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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. Huanglongbing: a 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...

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

    PubMed

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

    2015-11-01

    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.

  4. 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

  5. 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. PMID:27325272

  6. Disclosure of misattributed paternity: issues involved in the discovery of unsought information.

    PubMed

    Wright, Linda; MacRae, Susan; Gordon, Debra; Elliot, Esther; Dixon, David; Abbey, Susan; Richardson, Robert

    2002-01-01

    Kidney transplantation from living donors is generally a safe, effective form of renal replacement therapy. When evaluating potential living donors and their intended recipients, a careful assessment process is followed in order to ensure that ethical standards are upheld. During this assessment, important medical information with serious consequences, which was not being sought as part of the donor/recipient evaluation, may be discovered. The information may or may not be relevant to the decision to donate. However, such a discovery raises the difficult questions of whether or not there is an obligation to disclose the information, to whom does the information belong, and what process should be used to resolve the issue? We present a case that forced us to confront these questions and raised issues of truth telling, autonomy, paternalism, confidentiality, and the nature of the relationship between patients and health care professionals.

  7. 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.…

  8. 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…

  9. 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

  10. Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism.

    PubMed

    Hassaninasab, Azam; Hashimoto, Yoshiteru; Tomita-Yokotani, Kaori; Kobayashi, Michihiko

    2011-04-19

    Polyphenol curcumin, a yellow pigment, derived from the rhizomes of a plant (Curcuma longa Linn) is a natural antioxidant exhibiting a variety of pharmacological activities and therapeutic properties. It has long been used as a traditional medicine and as a preservative and coloring agent in foods. Here, curcumin-converting microorganisms were isolated from human feces, the one exhibiting the highest activity being identified as Escherichia coli. We are thus unique in discovering that E. coli was able to act on curcumin. The curcumin-converting enzyme was purified from E. coli and characterized. The native enzyme had a molecular mass of about 82 kDa and consisted of two identical subunits. The enzyme has a narrow substrate spectrum, preferentially acting on curcumin. The microbial metabolism of curcumin by the purified enzyme was found to comprise a two-step reduction, curcumin being converted NADPH-dependently into an intermediate product, dihydrocurcumin, and then the end product, tetrahydrocurcumin. We named this enzyme "NADPH-dependent curcumin/dihydrocurcumin reductase" (CurA). The gene (curA) encoding this enzyme was also identified. A homology search with the BLAST program revealed that a unique enzyme involved in curcumin metabolism belongs to the medium-chain dehydrogenase/reductase superfamily. PMID:21467222

  11. 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…

  12. 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

  13. Examining the causes of a devastating debris flow

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2014-08-01

    Storm-triggered landslides cause loss of life, property damage, and landscape alterations. For instance, the remnants of Hurricane Camille in 1969 caused 109 deaths in central Virginia, after 600 millimeters of rain fell in mountainous terrain in 6 hours. More recently, on 8 August 2010, a rainstorm-induced landslide devastated the Chinese county of Zhouqu, causing more than 1000 deaths. A new modeling study by Ren examines the multiple factors, natural and human caused, that came together to produce this event. Three things contribute to storm-triggered landslides: geological condition, surface loading and vegetation roots, and extreme precipitation.

  14. Limits to social capital: comparing network assistance in two New Orleans neighborhoods devastated by Hurricane Katrina.

    PubMed

    Elliott, James R; Haney, Timothy J; Sams-Abiodun, Petrice

    2010-01-01

    Sociological research emphasizes that personal networks offer social resources in times of need and that this capacity varies by the social position of those involved. Yet rarely are sociologists able to make direct comparisons of such inequalities. This study overcomes this methodological challenge by examining network activation among residents of two unequal neighborhoods severely devastated by Hurricane Katrina. Results indicate that local network capacities of Lower Ninth Ward residents relative to those of the more affluent Lakeview neighborhood dissipated before, during, and after the disaster to erode the life chances of individual residents and the neighborhood they once constituted. PMID:20939128

  15. Limits to social capital: comparing network assistance in two New Orleans neighborhoods devastated by Hurricane Katrina.

