe regional technology activities and capabilities. The implementation of knowledge discovery techniques also revealed both the potential and limitations of an automatic machine extraction methodology to gather ecosystem component data. The project demonstrates that a machine-assisted methodology gives the user a replicable method to rapidly identify, quantify, and characterize clean energy innovation

  17. Ecosystem discovery: Measuring clean energy innovation ecosystems through knowledge discovery and mapping techniques

    SciTech Connect

    Lin, Jessica; Chinthavali, Supriya; Stahl, Chelsey Dunivan; Stahl, Christopher; Lee, Sangkeun; Shankar, Mallikarjun

    2016-10-01

    The term ‘innovation ecosystem’ is often utilized, but rarely quantified. Oak Ridge National Lab conducted a ground-breaking application of natural language processing, link analysis and other computational techniques to transform text and numerical data into metrics on clean energy innovation activity and geography for the U.S. Department of Energy. The project demonstrates that a machine-assisted methodology gives the user a replicable method to rapidly identify, quantify and characterize clean energy innovation ecosystems. EPSA advanced a novel definition for clean energy innovation ecosystem as the overlap of five Ecosystem Components: 1) nascent clean energy indicators, 2) investors, 3) enabling environment, 4) networking assets and 5) large companies. The tool was created with the flexibility to allow the user to choose the weights of each of the five ecosystem components and the subcomponents. This flexibility allows the user to visualize different subsets of data as well as the composite IE rank. In an independent parallel effort, a DOE analyst in EPSA developed a short list of 22 top US clean energy innovation ecosystems; the Ecosystem Discovery tool was able to identify over 90% of the analyst-reported ecosystems. Full validation and calibration remain outstanding tasks. The tool and the underlying datasets have the potential to address a number of important policy questions. The initial broad list of U.S. clean energy innovation ecosystems, with geographic area, technology focus, and list and types of involved organizations can help describe regional technology activities and capabilities. The implementation of knowledge discovery techniques also revealed both the potential and limitations of an automatic machine extraction methodology to gather ecosystem component data. The project demonstrates that a machine-assisted methodology gives the user a replicable method to rapidly identify, quantify, and characterize clean energy innovation ecosystems.

  18. Discovery of Grooves on Gaspra

    USGS Publications Warehouse

    Veverka, J.; Thomas, P.; Simonelli, D.; Belton, M.J.S.; Carr, M.; Chapman, C.; Davies, M.E.; Greeley, R.; Greenberg, R.; Head, J.; Klaasen, K.; Johnson, T.V.; Morrison, D.; Neukum, G.

    1994-01-01

    We report the discovery of grooves in Galileo high-resolution images of Gaspra. These features, previously seen only on Mars' satellite Phobos, are most likely related to severe impacts. Grooves on Gaspra occur as linear and pitted depressions, typically 100-200 m wide, 0.8 to 2.5 km long, and 10-20 m deep. Most occur in two major groups, one of which trends approximately parallel to the asteroid's long axis, but is offset by some 15??; the other is approximately perpendicular to this trend. The first of these directions falls along a family of planes which parallel three extensive flat facets identified by Thomas et al., Icarus 107. The occurrence of grooves on Gaspra is consistent with other indications (irregular shape, cratering record) that this asteroid has evolved through a violent collisional history. The bodywide congruence of major groove directions and other structural elements suggests that present-day Gaspra is a globally coherent body. ?? 1994 Academic Press. All rights reserved.

  19. NIF Discovery Science Eagle Nebula

    NASA Astrophysics Data System (ADS)

    Kane, Jave; Martinez, David; Pound, Marc; Heeter, Robert; Huntington, Channing; Casner, Alexis; Villette, Bruno; Mancini, Roberto

    2016-10-01

    For almost 20 years a team of astronomers, theorists and experimentalists have investigated the creation of the famous Pillars of the Eagle Nebula and similar parsec-scale structures at the boundaries of HII regions in molecular hydrogen clouds, using a combination of astronomical observations, astrophysical simulations, and recently, scaled laboratory experiments. Eagle Nebula, one of the National Ignition Facility (NIF) Discovery Science programs, has completed four NIF shots to study the dense `shadowing' model of pillar formation, and been awarded more shots to study the `cometary' model. These experiments require a long-duration drive, 30 ns or longer, to generate deeply nonlinear ablative hydrodynamics. A novel x-ray source featuring multiple UV-driven hohlraums driven is used. The source directionally illuminates a science package, mimicking a cluster of stars. The first four NIF shots generated radiographs of shadowing-model pillars, and suggested that cometary structures can be generated. The velocity and column density profiles of the NIF shadowing and cometary pillars have been compared with observations of the Eagle Pillars made at millimeter observatories, and indicate cometary growth is key to matching observations. Supported in part by a Grant from the DOE OFES HEDLP program. Prepared by LLNL under Contract DE-AC52-07NA27344.

  20. Knowledge Discovery from Vibration Measurements

    PubMed Central

    Li, Jian; Wang, Daoyao

    2014-01-01

    The framework as well as the particular algorithms of pattern recognition process is widely adopted in structural health monitoring (SHM). However, as a part of the overall process of knowledge discovery from data bases (KDD), the results of pattern recognition are only changes and patterns of changes of data features. In this paper, based on the similarity between KDD and SHM and considering the particularity of SHM problems, a four-step framework of SHM is proposed which extends the final goal of SHM from detecting damages to extracting knowledge to facilitate decision making. The purposes and proper methods of each step of this framework are discussed. To demonstrate the proposed SHM framework, a specific SHM method which is composed by the second order structural parameter identification, statistical control chart analysis, and system reliability analysis is then presented. To examine the performance of this SHM method, real sensor data measured from a lab size steel bridge model structure are used. The developed four-step framework of SHM has the potential to clarify the process of SHM to facilitate the further development of SHM techniques. PMID:24574933

  1. Knowledge discovery from vibration measurements.

    PubMed

    Deng, Jun; Li, Jian; Wang, Daoyao

    2014-01-01

    The framework as well as the particular algorithms of pattern recognition process is widely adopted in structural health monitoring (SHM). However, as a part of the overall process of knowledge discovery from data bases (KDD), the results of pattern recognition are only changes and patterns of changes of data features. In this paper, based on the similarity between KDD and SHM and considering the particularity of SHM problems, a four-step framework of SHM is proposed which extends the final goal of SHM from detecting damages to extracting knowledge to facilitate decision making. The purposes and proper methods of each step of this framework are discussed. To demonstrate the proposed SHM framework, a specific SHM method which is composed by the second order structural parameter identification, statistical control chart analysis, and system reliability analysis is then presented. To examine the performance of this SHM method, real sensor data measured from a lab size steel bridge model structure are used. The developed four-step framework of SHM has the potential to clarify the process of SHM to facilitate the further development of SHM techniques.

  2. Materials discovery through crystal growth

    NASA Astrophysics Data System (ADS)

    zur Loye, Hans-Conrad

    2016-04-01

    The discovery of new materials and associated desirable properties has been a driving force behind chemical innovation for centuries. When we look at some of the many recent technological advances, and how widespread and significant their impact has been, we appreciate how much they have relied on new materials. The increase in hard drive storage capacity due to new giant magneto-resistive materials, the ever-shrinking cell phone due to improved microwave dielectric materials, the enhancement in lithium battery storage capacity due to new intercalation materials, or the improved capacitor due to new ferroelectric materials are all excellent examples. How were these materials discovered? While there is no single answer, in all cases there was a First-Material, the archetype in which the phenomenon was first observed, the one that led to further investigations and the subsequent preparation of improved 2nd or 3rd generation materials. It is this First-Material, the archetype, that was discovered - often via crystal growth.

  3. Genetic algorithms for route discovery.

    PubMed

    Gelenbe, Erol; Liu, Peixiang; Lainé, Jeremy

    2006-12-01

    Packet routing in networks requires knowledge about available paths, which can be either acquired dynamically while the traffic is being forwarded, or statically (in advance) based on prior information of a network's topology. This paper describes an experimental investigation of path discovery using genetic algorithms (GAs). We start with the quality-of-service (QoS)-driven routing protocol called "cognitive packet network" (CPN), which uses smart packets (SPs) to dynamically select routes in a distributed autonomic manner based on a user's QoS requirements. We extend it by introducing a GA at the source routers, which modifies and filters the paths discovered by the CPN. The GA can combine the paths that were previously discovered to create new untested but valid source-to-destination paths, which are then selected on the basis of their "fitness." We present an implementation of this approach, where the GA runs in background mode so as not to overload the ingress routers. Measurements conducted on a network test bed indicate that when the background-traffic load of the network is light to medium, the GA can result in improved QoS. When the background-traffic load is high, it appears that the use of the GA may be detrimental to the QoS experienced by users as compared to CPN routing because the GA uses less timely state information in its decision making.

  4. Automatic discovery of optimal classes

    NASA Technical Reports Server (NTRS)

    Cheeseman, Peter; Stutz, John; Freeman, Don; Self, Matthew

    1986-01-01

    A criterion, based on Bayes' theorem, is described that defines the optimal set of classes (a classification) for a given set of examples. This criterion is transformed into an equivalent minimum message length criterion with an intuitive information interpretation. This criterion does not require that the number of classes be specified in advance, this is determined by the data. The minimum message length criterion includes the message length required to describe the classes, so there is a built in bias against adding new classes unless they lead to a reduction in the message length required to describe the data. Unfortunately, the search space of possible classifications is too large to search exhaustively, so heuristic search methods, such as simulated annealing, are applied. Tutored learning and probabilistic prediction in particular cases are an important indirect result of optimal class discovery. Extensions to the basic class induction program include the ability to combine category and real value data, hierarchical classes, independent classifications and deciding for each class which attributes are relevant.

  5. A Metadata based Knowledge Discovery Methodology for Seeding Translational Research.

    PubMed

    Kothari, Cartik R; Payne, Philip R O

    2015-01-01

    In this paper, we present a semantic, metadata based knowledge discovery methodology for identifying teams of researchers from diverse backgrounds who can collaborate on interdisciplinary research projects: projects in areas that have been identified as high-impact areas at The Ohio State University. This methodology involves the semantic annotation of keywords and the postulation of semantic metrics to improve the efficiency of the path exploration algorithm as well as to rank the results. Results indicate that our methodology can discover groups of experts from diverse areas who can collaborate on translational research projects.