    PubMed

    Elliott, James R; Haney, Timothy J; Sams-Abiodun, Petrice

    2010-01-01

    Sociological research emphasizes that personal networks offer social resources in times of need and that this capacity varies by the social position of those involved. Yet rarely are sociologists able to make direct comparisons of such inequalities. This study overcomes this methodological challenge by examining network activation among residents of two unequal neighborhoods severely devastated by Hurricane Katrina. Results indicate that local network capacities of Lower Ninth Ward residents relative to those of the more affluent Lakeview neighborhood dissipated before, during, and after the disaster to erode the life chances of individual residents and the neighborhood they once constituted.

  16. 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…

  17. The devastating effects a fire burn in a child.

    PubMed

    Istek, Şeref

    2015-06-08

    Burn injuries are a serious global public health concern with significant worldwide mortality and morbidity rates. Burns are among the most devastating of all injuries, with outcomes ranging from physical impairment and disability to emotional and mental consequences. Paediatric burns requiring treatment often incur significant health and opportunity costs, and frequently result in death or long-term disability. A recent systemic review showed that almost 50% of patients hospitalised with severe burns in Europe were younger than 16 years of age, and nearly 60% were male. This report discusses the case of a 2-year-old boy with second and third-degree skin burns over almost 45% of his body, including his head and arms, who presented to the eye clinic at the State Hospital in Hakkari 1 month after a fire burn accident. Both eyes had been burnt and the bilateral anterior chambers had been injured so badly that the patient was left blind.

  18. 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

  19. Active faulting and devastating earthquakes in continental China

    NASA Astrophysics Data System (ADS)

    Zhang, P.

    2003-04-01

    The primary pattern of active tectonics in continental China is characterized by relative movements and interactions of tectonic blocks bounded by major active faults. Earthquakes are results of abrupt releases of accumulated strain energy that excesses the threshold of strength of brittle part of the earth’s crust. Boundaries of tectonic blocks are the locations of most discontinuous deformation and highest gradient of stress accumulation, thus are the most likely places for strain energy accumulation and releases, and in turn, devastating earthquakes. Almost all earthquakes of magnitude larger than 8 and 80~90% of earthquakes of magnitude over 7 occur along boundaries of active tectonic blocks. This fact indicates that differential movements and interactions of active tectonic blocks are the primary mechanism for the occurrences of devastating earthquakes. Northeastern margin of Tibetan Plateau consists of two active fault zones, the Haiyuan and the Xiangshan fault zones. Each of the zones can be further divided into several segments. Historical earthquakes during the past 800 years ruptured all of them except one segment, the so-called Tianzhu seismic gap. We have conducted paleoseismological studies on each of the segments of the fault zones. Preliminary results reveal temporal clustering features of long-term paleoearthquake activity along these two fault zones. The 1920 Haiyuan earthquake of magnitude 8.5, for example, ruptured three segments of the fault zone. We dug 19 trenches along different segments of the surface ruptures. There were 3 events along the eastern segment during the past 14000 years, 7 events along the middle segment during the past 9000 years, and 6 events along the western segment during the past 10000 years. These events clearly depict two temporal clusters. The first cluster occurs from 4600 to 6400 years, and the second occurs from 1000 to 2800 years, approximately. Each cluster lasts about 2000 years. Time period between these two

  20. Ethical issues in the care of the neurologically devastated infant.

    PubMed

    Koogler, Tracy K

    2013-01-01

    The debate surrounding neurologically devastated newborns, whether due to severe prematurity or genetic malformations, has continued for over 40 years. Duff and Campbell (1973) first discussed allowing these children to die in the 1970s. In the 1980s, others fought to make sure these children with disabilities were afforded all the rights of other children. Recently, some commentators have advocated for withdrawal of therapies and even euthanasia in the Netherlands. Who is right? What are the ethical principles that should be followed? What decisions are appropriate for distraught parents to make? This chapter reviews international views, laws, and guidelines surrounding the therapies and limitations of care for these imperiled newborns. An ethical argument is presented for how to determine best interests for these special children utilizing the best interest standard. Parents and physicians need to use their individual expertise and values to work together to determine each individual child's best interests. Physicians may have to carry the burden for making final determinations to alleviate the guilt families may have in deciding to limit therapies.