  6. 49 CFR 386.41 - Stipulations regarding discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... other methods of discovery. ... 49 Transportation 5 2010-10-01 2010-10-01 false Stipulations regarding discovery. 386.41 Section... MATERIALS PROCEEDINGS General Rules and Hearings § 386.41 Stipulations regarding discovery. Unless...

  7. BOSS discovery of 3 probable nearby supernovae

    NASA Astrophysics Data System (ADS)

    Parker, Stuart; Marples, Peter; Bock, Greg; Drecher, Colin; Search, Pat Pearl Backyard Observatory Supernova

    2017-03-01

    During the on going BOSS sky survey on 2017 March 7th and 8th using data from Parkdale Observatory, Stuart Parker, Canterbury, New Zealand, reports the discovery of 3 apparent supernovae on a 30-s Clear filter CCD image (limiting mag 18) taken by himself with a 30-cm Astro-Tech AT12RC Ritchey-Chretien astrograph (+ ST10 camera) . AT2017caw RA=08:07:50.10, DEC=-61:46:15.60, Discovery date=2017-03-08.078, Discovery mag=18 Filter:Clear-offset 1.5W 14.6S AT2017bzc RA=23:16:14.69, DEC=-42:34:10.90, Discovery date=2017-03-07.219, Discovery mag=12.8 Filder:Clear- offset 45E 50N AT2017bzb RA=22:57:17.30, DEC=-41:00:57.60, Discovery date=2017-03-07.213, Discovery mag=13 Filter: Clear-offset 12W 196N AT2017bzb and AT2017bzc are very early morning targets being very low just before sunrise.

  8. The University of New Mexico Center for Molecular Discovery

    PubMed Central

    Edwards, Bruce S.; Gouveia, Kristine; Oprea, Tudor I.; Sklar, Larry A.

    2015-01-01

    The University of New Mexico Center for Molecular Discovery (UNMCMD) is an academic research center that specializes in discovery using high throughput flow cytometry (HTFC) integrated with virtual screening, as well as knowledge mining and drug informatics. With a primary focus on identifying small molecules that can be used as chemical probes and as leads for drug discovery, it is a central core resource for research and translational activities at UNM that supports implementation and management of funded screening projects as well as “up-front” services such as consulting for project design and implementation, assistance in assay development and generation of preliminary data for pilot projects in support of competitive grant applications. The HTFC platform in current use represents advanced, proprietary technology developed at UNM that is now routinely capable of processing bioassays arrayed in 96-, 384- and 1536-well formats at throughputs of 60,000 or more wells per day. Key programs at UNMCMD include screening of research targets submitted by the international community through NIH’s Molecular Libraries Program; a multi-year effort involving translational partnerships at UNM directed towards drug repurposing - identifying new uses for clinically approved drugs; and a recently established personalized medicine initiative for advancing cancer therapy by the application of “smart” oncology drugs in selected patients based on response patterns of their cancer cells in vitro. UNMCMD discoveries, innovation, and translation have contributed to a wealth of inventions, patents, licenses and publications, as well as startup companies, clinical trials and a multiplicity of domestic and international collaborative partnerships to further the research enterprise. PMID:24409953

  9. The University of New Mexico Center for Molecular Discovery.

    PubMed

    Edwards, Bruce S; Gouveia, Kristine; Oprea, Tudor I; Sklar, Larry A

    2014-03-01

    The University of New Mexico Center for Molecular Discovery (UNMCMD) is an academic research center that specializes in discovery using high throughput flow cytometry (HTFC) integrated with virtual screening, as well as knowledge mining and drug informatics. With a primary focus on identifying small molecules that can be used as chemical probes and as leads for drug discovery, it is a central core resource for research and translational activities at UNM that supports implementation and management of funded screening projects as well as "up-front" services such as consulting for project design and implementation, assistance in assay development and generation of preliminary data for pilot projects in support of competitive grant applications. The HTFC platform in current use represents advanced, proprietary technology developed at UNM that is now routinely capable of processing bioassays arrayed in 96-, 384- and 1536-well formats at throughputs of 60,000 or more wells per day. Key programs at UNMCMD include screening of research targets submitted by the international community through NIH's Molecular Libraries Program; a multi-year effort involving translational partnerships at UNM directed towards drug repurposing - identifying new uses for clinically approved drugs; and a recently established personalized medicine initiative for advancing cancer therapy by the application of "smart" oncology drugs in selected patients based on response patterns of their cancer cells in vitro. UNMCMD discoveries, innovation, and translation have contributed to a wealth of inventions, patents, licenses and publications, as well as startup companies, clinical trials and a multiplicity of domestic and international collaborative partnerships to further the research enterprise.

  10. Open PHACTS: semantic interoperability for drug discovery.

    PubMed

    Williams, Antony J; Harland, Lee; Groth, Paul; Pettifer, Stephen; Chichester, Christine; Willighagen, Egon L; Evelo, Chris T; Blomberg, Niklas; Ecker, Gerhard; Goble, Carole; Mons, Barend

    2012-11-01

    Open PHACTS is a public-private partnership between academia, publishers, small and medium sized enterprises and pharmaceutical companies. The goal of the project is to deliver and sustain an 'open pharmacological space' using and enhancing state-of-the-art semantic web standards and technologies. It is focused on practical and robust applications to solve specific questions in drug discovery research. OPS is intended to facilitate improvements in drug discovery in academia and industry and to support open innovation and in-house non-public drug discovery research. This paper lays out the challenges and how the Open PHACTS project is hoping to address these challenges technically and socially.

  11. Genomics and transcriptomics in drug discovery.

    PubMed

    Dopazo, Joaquin

    2014-02-01

    The popularization of genomic high-throughput technologies is causing a revolution in biomedical research and, particularly, is transforming the field of drug discovery. Systems biology offers a framework to understand the extensive human genetic heterogeneity revealed by genomic sequencing in the context of the network of functional, regulatory and physical protein-drug interactions. Thus, approaches to find biomarkers and therapeutic targets will have to take into account the complex system nature of the relationships of the proteins with the disease. Pharmaceutical companies will have to reorient their drug discovery strategies considering the human genetic heterogeneity. Consequently, modeling and computational data analysis will have an increasingly important role in drug discovery.

  12. 5 CFR 1201.72 - Explanation and scope of discovery.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... information that appears reasonably calculated to lead to the discovery of admissible evidence. This... location of persons with knowledge of relevant facts. Discovery requests that are directed to...

  13. Home Fires Involving Grills

    MedlinePlus

    ... fires were fueled by gas while 13% used charcoal or other solid fuel. Gas grills were involved ... structure fires and 4,300 outdoor fires annually. Charcoal or other solid-fueled grills were involved in ...

  14. The discovery of Maxwell's equations

    NASA Astrophysics Data System (ADS)

    Everitt, Francis

    2012-02-01

    In January 1865, Maxwell at age 34 wrote a letter to his cousin Charles Cay describing various doings, including his work on the viscosity of gases and a visit from two of the world's leading oculists to inspect the eyes of his dog ``Spice''. He added, ``I have also a paper afloat, with an electromagnetic theory of light, which, till I am convinced to the contrary, I hold to be great guns.'' That paper ``A Dynamical Theory of the Electromagnetic Field'' was his fourth on the subject. It was followed in 1868 by another, and then in 1873 by his massive two volume Treatise on Electricity and Magnetism. Even so, by the time of his death in 1879 as he was beginning a radically revised edition of the Treatise, much remained to be done. We celebrate here the 150^th anniversary of Maxwell's first astonished realization in 1862 of the link between electromagnetism and light. So revolutionary was this that 15 or more years went by before Lorentz, Poynting, FitzGerald, and others came to address it, sometimes with improvements, sometimes not. Not until 1888 did Hertz make the essential experimental discovery of radio waves. What is so remarkable about Maxwell's five papers is that each presents a complete view of the subject radically different from the one before. I shall say something about each, emphasizing in particular Maxwell's most unexpected idea, the displacement current, so vastly more interesting than the accounts of it found in textbooks today. Beyond lie other surprises. The concept of gauge invariance, and the role the vector potential would play in defining the canonical momentum of the electron, both go back to Maxwell. In 1872 came a paper ``On the Mathematical Classification of Physical Quantities'', which stands as an education in itself. Amid much else, there for the first time appears the distinction between axial and polar vectors and those new operational concepts related to quaternion theory: curl, divergence, and gradient.

  15. Systems biology and biomarker discovery

    SciTech Connect

    Rodland, Karin D.

    2010-12-01

    Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

  16. Involving Parents at School

    ERIC Educational Resources Information Center

    Montgomery, Joel R.

    2008-01-01

    This working paper explores reasons to encourage parents of English language learners (ELLs) to be involved in the learning process at the middle school level. Barriers to parental involvement of language minority students will be identified and successful, research-based strategies to increase parental involvement will be introduced. Five…

  17. Involving Faculty in Planning.

    ERIC Educational Resources Information Center

    Andrew, Lloyd D.

    1979-01-01

    Firm planning objectives, clearly stated relationships to overall institutional objectives, faculty involvement, and active leadership are advocated for successful academic planning. Faculty involvement is dependent on the strength of the technical, marketing, and budgeting staffs, and involvement in the planning process may kindle faculty…

  18. Gubernatorial Involvement in Education.

    ERIC Educational Resources Information Center

    Hines, Edward R.

    This research on 12 States' gubernatorial involvement in State educational policy formation investigates four functional stages of that involvement--issue definition, proposal formulation, support mobilization, and decision enactment. Drawing on the Educational Governance Project information and interviews, a gubernatorial involvement index was…

  19. NASA's Kepler Mission Announces Latest Discoveries

    NASA Video Gallery

    Scientists from NASA's Kepler mission have been busy recently. The team has announced the discovery of Kepler-22b, its first confirmed planet in the habitable zone of its solar system, 600 light ye...