  1. 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.

  2. 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. PMID:25965304

  3. Devastating renal outcome caused by skin infection with methicillin-resistant Staphylococcus aureus

    PubMed Central

    Liang, Jun-Hua; Fang, Yu-Wei; Yang, An-Hung; Tsai, Ming Hsien

    2016-01-01

    Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen that infects the skin and soft tissue. However, there are few reports of renal complications from MRSA involving immunoglobulin (Ig)A-dominated rapidly progressive glomerulonephritis (GN). Favorable renal outcomes from IgA GN are achieved by administering timely therapy. In the present study, we describe the case of a healthy young woman suffering from a cutaneous MRSA infection that initially presented with gross hematuria. Six months after eradicating the infection, severe impairment of renal function was noted because of intractable nausea and vomiting. Renal pathology revealed advanced IgA nephropathy with fibrocellular crescent formation. An aggressive treatment plan using immunosuppressants was not adopted because of her irreversible renal pathology, and she was therefore administered maintenance hemodialysis. This instructive case stresses the importance of being aware of the signs of IgA nephropathy post-MRSA infection, such as cutaneous lesions that are mostly painless and accompanied by hematuria and mild proteinuria. If the kidney cannot be salvaged, it will undergo irreversible damage with devastating consequences. PMID:27368023

  4. De novo characterization of the Dialeurodes citri transcriptome: mining genes involved in stress resistance and simple sequence repeats (SSRs) discovery.

    PubMed

    Chen, E-H; Wei, D-D; Shen, G-M; Yuan, G-R; Bai, P-P; Wang, J-J

    2014-02-01

    The citrus whitefly, Dialeurodes citri (Ashmead), is one of the three economically important whitefly species that infest citrus plants around the world; however, limited genetic research has been focused on D. citri, partly because of lack of genomic resources. In this study, we performed de novo assembly of a transcriptome using Illumina paired-end sequencing technology (Illumina Inc., San Diego, CA, USA). In total, 36,766 unigenes with a mean length of 497 bp were identified. Of these unigenes, we identified 17,788 matched known proteins in the National Center for Biotechnology Information database, as determined by Blast search, with 5731, 4850 and 14,441 unigenes assigned to clusters of orthologous groups (COG), gene ontology (GO), and SwissProt, respectively. In total, 7507 unigenes were assigned to 308 known pathways. In-depth analysis of the data showed that 117 unigenes were identified as potentially involved in the detoxification of xenobiotics and 67 heat shock protein (Hsp) genes were associated with environmental stress. In addition, these enzymes were searched against the GO and COG database, and the results showed that the three major detoxification enzymes and Hsps were classified into 18 and 3, 6, and 8 annotations, respectively. In addition, 149 simple sequence repeats were detected. The results facilitate the investigation of molecular resistance mechanisms to insecticides and environmental stress, and contribute to molecular marker development. The findings greatly improve our genetic understanding of D. citri, and lay the foundation for future functional genomics studies on this species.

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

    PubMed

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

    2014-08-01

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

  6. 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

  7. 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…

  8. 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...

  9. 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)

  10. 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.

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

    DOE PAGESBeta

    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 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

  12. 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.

  13. 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

  14. The concept of skin bleaching in Africa and its devastating health implications.

    PubMed

    de Souza, Melanie Miyanji

    2008-01-01

    Africa is considered a continent of mystery and intrigue with absurd concepts and beliefs. Cosmetic dermatology is no less intriguing than other issues. While quick judgement may be passed condemning attitudes and misconceptions in this field, we need to analyze factors that contribute to such ideas. Acquiring a lighter skin forms the basis of Skin Care and Cosmetology in dark skinned people. This regrettably has far reaching devastating effects on health and individual finances. This in return has enriched unscrupulous stake holders. Help from the international medical fraternity and the pharmaceutical/cosmetology industry is required to end this evil.

  15. 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.

  16. 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. PMID:26957340

  17. 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.

  18. 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.

  19. 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. 

  20. New Approaches for Controlling Saprolegnia parasitica, the Causal Agent of a Devastating Fish Disease.

    PubMed

    Earle, Gregory; Hintz, William

    2014-12-01

    Pathogenic oomycetes have the ability to infect a wide range of plant and animal hosts and are responsible for a number of economically important diseases. Saprolegniasis, a disease affecting fish eggs and juvenile fish in hatcheries worldwide, is caused by the pathogenic oomycete Saprolegnia parasitica. This disease presents as greyish-white patches of filamentous mycelium on the body or fins of fish and is associated with tissue damage leading to death of the animal. Traditionally, saprolegniasis was controlled using Malachite green; however, this chemical was banned in 2002 due to its carcinogenic and toxicological effects. As a direct result of this ban, there has been a recent resurgence of saprolegniasis in the aquaculture industry, leading to economic losses world-wide. Hence, there is an urgent need to find alternative methods to control this pathogen. We discuss the use of molecular approaches for the study of saprolegniasis, which are anticipated to enable the development of effective fish vaccines and the potential for the development of new methods to control this devastating disease.

  1. 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.

  2. 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

  3. New Approaches for Controlling Saprolegnia parasitica, the Causal Agent of a Devastating Fish Disease

    PubMed Central

    Earle, Gregory; Hintz, William

    2014-01-01

    Pathogenic oomycetes have the ability to infect a wide range of plant and animal hosts and are responsible for a number of economically important diseases. Saprolegniasis, a disease affecting fish eggs and juvenile fish in hatcheries worldwide, is caused by the pathogenic oomycete Saprolegnia parasitica. This disease presents as greyish-white patches of filamentous mycelium on the body or fins of fish and is associated with tissue damage leading to death of the animal. Traditionally, saprolegniasis was controlled using Malachite green; however, this chemical was banned in 2002 due to its carcinogenic and toxicological effects. As a direct result of this ban, there has been a recent resurgence of saprolegniasis in the aquaculture industry, leading to economic losses world-wide. Hence, there is an urgent need to find alternative methods to control this pathogen. We discuss the use of molecular approaches for the study of saprolegniasis, which are anticipated to enable the development of effective fish vaccines and the potential for the development of new methods to control this devastating disease. PMID:27073602

  4. 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.

  5. 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

  6. 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.

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

    PubMed

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

    2016-09-01

    The fission yeast model system Schizosaccharomyces pombe is used to study fundamental biological processes. To continue to fill gaps in the Sz. pombe gene deletion collection, we constructed a set of 90 haploid gene deletion strains covering many previously uncharacterized genes. To begin to understand the function of these genes, we exposed this collection of strains to a battery of stress conditions. Using this information in combination with microscopy, proteomics and mini-chromosome loss assays, we identified genes involved in cell wall integrity, cytokinesis, chromosome segregation and DNA metabolism. This subset of non-essential gene deletions will add to the toolkits available for the study of biological processes in Sz. pombe. Copyright © 2016 John Wiley & Sons, Ltd.

  8. 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)

  9. Seismotectonic Models of the Three Recent Devastating SCR Earthquakes in India

    NASA Astrophysics Data System (ADS)

    Mooney, W. D.; Kayal, J.