  20. Discovery of Asbestos After Demolition is Underway

    EPA Pesticide Factsheets

    Asbestos National Emissions Standard for Hazardous Air Pollutants Applicability Determination about additional friable asbestos material that arises during renovation or demolition being subject to the regulations from the time of creation or discovery

  1. Behind the Scenes: Discovery Crew Practices Landing

    NASA Video Gallery

    In this episode of NASA Behind the Scenes, Astronaut Mike Massimino introduces you to Commander Steve Lindsey and the crewmembers of STS-133, space shuttle Discovery's last mission. Go inside one o...

  2. Teaching Biochemistry in a "Guided Discovery Curriculum".

    ERIC Educational Resources Information Center

    Surlekar, Sheela

    1998-01-01

    Describes the implementation of the innovative Guided Discovery Curriculum at the National College of Chiropractic. Emphasizes the relevance of biochemical principles to clinical practice through the selection of two clinical cases. (DDR)

  3. Current Discoveries and Interventions for Barlow's Disease.

    PubMed

    Siordia, Juan A

    2016-08-01

    Mitral valve prolapse is a common valve pathology. One particular type of mitral valve prolapse that can be difficult to treat is Barlow's disease. This review serves to give insight on the current discoveries and therapeutic interventions of Barlow's disease.

  4. 43 CFR 4.826 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Special Procedural Rules Applicable to Practice and Procedure for Hearings, Decisions, and Administrative... the Interior-Effectuation of Title VI of the Civil Rights Act of 1964 Procedures § 4.826 Discovery....

  5. Priority of discovery in the life sciences

    PubMed Central

    Vale, Ronald D; Hyman, Anthony A

    2016-01-01

    The job of a scientist is to make a discovery and then communicate this new knowledge to others. For a scientist to be successful, he or she needs to be able to claim credit or priority for discoveries throughout their career. However, despite being fundamental to the reward system of science, the principles for establishing the "priority of discovery" are rarely discussed. Here we break down priority into two steps: disclosure, in which the discovery is released to the world-wide community; and validation, in which other scientists assess the accuracy, quality and importance of the work. Currently, in biology, disclosure and an initial validation are combined in a journal publication. Here, we discuss the advantages of separating these steps into disclosure via a preprint, and validation via a combination of peer review at a journal and additional evaluation by the wider scientific community. PMID:27310529

  6. Discovery Takes Off on New Mission

    NASA Video Gallery

    Space shuttle Discovery began its next mission April 17, 2012, when it took off from its operational home and headed to the Smithsonian Institution where it will be put on display to inspire the pu...

  7. Discovery announced of four new elements

    NASA Astrophysics Data System (ADS)

    Banks, Michael

    2016-02-01

    The International Union of Pure and Applied Chemistry (IUPAC) and the International Union of Pure and Applied Physics (IUPAP) have announced the discovery of four new elements: 113, 115, 117 and 118 - completing the periodic table's seventh row.

  8. 15 CFR 904.240 - Discovery generally.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the materials by other means. Mental impressions, conclusions, opinions, or legal theories of an... concerning discovery, the Judge may, in the interest of justice: (1) Infer that the admission,...

  9. 45 CFR 150.435 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AND INDIVIDUAL INSURANCE MARKETS Administrative Hearings § 150.435 Discovery. (a) The parties must.... The ALJ orders interrogatories or depositions only if these are the only means to develop the...

  10. Discovery's Last Launch a Spectacular Sight

    NASA Video Gallery

    Space shuttle Discovery lifted off at 4:53 p.m. EST Thursday from NASA's Kennedy Space Center in Florida, with Commander Steve Lindsey leading the STS-133 crew to deliver the Permanent Multipurpose...

  11. Arthritis Genetics Analysis Aids Drug Discovery

    MedlinePlus

    ... Matters NIH Research Matters January 13, 2014 Arthritis Genetics Analysis Aids Drug Discovery An international research team ... may play a role in triggering the disease. Genetic factors are also thought to play a role. ...

  12. Advances in synthetic peptides reagent discovery

    NASA Astrophysics Data System (ADS)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Stratis-Cullum, Dimitra N.

    2013-05-01

    Bacterial display technology offers a number of advantages over competing display technologies (e.g, phage) for the rapid discovery and development of peptides with interaction targeted to materials ranging from biological hazards through inorganic metals. We have previously shown that discovery of synthetic peptide reagents utilizing bacterial display technology is relatively simple and rapid to make laboratory automation possible. This included extensive study of the protective antigen system of Bacillus anthracis, including development of discovery, characterization, and computational biology capabilities for in-silico optimization. Although the benefits towards CBD goals are evident, the impact is far-reaching due to our ability to understand and harness peptide interactions that are ultimately extendable to the hybrid biomaterials of the future. In this paper, we describe advances in peptide discovery including, new target systems (e.g. non-biological materials), advanced library development and clone analysis including integrated reporting.

  13. 37 CFR 11.52 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., conclusions, opinions, or legal theories of any attorney or other representative of a party. (c) The hearing... the discovery sought; or (3) Consists of information that is available: (i) Generally to the...

  14. 37 CFR 11.52 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., conclusions, opinions, or legal theories of any attorney or other representative of a party. (c) The hearing... the discovery sought; or (3) Consists of information that is available: (i) Generally to the...

  15. 37 CFR 11.52 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., conclusions, opinions, or legal theories of any attorney or other representative of a party. (c) The hearing... the discovery sought; or (3) Consists of information that is available: (i) Generally to the...

  16. 20 CFR 355.21 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and §§ 355.22 and 355.23... creation of a document. (c) Unless mutually agreed to by the parties, discovery is available only...

  17. 49 CFR 31.21 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... relevant fact; (3) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and... require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...

  18. 29 CFR 22.21 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and §§ 22.22 and 22.23... creation of a document. (c) Unless mutually agreed to by the parties, discovery is available only...

  19. 41 CFR 105-70.021 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and §§ 105-70.022 and... the creation of a document. (c) Unless mutually agreed to by the parties, discovery is available...

  20. 12 CFR 308.520 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and §§ 308.521 and 308... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery...

  1. 41 CFR 105-70.021 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and §§ 105-70.022 and... the creation of a document. (c) Unless mutually agreed to by the parties, discovery is available...

  2. 41 CFR 105-70.021 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and §§ 105-70.022 and... the creation of a document. (c) Unless mutually agreed to by the parties, discovery is available...

  3. 29 CFR 22.21 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and §§ 22.22 and 22.23... creation of a document. (c) Unless mutually agreed to by the parties, discovery is available only...

  4. 34 CFR 33.21 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... relevant fact. (3) Written interrogatories. (4) Depositions. (b) For the purpose of this section and §§ 33... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery...

  5. 22 CFR 521.21 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of any relevant fact; (3) Written interrogatories; and (4) Depositions. (b) For the purpose of this... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery...

  6. 22 CFR 521.21 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... of any relevant fact; (3) Written interrogatories; and (4) Depositions. (b) For the purpose of this... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery...

  7. 22 CFR 521.21 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of any relevant fact; (3) Written interrogatories; and (4) Depositions. (b) For the purpose of this... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery...

  8. 29 CFR 22.21 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and §§ 22.22 and 22.23... creation of a document. (c) Unless mutually agreed to by the parties, discovery is available only...

  9. 20 CFR 355.21 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Written interrogatories; and (4) Depositions. (b) For the purpose of this section and §§ 355.22 and 355.23... creation of a document. (c) Unless mutually agreed to by the parties, discovery is available only...

  10. Radiation Detection Material Discovery Initiative at PNNL

    NASA Astrophysics Data System (ADS)

    Milbrath, Brian

    2006-05-01

    Today's security threats are being met with 30-year old radiation technology. Discovery of new radiation detection materials is currently a slow and Edisonian process. With heightened concerns over nuclear proliferation, terrorism and unconventional warfare, an alternative strategy for identification and development of potential radiation detection materials must be adopted. Through the Radiation Detection Materials Discovery Initiative, PNNL focuses on the science-based discovery of next generation materials for radiation detection by addressing three ``grand challenges'': fundamental understanding of radiation detection, identification of new materials, and accelerating the discovery process. The new initiative has eight projects addressing these challenges, which will be described, including early work, paths forward and the opportunities for collaboration.

  11. Evolving medicinal chemistry strategies in antibiotic discovery.

    PubMed

    Pawlowski, Andrew C; Johnson, Jarrod W; Wright, Gerard D

    2016-12-01

    Chemical modification of synthetic or natural product antibiotic scaffolds to expand potency and spectrum and to bypass mechanisms of resistance has dominated antibiotic drug discovery and proven immensely successful. However, the inexorable evolution of drug resistance coupled with a drought in innovation in antibiotic discovery contribute to a dearth of new drugs entering to market. Better understanding of the physicochemical properties of antibiotic chemical space is required to inform new antibiotic discovery. Innovations such as the development of antibiotic adjuvants to preserve efficacy of existing drugs together with expanding antibiotic chemical diversity through synthetic biology or new techniques to mine antibiotic producing organisms, are required to bridge the growing gap between the need for new drugs and their discovery.

  12. Advancing drug discovery: a pharmaceutics perspective.

    PubMed

    Kwong, Elizabeth

    2015-03-01

    Current industry perspective of how discovery is conducted seems to be fragmented and does not have a unified overall outlook of how discovery challenges are being addressed. Consequently, well-defined processes and drug-likeness criteria are being viewed as "broken" and will not maintain future R&D productivity. In this commentary, an analysis of existing practices for defining successful development candidates resulted in a 5 "must do" list to help advance Drug Discovery as presented from a Pharmaceutics perspective. The 5 "must do" list includes: what an ideal discovery team model should look like, what criteria should be considered for the desired development candidate profile, what the building blocks of the development candidate should look like, and how to assess the development risks of the candidate.

  13. 37 CFR 11.52 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., conclusions, opinions, or legal theories of any attorney or other representative of a party. (c) The hearing... the discovery sought; or (3) Consists of information that is available: (i) Generally to the...

  14. From Antarctica Lidar Discoveries to Oasis Exploration

    NASA Astrophysics Data System (ADS)

    Chu, Xinzhao; Yu, Zhibin; Fong, Weichun; Chen, Cao; Zhao, Jian; Barry, Ian F.; Smith, John A.; Lu, Xian; Huang, Wentao; Gardner, Chester S.

    2016-06-01

    Stunning new science discoveries including neutral thermospheric metal layers in the 100-200 km altitude from McMurdo lidar campaign and other world lidar observations have led to a new initiative in the middle and upper atmosphere science community—the very large-aperture lidar Observatory for Atmosphere Space Interaction Studies (OASIS). These discoveries and the recent technology breakthroughs in Fe and Na Doppler lidars are presented to illustrate the science drivers and technology foundations forming the basis for OASIS.

  15. Knowledge discovery of multilevel protein motifs

    SciTech Connect

    Conklin, D.; Glasgow, J.; Fortier, S.

    1994-12-31

    A new category of protein motif is introduced. This type of motif captures, in addition to global structure, the nested structure of its component parts. A dataset of four proteins is represented using this scheme. A structured machine discovery procedure is used to discover recurrent amino acid motifs and this knowledge is utilized for the expression of subsequent protein motif discoveries. Examples of discovered multilevel motifs are presented.

  16. Compound Data Mining for Drug Discovery.

    PubMed

    Bajorath, Jürgen

    2017-01-01

    In recent years, there has been unprecedented growth in compound activity data in the public domain. These compound data provide an indispensable resource for drug discovery in academic environments as well as in the pharmaceutical industry. To handle large volumes of heterogeneous and complex compound data and extract discovery-relevant knowledge from these data, advanced computational mining approaches are required. Herein, major public compound data repositories are introduced, data confidence criteria reviewed, and selected data mining approaches discussed.

  17. A d-Amino Acid-Containing Neuropeptide Discovery Funnel

    PubMed Central

    2016-01-01

    A receptor binding class of d-amino acid-containing peptides (DAACPs) is formed in animals from an enzymatically mediated post-translational modification of ribosomally translated all-l-amino acid peptides. Although this modification can be required for biological actions, detecting it is challenging because DAACPs have the same mass as their all-l-amino acid counterparts. We developed a suite of mass spectrometry (MS) protocols for the nontargeted discovery of DAACPs and validated their effectiveness using neurons from Aplysia californica. The approach involves the following three steps, with each confirming and refining the hits found in the prior step. The first step is screening for peptides resistant to digestion by aminopeptidase M. The second verifies the presence of a chiral amino acid via acid hydrolysis in deuterium chloride, labeling with Marfey’s reagent, and liquid chromatography–mass spectrometry to determine the chirality of each amino acid. The third involves synthesizing the putative DAACPs and comparing them to the endogenous standards. Advantages of the method, the d-amino acid-containing neuropeptide discovery funnel, are that it is capable of detecting the d-form of any common chiral amino acid, and the first two steps do not require peptide standards. Using these protocols, we report that two peptides from the Aplysia achatin-like neuropeptide precursor exist as GdYFD and SdYADSKDEESNAALSDFA. Interestingly, GdYFD was bioactive in the Aplysia feeding and locomotor circuits but SdYADSKDEESNAALSDFA was not. The discovery funnel provides an effective means to characterize DAACPs in the nervous systems of animals in a nontargeted manner. PMID:27788334

  18. Anticoagulant factor V: factors affecting the integration of novel scientific discoveries into the broader framework.

    PubMed

    LaBonte, Michelle L

    2014-09-01

    Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework.

  19. Computational methods for a three-dimensional model of the petroleum-discovery process

    USGS Publications Warehouse

    Schuenemeyer, J.H.; Bawiec, W.J.; Drew, L.J.

    1980-01-01

    A discovery-process model devised by Drew, Schuenemeyer, and Root can be used to predict the amount of petroleum to be discovered in a basin from some future level of exploratory effort: the predictions are based on historical drilling and discovery data. Because marginal costs of discovery and production are a function of field size, the model can be used to make estimates of future discoveries within deposit size classes. The modeling approach is a geometric one in which the area searched is a function of the size and shape of the targets being sought. A high correlation is assumed between the surface-projection area of the fields and the volume of petroleum. To predict how much oil remains to be found, the area searched must be computed, and the basin size and discovery efficiency must be estimated. The basin is assumed to be explored randomly rather than by pattern drilling. The model may be used to compute independent estimates of future oil at different depth intervals for a play involving multiple producing horizons. We have written FORTRAN computer programs that are used with Drew, Schuenemeyer, and Root's model to merge the discovery and drilling information and perform the necessary computations to estimate undiscovered petroleum. These program may be modified easily for the estimation of remaining quantities of commodities other than petroleum. ?? 1980.

  20. The Role of Competition, Community, and Priority in the Discovery of the Tau Lepton

    NASA Astrophysics Data System (ADS)

    Swanner, Leandra

    2006-05-01

    In this paper, I examine the interactions between the scientific communities of Lawrence Berkeley National Laboratory (LBNL) and the Stanford Linear Accelerator Center (SLAC) in the discovery of the tau lepton by physicist Martin Perl between 1973-1977. Although the experiments responsible for the discovery of this new particle were part of a collaborative effort between SLAC and LBNL, Perl became known for his individual role in interpreting the data and was awarded the Nobel Prize in physics for his work in 1995. Drawing upon personal and professional papers from the SLAC Archives and History Office, the LBNL Archives and Records Office, and my discussions with the physicists involved in the discovery, I argue that the discovery of the tau lepton challenges many of the common generalizations regarding the practice of ``Big Science.'' Big Science has often been associated with a transformation in the life of the experimenter as individual autonomy was subsumed by a `factory' work style typified by teamwork on a massive scale. However, an examination of the discovery of the tau lepton reveals that physicists at SLAC worked in small research groups, enjoyed great scientific freedom, and maintained a direct and interactive role in shaping research. This study also illustrates how scientific ambition motivates decisions underlying priority and discovery, which is highlighted by Perl's rush to publicize his findings in order to establish priority.

  1. Successes in drug discovery and design.

    PubMed

    2004-04-01

    The Society for Medicines Research (SMR) held a one-day meeting on case histories in drug discovery on December 4, 2003, at the National Heart and Lung Institute in London. These meetings have been organized by the SMR biannually for many years, and this latest meeting proved extremely popular, attracting a capacity audience of more than 130 registrants. The purpose of these meetings is educational; they allow those interested in drug discovery to hear key learnings from recent successful drug discovery programs. There was no overall linking theme between the talks, other than each success story has led to the introduction of a new and improved product of therapeutic use. The drug discovery stories covered in the meeting were extremely varied and, put together, they emphasized that each successful story is unique and special. This meeting is also special for the SMR because it presents the "SMR Award for Drug Discovery" in recognition of outstanding achievement and contribution in the area. It should be remembered that drug discovery is an extremely risky business and an extremely costly and complicated process in which the success rate is, at best, low.

  2. STS-114: Discovery Post MMT Briefing

    NASA Technical Reports Server (NTRS)

    2005-01-01

    On flight day 13, Leroy Cain, STS-114 Ascent/Entry Flight Director, discusses the condition of the Space Shuttle Discovery, and the weather outlook for landing. He answers questions from the news media about his feelings about re-entry since the Columbia tragedy, possible new information during re-entry, critical moments in the Mission Control Room during landing, and differences between night landing and day landing. Footage of the Mission Control Room and a talk with Soichi Noguchi in orbit is shown. Also, footage of the truss structure of the International Space Station, Destiny Laboratory, crew cabin of Discovery, and the Orbiter Docking System linked up to forward docking port on Discovery is shown. Eileen Collins and Wendy Lawrence are shown in the flight deck of Discovery. Charles Camarda is also shown in the mid-deck. Downlink television from Discovery shows spacewalk choreographer Andy Thomas with Stephen Robinson and Soichi Noguchi preparing for depressurization and pre-breathing activities that will lead to the opening of the hatch. The installation of a replacement GPS antenna, images of the port wing of Discovery and Canadarm moving with the Orbital Boom Sensor System (OBSS) extension is shown.

  3. The Relation of Learners' Motivation with the Process of Collaborative Scientific Discovery Learning

    ERIC Educational Resources Information Center

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

    2009-01-01

    In this study, we investigated the influence of individual learners' motivation on the collaborative discovery learning process. In this we distinguished the motivation of the individual learners and had eye for the composition of groups, which could be homogeneous or heterogeneous in terms of motivation. The study involved 73 dyads of 10th-grade…

  4. A history of the DNA repair and mutagenesis field: The discovery of base excision repair.

    PubMed

    Friedberg, Errol C

    2016-01-01

    This article reviews the early history of the discovery of an DNA repair pathway designated as base excision repair (BER), since in contrast to the enzyme-catalyzed removal of damaged bases from DNA as nucleotides [called nucleotide excision repair (NER)], BER involves the removal of damaged or inappropriate bases, such as the presence of uracil instead of thymine, from DNA as free bases.

  5. An Azulene-Based Discovery Experiment: Challenging Students to Watch for the "False Assumption"

    ERIC Educational Resources Information Center

    Garner, Charles M.

    2005-01-01

    A discovery-based experiment is developed depending on a "false assumption" that the students mistakenly assume they know the structure of a reaction product and are forced to reconcile observations that are inconsistent with this assumption. This experiment involves the chemistry of azulenes, an interesting class of intensely colored aromatic…

  6. Herbaria are a major frontier for species discovery.

    PubMed

    Bebber, Daniel P; Carine, Mark A; Wood, John R I; Wortley, Alexandra H; Harris, David J; Prance, Ghillean T; Davidse, Gerrit; Paige, Jay; Pennington, Terry D; Robson, Norman K B; Scotland, Robert W

    2010-12-21

    Despite the importance of species discovery, the processes including collecting, recognizing, and describing new species are poorly understood. Data are presented for flowering plants, measuring quantitatively the lag between the date a specimen of a new species was collected for the first time and when it was subsequently described and published. The data from our sample of new species published between 1970 and 2010 show that only 16% were described within five years of being collected for the first time. The description of the remaining 84% involved much older specimens, with nearly one-quarter of new species descriptions involving specimens >50 y old. Extrapolation of these results suggest that, of the estimated 70,000 species still to be described, more than half already have been collected and are stored in herbaria. Effort, funding, and research focus should, therefore, be directed as much to examining extant herbarium material as collecting new material in the field.