    2007-12-01

    During the last decade, three devastating earthquakes, the Killari 1993 (Mb 6.3), Jabalpur 1997 (Mb 6.0) and the Bhuj 2001 (Mw 7.7) occurred in the Stable Continental Region (SCR), Peninsular India. First, the September 30, 1993 Killari earthquake (Mb 6.3) occurred in the Deccan province of central India, in the Latur district of Maharashtra state. The local geology in the area is obscured by the late Cretaceous-Eocene basalt flows, referred to as the Deccan traps. This makes it difficult to recognize the geological surface faults that could be associated with the Killari earthquake. The epicentre was reported at 18.090N and 76.620E, and the focal depth at 7 +/- 1 km was precisely estimated by waveform inversion (Chen and Kao, 1995). The maximum intensity reached to VIII and the earthquake caused a loss of about 10,000 lives and severe damage to property. The May 22, 1997 Jabalpur earthquake (Mb 6.0), epicentre at 23.080N and 80.060E, is a well studied earthquake in the Son-Narmada-Tapti (SONATA) seismic zone. A notable aspects of this earthquake is that it was the first significant event in India to be recorded by 10 broadband seismic stations which were established in 1996 by the India Meteorological Department (IMD). The focal depth was well estimated using the "converted phases" of the broadband seismograms. The focal depth was given in the lower crust at a depth of 35 +/- 1 km, similar to the moderate earthquakes reported from the Amazona ancient rift system in SCR of South America. Maximum MSK intensity of the Jabalpur earthquake reached to VIII in the MSK scale and this earthquake killed about 50 people in the Jabalpur area. Finally, the Bhuj earthquake (MW 7.7) of January 26, 2001 in the Gujarat state, northwestern India, was felt across the whole country, and killed about 20,000 people. The maximum intensity level reached X. The epicenter of the earthquake is reported at 23.400N and 70.280E, and the well estimated focal depth at 25 km. A total of about

  10. 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.

  11. 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

  12. 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. PMID:25685324

  13. Cosmic Discovery

    NASA Astrophysics Data System (ADS)

    Harwit, Martin

    1984-04-01

    In the remarkable opening section of this book, a well-known Cornell astronomer gives precise thumbnail histories of the 43 basic cosmic discoveries - stars, planets, novae, pulsars, comets, gamma-ray bursts, and the like - that form the core of our knowledge of the universe. Many of them, he points out, were made accidentally and outside the mainstream of astronomical research and funding. This observation leads him to speculate on how many more major phenomena there might be and how they might be most effectively sought out in afield now dominated by large instruments and complex investigative modes and observational conditions. The book also examines discovery in terms of its political, financial, and sociological context - the role of new technologies and of industry and the military in revealing new knowledge; and methods of funding, of peer review, and of allotting time on our largest telescopes. It concludes with specific recommendations for organizing astronomy in ways that will best lead to the discovery of the many - at least sixty - phenomena that Harwit estimates are still waiting to be found.

  14. 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.

  15. 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.

  16. Volcanoes generate devastating waves

    SciTech Connect

    Lockridge, P. )

    1988-01-01

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

  17. Devastated 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…

  18. 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.

  19. The awakening from devastation to development. (A case study of the Diviseema Social Service Society (DSSS) in the metamorphosis of the socio-economic conditions in the Diviseema, Andhra Pradesh devastated by the cyclonic tidal wave of November 1977).

    PubMed

    Kumar, P V

    1982-10-01

    This article discusses the objectives and achievements of the Diviseema Social Service Society (DSSS). Diviseema is an Island which was devastated by cyclones and tidal waves on November 19, 1977. An estimated 10,000 people died and about 1,000,000 head of cattle were destroyed. The survivors have recouped, due largely to voluntary organizations and governmental efforts. For long term development program, the Diviseema Social Service Society was formed. It is an autonomous nonprofit organization aimed at the socioeconomic development of the people. Their programs may encompass a wide range of activities in a given sector, such as the agricultural development program. Each sectoral program may have 1 or more subprograms, like crop loans, or agroservices. The bulk of DSSS activities are geared towards programs in agricultural development. The DSSS helps in securing funds and loans for the Island by playing the role of facilitator and liaison agency between the bank and the farmers. The DSSS developmental activities have an underlying communality of vision, which is why they have been successful. Community health services are also an integral component of socio-economic development, with the goal of improving the nutritional standard of villagers to combat malnutrition and anemia. Mother and child health is also a large part, emphasizing food supplements and check-ups. Education for children and adults is another component of the DSSS plan. The program has met with a great deal of success, due largely to the receptive environment in which it operates.