  7. Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases

    PubMed Central

    2015-01-01

    We report the discovery of a series of new drug leads that have potent activity against Mycobacterium tuberculosis as well as against other bacteria, fungi, and a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug SQ109 (1), which has been reported to act by inhibiting a transporter called MmpL3, involved in cell wall biosynthesis. We show that 1 and the new compounds also target enzymes involved in menaquinone biosynthesis and electron transport, inhibiting respiration and ATP biosynthesis, and are uncouplers, collapsing the pH gradient and membrane potential used to power transporters. The result of such multitarget inhibition is potent inhibition of TB cell growth, as well as very low rates of spontaneous drug resistance. Several targets are absent in humans but are present in other bacteria, as well as in malaria parasites, whose growth is also inhibited. PMID:24568559

  8. 4 CFR 28.42 - Discovery procedures and protective orders.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Discovery procedures and protective orders. 28.42 Section 28.42 Accounts GOVERNMENT ACCOUNTABILITY OFFICE GENERAL PROCEDURES GOVERNMENT ACCOUNTABILITY OFFICE... ACCOUNTABILITY OFFICE Procedures Discovery § 28.42 Discovery procedures and protective orders. (a) Discovery...

  9. 16 CFR 1025.31 - General provisions governing discovery.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false General provisions governing discovery. 1025... FOR ADJUDICATIVE PROCEEDINGS Discovery, Compulsory Process § 1025.31 General provisions governing discovery. (a) Applicability. The discovery rules established in this subpart are applicable to...

  10. 49 CFR 511.31 - General provisions governing discovery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 6 2013-10-01 2013-10-01 false General provisions governing discovery. 511.31... TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ADJUDICATIVE PROCEDURES Discovery; Compulsory Process § 511.31 General provisions governing discovery. (a) Applicability. The discovery...

  11. 49 CFR 511.31 - General provisions governing discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Discovery methods. Parties may obtain discovery by one or more of the following methods: (1) Written... section, the frequency of use of these methods is not limited. (c) Scope of discovery. The scope of... of or for litigation. Such discovery may be had by any of the methods provided in paragraph (b)...

  12. 5 CFR 1201.71 - Purpose of discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... party's case. These regulations are intended to provide a simple method of discovery. They will be... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Purpose of discovery. 1201.71 Section... AND PROCEDURES Procedures for Appellate Cases Discovery § 1201.71 Purpose of discovery....

  13. 17 CFR 12.30 - Methods of discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Methods of discovery. 12.30... REPARATIONS Discovery § 12.30 Methods of discovery. (a) In general. Parties may obtain discovery by the following methods in accordance with the procedures and limitations set forth in the section indicated:...

  14. 49 CFR 511.31 - General provisions governing discovery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... reasonably calculated to lead to the discovery of admissible evidence. (2) Exception. Parties may not obtain... Federal Rules of Civil Procedure. (3) Hearing preparation: Experts. A party may obtain discovery of facts... fact that a party is conducting discovery shall not operate to delay any other party's discovery....

  15. 49 CFR 511.31 - General provisions governing discovery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... reasonably calculated to lead to the discovery of admissible evidence. (2) Exception. Parties may not obtain... Federal Rules of Civil Procedure. (3) Hearing preparation: Experts. A party may obtain discovery of facts... fact that a party is conducting discovery shall not operate to delay any other party's discovery....

  16. History to the discovery of ghrelin.

    PubMed

    Bowers, Cyril Y

    2012-01-01

    The most important initial historical time points in the development of the enlarging ghrelin system were 1973, 1976, 1982, 1984, 1990, 1996, 1998, and 1999. At these respective times, the following occurred sequentially: isolation of somatostatin, discovery of unnatural growth-hormone-releasing peptides (GHRPs), isolation of growth-hormone-releasing hormone (GHRH), hypothesis of a new natural GHRP different from GHRH, GHRP+GHRH synergism in humans, discovery of the growth hormone secretagogue GHS/GHRP receptor, cloning of the receptor, and finally, isolation and identification of the new natural endogenous GHRP ghrelin. To understand the pharmacology and probably also the physiological regulation of growth hormone (GH) secretion, an important finding was that GHRP increased pulsatile GH secretion in children as well as normal younger and older men and women. This requires endogenous GHRH secretion, even though GHRP alone substantially releases GH from the pituitary in vitro without the addition of GHRH. Unnatural GHRP gave rise to natural GHRP ghrelin because of many talented researchers worldwide. GHRP was first envisioned to be an analog of GHRH but, from comparison of the activity of GHRH and GHRPs between 1982 and1984, it was hypothesized to reflect the activity of a new hormone regulator of GH secretion yet to be isolated and identified. Intravenous bolus GHRP releases more GH than GHRH in humans, but the reverse occurs in vitro. GHRPs are pleiotropic peptides with major effects on GH, nutrition, and metabolism, especially as an additional hormone in combination with GHRH as a new regulator of pulsatile GH secretion. The first indication of pleiotropism was an increase of food intake by GHRP. A major reason for the prolonged initial interest in the GHRPs has been its similar, yet different and complementary, action with GHRH on GH regulation and secretion. Particularly noteworthy is the variable chemistry of the GHRPs. They consist of three major chemical

  17. Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans.

    PubMed Central

    Mitchell, T G; Perfect, J R

    1995-01-01

    Although Cryptococcus neoformans and cryptococcosis have existed for several millennia, a century has passed since the discovery of this encapsulated yeast and its devastating disease. With the advent of the AIDS pandemic, cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality and a frequently life-threatening opportunistic mycosis among patients with AIDS. Both basic and clinical research have accelerated in the 1990s, and this review attempts to highlight some of these advances. The discussion covers recent findings, current concepts, controversies, and unresolved issues related to the ecology and genetics of C. neoformans; the surface structure of the yeast; and the mechanisms of host defense. Regarding cell-mediated immunity, CD4+ T cells are crucial for successful resistance, but CD8+ T cells may also participate significantly in the cytokine-mediated activation of anticryptococcal effector cells. In addition to cell-mediated immunity, monoclonal antibodies to the major capsular polysaccharide, the glucuronoxylomannan, offer some protection in murine models of cryptococcosis. Clinical concepts are presented that relate to the distinctive features of cryptococcosis in patients with AIDS and the diagnosis, treatment, and prevention of cryptococcosis in AIDS patients. PMID:8665468

  18. Impediments to Data Discovery in a Distributed Environment: A Workshop Report

    NASA Astrophysics Data System (ADS)

    Cornillon, P.

    2006-12-01

    Data discovery is often compartmentalized into discovery at the "catalog" level - high level, broad descriptions of data sets or collections - and discovery at the "inventory" level - detailed listings of granules in data sets. The catalog and inventory levels are also generally viewed as distinct from the data level, where the actual data granules reside. With an increase in on-line access to data such as that offered by OPeNDAP, WFS, WCS and WMS, there has been an increase in interest in discovery capabilities that provide the data, or lists of URLs for the data, meeting a variety of search criteria - in other words, a seamless capability to find and retrieve data of interest. In order to address issues related to discovery in a distributed environment, a workshop was held in May 2006 at Unidata/UCAR in Boulder, Colorado. Participants were drawn from 8 organizations dealing with various issues related to data discovery. The workshop began with the description of a number of different data discovery capabilities, including ECHO, GCMD, THREDDS, and ADL. This was followed by the analysis of two case studies with specific attention given to the ability, or lack thereof, of current data discovery components to find data relevant to the case studies. Several key findings resulted from this analysis which, although obvious in retrospect, we believe to be major deficiencies in the way data discovery is being approached today. These findings are: There is no consistency in the inventorying of data. Links between the catalog, inventory and data levels are tenuous at best; moving from the catalog to the inventory level and from the inventory to the data level is tedious at best. There is little to no consistency in the access protocols that are used by data discovery components. This is especially true at the inventory level. These findings suggest that the level of effort involved in finding data of interest could be substantially reduced by either reducing the number of

  19. Choosing Discovery: A Literature Review on the Selection and Evaluation of Discovery Layers

    ERIC Educational Resources Information Center

    Moore, Kate B.; Greene, Courtney

    2012-01-01

    Within the next few years, traditional online public access catalogs will be replaced by more robust and interconnected discovery layers that can serve as primary public interfaces to simultaneously search many separate collections of resources. Librarians have envisioned this type of discovery tool since the 1980s, and research shows that…

  20. What Does Galileo's Discovery of Jupiter's Moons Tell Us about the Process of Scientific Discovery?

    ERIC Educational Resources Information Center

    Lawson, Anton E.

    2002-01-01

    Given that hypothetico-deductive reasoning has played a role in other important scientific discoveries, asks the question whether it plays a role in all important scientific discoveries. Explores and rejects as viable alternatives possible alternative scientific methods such as Baconian induction and combinatorial analysis. Discusses the…

  1. Involving LEP Parents.

    ERIC Educational Resources Information Center

    Garate, Dama; And Others

    Four community liaisons for public school programs for limited- English-proficient (LEP) populations discuss briefly aspects of parent involvement. Dama Garate describes the populations served by the Trinity-Arlington Project in the Arlington (Virginia) Public Schools and suggests issues to be considered in parent involvement efforts. Pirun Sen of…

  2. High Involvement Work Teams.

    ERIC Educational Resources Information Center

    1996

    These three papers were presented at a symposium on high-involvement work teams moderated by Michael Leimbach at the 1996 conference of the Academy of Human Resource Development. "Beyond Training to the New Learning Environment: Workers on the High-Involvement Frontline" (Joseph Anthony Ilacqua, Carol Ann Zulauf) shows the link between…

  3. [Families Involved in Learning.

    ERIC Educational Resources Information Center

    Ashby, Nicole, Ed.

    2001-01-01

    This issue of "Community Update" focuses on families involved in learning. The first article briefly discusses the "Ready to Read, Ready to Learn" White House summit that highlighted new research on early childhood learning. The center spread of this issue offers "Priming the Primary Educator: A Look at L. A. County's Parent Involvement Programs"…

  4. Categories of Parent Involvement.

    ERIC Educational Resources Information Center

    Bauch, Jerold P.

    1994-01-01

    The growing interest in effective parent involvement has produced several ways to classify or describe ways parents are or should be involved. This article reviews and evaluates Ira Gordon's systems approach, the California-based System Development Corporation's categories, Eugenia H. Berger's parental role categories, Chavkin and Williams' parent…

  5. Commericial Involvement in Intramurals.

    ERIC Educational Resources Information Center

    Maas, Gerry

    Sport in general has long had ties with commercial interests, the most popular and widespread involving publicity. Intramural sports programs, however, have not cultivated many commercial involvements in publicity. The approach in intramural sports advertising is simple. A commercial interest pays for space or time in a given communication media…

  6. ADS Services in support of the Discovery, Management and Evaluation of Science Data

    NASA Astrophysics Data System (ADS)

    Accomazzi, Alberto

    2015-12-01

    The NASA Astrophysics Data System (ADS) has long been used as a discovery platform for the scientific literature in Astronomy and Physics. With the addition of records describing datasets linked to publications, observing proposals and software used in refereed astronomy papers, the ADS is now increasingly used to find, access and cite an wider number of scientific resources. In this talk, I will discuss the recent efforts involving the indexing of software metadata, and our ongoing discussions with publishers in support of software and data citation. I will demonstrate the use of ADS's new services in support of discovery and evaluation of individual researchers as well as archival data products.

  7. BCL-2: Long and winding path from discovery to therapeutic target.

    PubMed

    Schenk, Robyn L; Strasser, Andreas; Dewson, Grant

    2017-01-15

    In 1988, the BCL-2 protein was found to promote cancer by limiting cell death rather than enhancing proliferation. This discovery set the wheels in motion for an almost 30 year journey involving many international research teams that has recently culminated in the approval for a drug, ABT-199/venetoclax/Venclexta that targets this protein in the treatment of cancer. This review will describe the long and winding path from the discovery of this protein and understanding the fundamental process of apoptosis that BCL-2 and its numerous homologues control, through to its exploitation as a drug target that is set to have significant benefit for cancer patients.

  8. The chemistry-biology-medicine continuum and the drug discovery and development process in academia.

    PubMed

    Nicolaou, K C

    2014-09-18

    Admirable as it is, the drug discovery and development process is continuously undergoing changes and adjustments in search of further improvements in efficiency, productivity, and profitability. Recent trends in academic-industrial partnerships promise to provide new opportunities for advancements of this process through transdisciplinary collaborations along the entire spectrum of activities involved in this complex process. This perspective discusses ways to promote the emerging academic paradigm of the chemistry-biology-medicine continuum as a means to advance the drug discovery and development process.

  9. New Discoveries of Sylvatic Triatoma infestans (Hemiptera: Reduviidae) Throughout the Bolivian Chaco

    PubMed Central

    Waleckx, Etienne; Depickère, Stéphanie; Salas, Renata; Aliaga, Claudia; Monje, Marcelo; Calle, Hiber; Buitrago, Rosio; Noireau, François; Brenière, Simone Frédérique

    2012-01-01

    Sylvatic populations of Triatoma infestans might be involved in the recolonization of human dwellings. We report here the discoveries of new T. infestans sylvatic foci in the Bolivian Chaco. Eighty-one triatomines were caught, 38 of which were identified as T. infestans. Triatoma sordida and Panstrongylus geniculatus were the other species collected. One T. infestans and one T. sordida were infected with Trypanosoma cruzi TcI; one T. infestans was infected with TcII. These discoveries add to the debate on the geographic distribution of sylvatic T. infestans populations, the geographic origin of the species, and the epidemiological role of these populations. PMID:22403316

  10. Predicting future discoveries from current scientific literature.

    PubMed

    Petrič, Ingrid; Cestnik, Bojan

    2014-01-01

    Knowledge discovery in biomedicine is a time-consuming process starting from the basic research, through preclinical testing, towards possible clinical applications. Crossing of conceptual boundaries is often needed for groundbreaking biomedical research that generates highly inventive discoveries. We demonstrate the ability of a creative literature mining method to advance valuable new discoveries based on rare ideas from existing literature. When emerging ideas from scientific literature are put together as fragments of knowledge in a systematic way, they may lead to original, sometimes surprising, research findings. If enough scientific evidence is already published for the association of such findings, they can be considered as scientific hypotheses. In this chapter, we describe a method for the computer-aided generation of such hypotheses based on the existing scientific literature. Our literature-based discovery of NF-kappaB with its possible connections to autism was recently approved by scientific community, which confirms the ability of our literature mining methodology to accelerate future discoveries based on rare ideas from existing literature.

  11. Lifeomics leads the age of grand discoveries.

    PubMed

    He, Fuchu

    2013-03-01

    When our knowledge of a field accumulates to a certain level, we are bound to see the rise of one or more great scientists. They will make a series of grand discoveries/breakthroughs and push the discipline into an 'age of grand discoveries'. Mathematics, geography, physics and chemistry have all experienced their ages of grand discoveries; and in life sciences, the age of grand discoveries has appeared countless times since the 16th century. Thanks to the ever-changing development of molecular biology over the past 50 years, contemporary life science is once again approaching its breaking point and the trigger for this is most likely to be 'lifeomics'. At the end of the 20th century, genomics wrote out the 'script of life'; proteomics decoded the script; and RNAomics, glycomics and metabolomics came into bloom. These 'omics', with their unique epistemology and methodology, quickly became the thrust of life sciences, pushing the discipline to new high. Lifeomics, which encompasses all omics, has taken shape and is now signalling the dawn of a new era, the age of grand discoveries.

  12. False discovery rates: a new deal

    PubMed Central

    2017-01-01

    Summary We introduce a new Empirical Bayes approach for large-scale hypothesis testing, including estimating false discovery rates (FDRs), and effect sizes. This approach has two key differences from existing approaches to FDR analysis. First, it assumes that the distribution of the actual (unobserved) effects is unimodal, with a mode at 0. This “unimodal assumption” (UA), although natural in many contexts, is not usually incorporated into standard FDR analysis, and we demonstrate how incorporating it brings many benefits. Specifically, the UA facilitates efficient and robust computation—estimating the unimodal distribution involves solving a simple convex optimization problem—and enables more accurate inferences provided that it holds. Second, the method takes as its input two numbers for each test (an effect size estimate and corresponding standard error), rather than the one number usually used (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$p$\\end{document} value or \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$z$\\end{document} score). When available, using two numbers instead of one helps account for variation in measurement precision across tests. It also facilitates estimation of effects, and unlike standard FDR methods, our approach provides interval estimates (credible regions) for each effect in addition to measures of significance. To provide a bridge between interval estimates and significance measures, we introduce the term “local false sign rate” to refer to the probability of getting the sign of an effect wrong and argue that it is a superior

  13. Drosophila and Caenorhabditis elegans as Discovery Platforms for Genes Involved in Human Alcohol Use Disorder

    PubMed Central

    Grotewiel, Mike; Bettinger, Jill C.

    2015-01-01

    Background Despite the profound clinical significance and strong heritability of alcohol use disorder (AUD), we do not yet have a comprehensive understanding of the naturally occurring genetic variance within the human genome that drives its development. This lack of understanding is likely to be due in part to the large phenotypic and genetic heterogeneities that underlie human AUD. As a complement to genetic studies in humans, many laboratories are using the invertebrate model organisms (iMOs) Drosophila melanogaster (fruit fly) and Caenorhabditis elegans (nematode worm) to identify genetic mechanisms that influence the effects of alcohol (ethanol) on behavior. While these extremely powerful models have identified many genes that influence the behavioral responses to alcohol, in most cases it has remained unclear whether results from behavioral–genetic studies in iMOs are directly applicable to understanding the genetic basis of human AUD. Methods In this review, we critically evaluate the utility of the fly and worm models for identifying genes that influence AUD in humans. Results Based on results published through early 2015, studies in flies and worms have identified 91 and 50 genes, respectively, that influence 1 or more aspects of behavioral responses to alcohol. Collectively, these fly and worm genes correspond to 293 orthologous genes in humans. Intriguingly, 51 of these 293 human genes have been implicated in AUD by at least 1 study in human populations. Conclusions Our analyses strongly suggest that the Drosophila and C. elegans models have considerable utility for identifying orthologs of genes that influence human AUD. PMID:26173477

  14. Protein chemical synthesis in drug discovery.

    PubMed

    Liu, Fa; Mayer, John P

    2015-01-01

    The discovery of novel therapeutics to combat human disease has traditionally been among the most important goals of research chemists. After a century of innovation, state-of-the-art chemical protein synthesis is now capable of efficiently assembling proteins of up to several hundred residues in length from individual amino acids. By virtue of its unique ability to incorporate non-native structural elements, chemical protein synthesis has been seminal in the recent development of several novel drug discovery technologies. In this chapter, we review the key advances in peptide and protein chemistry which have enabled our current synthetic capabilities. We also discuss the synthesis of D-proteins and their applications in mirror image phage-display and racemic protein crystallography, the synthesis of enzymes for structure-based drug discovery, and the direct synthesis of homogenous protein pharmaceuticals.

  15. Bioanalysis in drug discovery and development

    PubMed Central

    Pandey, Saurabh; Pandey, Preeti; Tiwari, Gaurav; Tiwari, Ruchi

    2010-01-01

    Recent years have witnessed the introduction of several high-quality review articles into the literature covering various scientific and technical aspects of bioanalysis. Now it is widely accepted that bioanalysis is an integral part of the pharmacokinetic/pharmacodynamic characterization of a novel chemical entity from the time of its discovery and during various stages of drug development, leading to its market authorization. In this compilation, the important bioanalytical parameters and its application to drug discovery and development approaches are discussed, which will help in the development of safe and more efficacious drugs with reduced development time and cost. It is intended to give some general thoughts in this area which will form basis of a general framework as to how one would approach bioanalysis from inception (i.e., discovery of a lead molecule) and progressing through various stages of drug development. PMID:23781412

  16. Phosphoproteome Discovery in Human Biological Fluids

    PubMed Central

    Giorgianni, Francesco; Beranova-Giorgianni, Sarka

    2016-01-01

    Phosphorylation plays a critical role in regulating protein function and thus influences a vast spectrum of cellular processes. With the advent of modern bioanalytical technologies, examination of protein phosphorylation on a global scale has become one of the major research areas. Phosphoproteins are found in biological fluids and interrogation of the phosphoproteome in biological fluids presents an exciting opportunity for discoveries that hold great potential for novel mechanistic insights into protein function in health and disease, and for translation to improved diagnostic and therapeutic approaches for the clinical setting. This review focuses on phosphoproteome discovery in selected human biological fluids: serum/plasma, urine, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. Bioanalytical workflows pertinent to phosphoproteomics of biological fluids are discussed with emphasis on mass spectrometry-based approaches, and summaries of studies on phosphoproteome discovery in major fluids are presented. PMID:28248247

  17. Antifungal drug discovery: the process and outcomes

    PubMed Central

    Calderone, Richard; Sun, Nuo; Gay-Andrieu, Francoise; Groutas, William; Weerawarna, Pathum; Prasad, Sridhar; Alex, Deepu; Li, Dongmei

    2014-01-01

    New data suggest that the global incidence of several types of fungal diseases have traditionally been under-documented. Of these, mortality caused by invasive fungal infections remains disturbingly high, equal to or exceeding deaths caused by drug-resistant tuberculosis and malaria. It is clear that basic research on new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we focus upon antifungal drug discovery including in vitro assays, compound libraries and approaches to target identification. Genome mining has made it possible to identify fungal-specific targets; however, new compounds to these targets are apparently not in the antimicrobial pipeline. We suggest that ‘repurposing’ compounds (off patent) might be a more immediate starting point. Furthermore, we examine the dogma on antifungal discovery and suggest that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery. PMID:25046525

  18. Computational approaches to natural product discovery

    PubMed Central

    Medema, Marnix H.; Fischbach, Michael A.

    2016-01-01

    From the earliest Streptomyces genome sequences, the promise of natural product genome mining has been captivating: genomics and bioinformatics would transform compound discovery from an ad hoc pursuit to a high-throughput endeavor. Until recently, however, genome mining has advanced natural product discovery only modestly. Here, we argue that the development of algorithms to mine the continuously increasing amounts of (meta)genomic data will enable the promise of genome mining to be realized. We review computational strategies that have been developed to identify biosynthetic gene clusters in genome sequences and predict the chemical structures of their products. We then discuss networking strategies that can systematize large volumes of genetic and chemical data, and connect genomic information to metabolomic and phenotypic data. Finally, we provide a vision of what natural product discovery might look like in the future, specifically considering long-standing questions in microbial ecology regarding the roles of metabolites in interspecies interactions. PMID:26284671

  19. STS-70 Discovery launch (thru palm trees)

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Against the verdant backdrop of a Florida summer in full bloom, the Space Shuttle Discovery climbs a ladder of fire reaching to the sky. Discovery lifted off on Mission STS-70 from Launch Pad 39B at 9:41:55:078 a.m. EDT. The 70th Shuttle flight overall is the 21st for Discovery (OV-103) and the fourth Shuttle flight in 1995. On board for the planned eight-day mission are a crew of five: Commander Terence 'Tom' Hendricks; Pilot Kevin R. Kregel; and Mission Specialists Nancy Jane Currie, Donald A. Thomas and Mary Ellen Weber. The crew's primary objective is to deploy the Tracking and Data Relay Satellite-G (TDRS-G), which will join a constellation of other TDRS spacecraft already on orbit.

  20. John Herschel on the Discovery of Neptune

    NASA Astrophysics Data System (ADS)

    Kollerstrom, Nicholas

    2006-12-01

    The letters of John Herschel that concern the discovery of the planet Neptune have not been greatly discussed by historians of science. I have transcribed these in the course of archiving the British Neptune-discovery documents. Herschel tends to be depicted as a background figure in narrations of the story of Neptune's discovery, whereas the present account focuses upon his evolving view of the topic: the rival merits of the two main protagonists, and the startling manner in which an obscure branch of mathematics (perturbation theory) was able to pinpoint the position of a new sphere in the sky. As the son of the man who found Uranus, his views have a special relevance. Also, I suggest that his eloquent prose style may still be enjoyed today.

  1. Pattern Discovery in Time-Ordered Data

    SciTech Connect

    CONRAD, GREGORY N.; BRITANIK, JOHN M.; DELAND, SHARON M.; JENKIN, CHRISTINA L.

    2002-02-01

    This report describes the results of a Laboratory-Directed Research and Development project on techniques for pattern discovery in discrete event time series data. In this project, we explored two different aspects of the pattern matching/discovery problem. The first aspect studied was the use of Dynamic Time Warping for pattern matching in continuous data. In essence, DTW is a technique for aligning time series along the time axis to optimize the similarity measure. The second aspect studied was techniques for discovering patterns in discrete event data. We developed a pattern discovery tool based on adaptations of the A-priori and GSP (Generalized Sequential Pattern mining) algorithms. We then used the tool on three different application areas--unattended monitoring system data from a storage magazine, computer network intrusion detection, and analysis of robot training data.

  2. Computational approaches to natural product discovery.

    PubMed

    Medema, Marnix H; Fischbach, Michael A

    2015-09-01

    Starting with the earliest Streptomyces genome sequences, the promise of natural product genome mining has been captivating: genomics and bioinformatics would transform compound discovery from an ad hoc pursuit to a high-throughput endeavor. Until recently, however, genome mining has advanced natural product discovery only modestly. Here, we argue that the development of algorithms to mine the continuously increasing amounts of (meta)genomic data will enable the promise of genome mining to be realized. We review computational strategies that have been developed to identify biosynthetic gene clusters in genome sequences and predict the chemical structures of their products. We then discuss networking strategies that can systematize large volumes of genetic and chemical data and connect genomic information to metabolomic and phenotypic data. Finally, we provide a vision of what natural product discovery might look like in the future, specifically considering longstanding questions in microbial ecology regarding the roles of metabolites in interspecies interactions.

  3. INTEGRATE: gene fusion discovery using whole genome and transcriptome data

    PubMed Central

    Zhang, Jin; White, Nicole M.; Schmidt, Heather K.; Fulton, Robert S.; Tomlinson, Chad; Warren, Wesley C.; Wilson, Richard K.; Maher, Christopher A.

    2016-01-01

    While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use. PMID:26556708

  4. Animal models in the drug discovery pipeline for Alzheimer's disease

    PubMed Central

    Van Dam, Debby; De Deyn, Peter Paul

    2011-01-01

    With increasing feasibility of predicting conversion of mild cognitive impairment to dementia based on biomarker profiling, the urgent need for efficacious disease-modifying compounds has become even more critical. Despite intensive research, underlying pathophysiological mechanisms remain insufficiently documented for purposeful target discovery. Translational research based on valid animal models may aid in alleviating some of the unmet needs in the current Alzheimer's disease pharmaceutical market, which includes disease-modification, increased efficacy and safety, reduction of the number of treatment unresponsive patients and patient compliance. The development and phenotyping of animal models is indeed essential in Alzheimer's disease-related research as valid models enable the appraisal of early pathological processes – which are often not accessible in patients, and subsequent target discovery and evaluation. This review paper summarizes and critically evaluates currently available animal models, and discusses their value to the Alzheimer drug discovery pipeline. Models dealt with include spontaneous models in various species, including senescence-accelerated mice, chemical and lesion-induced rodent models, and genetically modified models developed in Drosophila melanogaster, Caenorhabditis elegans, Danio rerio and rodents. Although highly valid animal models exist, none of the currently available models recapitulates all aspects of human Alzheimer's disease, and one should always be aware of the potential dangers of uncritical extrapolating from model organisms to a human condition that takes decades to develop and mainly involves higher cognitive functions. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21371009

  5. The Rise of Computer-Aided Discovery in Geoscience

    NASA Astrophysics Data System (ADS)

    Pankratius, V.; Blair, D. M.; Gowanlock, M.; Lind, F. D.; Erickson, P. J.

    2015-12-01

    Next-generation Geoscience will need to handle rapidly growing data volumes and exploration of complex phenomena challenging human cognitive limits. With instruments digitizing large amounts of sensor data from many sources, the scientific discovery process becomes a large-scale search process. However, insight generation is still a key problem and is especially complex in Geoscience, particularly when exploratory studies involve fusion of large data from various instruments in a manual labor-intensive manner. We propose an approach for a computer-aided discovery infrastructure that automatically explores the connection between physics models and empirical data to accelerate the pace of new discoveries. The approach uses (1) A system engaging scientists to programmatically express hypothesized Geoscience scenarios, constraints, and model variations, so as to automatically explore and evaluate the combinatorial search space of possible explanations in parallel on a variety of data sets. This automated system employs machine learning to support algorithmic choice and workflow reconfiguration allowing systematic pruning of the search space of applied algorithms and parameters based on historical results. (2) A cloud-based environment allowing scientists to conduct powerful exploratory analyses on large data sets that reside in data centers. Various search modes are provided, including a mode where scientists can iteratively guide the search based on intermediate results. This functionality directs the system to identify more Geospace features that are analogous or related in various ways. (3) Scientist input is used to configure programmable crawlers that automate and scale the search for interesting phenomena on cloud-based infrastructures. We discuss various application scenarios to show the impact of workflow configuration on scientific feature detection. Acknowledgements. We acknowledge support from NSF ACI-1442997 and NASA AIST NNX15AG84G (PI: V. Pankratius).

  6. INTEGRATE: gene fusion discovery using whole genome and transcriptome data.

    PubMed

    Zhang, Jin; White, Nicole M; Schmidt, Heather K; Fulton, Robert S; Tomlinson, Chad; Warren, Wesley C; Wilson, Richard K; Maher, Christopher A

    2016-01-01

    While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use.

  7. The discovery of elements 113 to 118

    NASA Astrophysics Data System (ADS)

    Utyonkov, Vladimir; Oganessian, Yuri; Dmitriev, Sergey; Itkis, Mikhail; Moody, Kenton; Stoyer, Mark; Shaughnessy, Dawn; Roberto, James; Rykaczewski, Krzysztof; Hamilton, Joseph

    2016-12-01

    Discovery and investigation of the "Island of stability" of superheavy nuclei at the separator DGFRS in the 238U-249Cf+ 48Ca reactions is reviewed. The results are compared with the data obtained in chemistry experiments and at the separators SHIP, BGS, TASCA, and GARIS. The synthesis of the heaviest nuclei, their decay properties, and methods of identification are discussed and compared with the criteria that must be satisfied for claiming the discovery of a new chemical element. The role of shell effects in the stability of superheavy nuclei is demonstrated by comparison of the experimental results with empirical systematics and theoretical data.

  8. STS-114: Discovery Post Landing Press Briefing

    NASA Technical Reports Server (NTRS)

    2005-01-01

    A post landing discussion of the STS-114 Space Shuttle Discovery is shown. Dean Acosta, Deputy Assistant Administrator of Public Affairs introduces the panel. The panel consists of: Michael Griffin, NASA Administrator, Bill Parsons, Space Shuttle Program Manager, Mike Leinbach, NASA Launch Director, and Bill Readdy, Associate Administrator for Space Operations. Mike Griffin answers questions from the news media about the amount of damage to the Space Shuttle and the possibility of returning to space, Mike Leinbach addresses the question about the process of bringing Discovery back to Kennedy Space Center and Bill Parsons talks about milestones reached during this mission.

  9. STS-114: Discovery Post Landing Press Briefing

    NASA Technical Reports Server (NTRS)

    2005-01-01

    Dean Acosta, NASA Public Affairs Deputy Assistant Administrator hosted this press briefing. Michael Griffin, NASA Administrator; Bill Parsons, Shuttle Program Manager; Michael Leinbach, Shuttle Launch Director; and Bill Ready, Space Operations Associate Administrator were present. The Panel specifically honored the Columbia crew as they praised Commander Eileen Collin's performance in bringing the Discovery and crew safe back to Earth. Re-entry, test flight and next test flight, thermal insulation, heat, vehicle inspection, turn around processing, and ferrying Discovery back to the Kennedy Space Center were topics covered with the News media. Michael Griffin announced the launching of Mars Reconnaissance Orbiter will take place the following morning.

  10. Renaissance in antibacterial discovery from actinomycetes.

    PubMed

    Baltz, Richard H

    2008-10-01

    The soil actinomycetes have been important sources of antibiotics, but were nearly abandoned in recent years in favor of high-throughput target-based screening of chemical libraries. The latter approach has not been productive, so it is time to reinvigorate the discovery of new antibiotics from a proven source. Recent progress has been made on antibiotic discovery from actinomycetes by using high-throughput fermentation, isolation of marine actinomycetes, mining genomes for cryptic pathways, and combinatorial biosynthesis to generate new secondary metabolites related to existing pharmacophores.

  11. Marine actinomycete diversity and natural product discovery.

    PubMed

    Jensen, Paul R; Mincer, Tracy J; Williams, Philip G; Fenical, William

    2005-01-01

    Microbial natural products remain an important resource for drug discovery yet the microorganisms inhabiting the world's oceans have largely been overlooked in this regard. The recent discovery of novel secondary metabolites from taxonomically unique populations of marine actinomycetes suggests that these bacteria add an important new dimension to microbial natural product research. Continued efforts to characterize marine actinomycete diversity and how adaptations to the marine environment affect secondary metabolite production will create a better understanding of the potential utility of these bacteria as a source of useful products for biotechnology.

  12. Net present value approaches for drug discovery.

    PubMed

    Svennebring, Andreas M; Wikberg, Jarl Es

    2013-12-01

    Three dedicated approaches to the calculation of the risk-adjusted net present value (rNPV) in drug discovery projects under different assumptions are suggested. The probability of finding a candidate drug suitable for clinical development and the time to the initiation of the clinical development is assumed to be flexible in contrast to the previously used models. The rNPV of the post-discovery cash flows is calculated as the probability weighted average of the rNPV at each potential time of initiation of clinical development. Practical considerations how to set probability rates, in particular during the initiation and termination of a project is discussed.

  13. Antibacterial drug discovery in the resistance era.

    PubMed

    Brown, Eric D; Wright, Gerard D

    2016-01-21

    The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large. The evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens has made diseases that were once easily treatable deadly again. Unfortunately, accompanying the rise in global resistance is a failure in antibacterial drug discovery. Lessons from the history of antibiotic discovery and fresh understanding of antibiotic action and the cell biology of microorganisms have the potential to deliver twenty-first century medicines that are able to control infection in the resistance era.

  14. Discovery stories in the science classroom

    NASA Astrophysics Data System (ADS)

    Arya, Diana Jaleh

    School science has been criticized for its lack of emphasis on the tentative, dynamic nature of science as a process of learning more about our world. This criticism is the guiding force for this present body of work, which focuses on the question: what are the educational benefits for middle school students of reading texts that highlight the process of science in the form of a discovery narrative? This dissertation traces my journey through a review of theoretical perspectives of narrative, an analysis of first-hand accounts of scientific discovery, the complex process of developing age-appropriate, cohesive and engaging science texts for middle school students, and a comparison study (N=209) that seeks to determine the unique benefits of the scientific discovery narrative for the interest in and retained understanding of conceptual information presented in middle school science texts. A total of 209 middle school participants in nine different classrooms from two different schools participated in the experimental study. Each subject read two science texts that differed in topic (the qualities of and uses for radioactive elements and the use of telescopic technology to see planets in space) and genre (the discovery narrative and the "conceptually known exposition" comparison text). The differences between the SDN and CKE versions for each topic were equivalent in all possible ways (initial introduction, overall conceptual accuracy, elements of human interest, coherence and readability level), save for the unique components of the discovery narrative (i.e., love for their work, acknowledgement of the known, identification of the unknown and the explorative or experimental process to discovery). Participants generally chose the discovery narrative version as the more interesting of the two texts. Additional findings from the experimental study suggest that science texts in the form of SDNs elicit greater long-term retention of key conceptual information, especially

  15. An environment for knowledge discovery in biology.

    PubMed

    Barrera, Junior; Cesar, Roberto M; Ferreira, João E; Gubitoso, Marco D

    2004-07-01

    This paper describes a data mining environment for knowledge discovery in bioinformatics applications. The system has a generic kernel that implements the mining functions to be applied to input primary databases, with a warehouse architecture, of biomedical information. Both supervised and unsupervised classification can be implemented within the kernel and applied to data extracted from the primary database, with the results being suitably stored in a complex object database for knowledge discovery. The kernel also includes a specific high-performance library that allows designing and applying the mining functions in parallel machines. The experimental results obtained by the application of the kernel functions are reported.

  16. Cost efficient operations for Discovery class missions

    NASA Technical Reports Server (NTRS)

    Cameron, G. E.; Landshof, J. A.; Whitworth, G. W.

    1994-01-01

    The Near Earth Asteroid Rendezvous (NEAR) program at The Johns Hopkins University Applied Physics Laboratory is scheduled to launch the first spacecraft in NASA's Discovery program. The Discovery program is to promote low cost spacecraft design, development, and mission operations for planetary space missions. The authors describe the NEAR mission and discuss the design and development of the NEAR Mission Operations System and the NEAR Ground System with an emphasis on those aspects of the design that are conducive to low-cost operations.

  17. [Heart involvement in sarcoglycanopathies].

    PubMed

    Fayssoil, A; Nardi, O; Orlikowski, D; Annane, D

    2012-11-01

    Sarcoglycanopathies (SG) are autosomic recessive muscular dystrophies, secondary to mutations of the sarcoglycan complex. Clinical pictures include muscle weakness affecting mainly the proximal limb girdle musculature. We review heart involvement in this group of disease.

  18. Consumer Involvement in Rehabilitation

    ERIC Educational Resources Information Center

    Daniels, Susan

    1976-01-01

    With the emphasis on consumer involvement in the Rehabilitation Act of 1973, changes in the counseling relationship must occur. This article discusses new interaction patterns for consumer and counselor. (Author)

  19. The history of aerobic ammonia oxidizers: from the first discoveries to today.

    PubMed

    Monteiro, Maria; Séneca, Joana; Magalhães, Catarina

    2014-07-01

    Nitrification, the oxidation of ammonia to nitrite and nitrate, has long been considered a central biological process in the global nitrogen cycle, with its first description dated 133 years ago. Until 2005, bacteria were considered the only organisms capable of nitrification. However, the recent discovery of a chemoautotrophic ammonia-oxidizing archaeon, Nitrosopumilus maritimus, changed our concept of the range of organisms involved in nitrification, highlighting the importance of ammonia-oxidizing archaea (AOA) as potential players in global biogeochemical nitrogen transformations. The uniqueness of these archaea justified the creation of a novel archaeal phylum, Thaumarchaeota. These recent discoveries increased the global scientific interest within the microbial ecology society and have triggered an analysis of the importance of bacterial vs archaeal ammonia oxidation in a wide range of natural ecosystems. In this mini review we provide a chronological perspective of the current knowledge on the ammonia oxidation pathway of nitrification, based on the main physiological, ecological and genomic discoveries.

  20. Vasculitis and gastrointestinal involvement.

    PubMed

    Casella, G; Bronzino, B; Cutrino, L; Montani, N; Somma, A; Baldini, V

    2006-06-01

    The incidence of gastrointestinal involvement is relatively observed in patients with vasculitis processes. Vasculitis can be primary (necrotising or hypersensitivity) or secondary to another primary disease. Gastrointestinal involvement is present in up to 50% of the various forms of systemic vasculitis. Primary or secondary vasculitic process, according to the classification in necrotizing and hypersensitivity vasculitis, are described in this paper. A review of the literature on the the subject is also presented.