  20. 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. PMID:21843147

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

    PubMed

    Crocitti, John C

    2009-01-01

    This article uses Barra do Piraí as a case study of rural land tenure, production, consumption, and labor in Brazil's Middle Paraíba Valley during the half century following abolition of slavery in 1888. Dairy farming and railroad development distinguished Barra do Piraí from other coffee-producing areas that suffered from ecological devastation. By 1900 the land's loss of fertility precluded further plantation agriculture in Barra do Piraí, leading to the transition from lucrative coffee cultivation to dairy farming based on meager capital inputs. Compared to the earlier coffee culture, dairy farms produced only modest wealth for landlords and required fewer laborers, compelling impoverished tenants to migrate in search of employment. Since Barra do Piraí was an important railroad junction, many rural laborers ended up in the locale after using the railroad as a migratory path. At the same time, the railroad and proto-industries that it stimulated provided alternative employment for rural laborers, thereby partially mitigating the leverage landlords had over the abundant labor force. The availability of industrial and proto-industrial employment created occupational diversity among rural tenants and introduced them to work routines that would become commonplace when the region more fully industrialized after 1940. PMID:19728415

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

    PubMed

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

    2015-08-01

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

  3. Similarities and differences between the massive eel (Anguilla anguilla L.) devastations that occurred in Lake Balaton in 1991 and 1995.

    PubMed

    Bálint, T; Ferenczy, J; Kátai, F; Kiss, I; Kráczer, L; Kufcsák, O; Láng, G; Polyhos, C; Szabó, I; Szegletes, T; Nemcsók, J

    1997-06-01

    In the past few years, two massive eel (Anguilla anguilla L.) devastations occurred in Lake Balaton, Hungary. In 1991, 300 tons of eel perished in the western basin of the lake, while in the summer of 1995 30 tons of eel died in the eastern part of the lake. Investigations carried out to find the causes of these ecocatastrophes included measurements of certain biochemical parameters: the blood sugar level, and the acetylcholinesterase (AChE, EC 3.1.1.7), lactate dehydrogenase (LDH, EC 1.1.2.3), glutamic-oxaloacetic transaminase (GOT, EC 2.6.1.1) and glutamic-pyruvic transaminase (GPT, EC 2.6.1.2) activities in the blood serum of the collected eels. In both 1991 and 1995, deltamethrin (DM), the active ingredient of the insecticide K-OTHRIN 1 ULV used against mosquitoes, was detected in the eels; in 1995 it was demonstrated in several other animal species, i.e., bream (Abramis brama L.), pike perch (Stizostedion lucioperca L.), and the common gull (Larus canus), and in sediment samples from the lake. Additionally, laboratory experiments were carried out to study the effects of DM on eels. In 1991, eels were collected from the western (the site of the devastation) and eastern basins of the lake. The eels from the eastern basin were used as controls. At that time, the AChE activity in the blood serum of the eels from the western basin was significantly inhibited compared to that in animals from the eastern basin (P < 0.05, Student t test). Eels from the western part of the lake had GOT and GPT levels 20 and 100%, respectively, higher than those of eels from the eastern part of the lake. The blood glucose level was much higher in the eels from the affected area of the lake as compared to those from the eastern part. The brain and liver of the eels contained DM residues at 20 micrograms/kg wet tissue (Gönczy, 1992). Gönczy suspected that one of the causes of the massive eel loss in 1991 was the presence of DM in the fish. In 1995, when the eel devastation occurred in

  4. 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.

  5. 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. PMID:26889892

  6. 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…

  7. Solar flare discovery

    NASA Technical Reports Server (NTRS)

    Hudson, Hugh S.

    1987-01-01

    This paper considers the discoveries that have appreciably changed our understanding of the physics of solar flares. A total of 42 discoveries from all disciplines, ranging from Galileo's initial observation of faculae to the recent discovery of strong limb brightening in 10-MeV gamma-radiation, are identified. The rate of discovery increased dramatically over the past four decades as new observational tools became available. The assessment of significance suggests that recent discoveries -though more numerous - are individually less significant; perhaps this is because the minor early discoveries tend to be taken for granted.

  8. 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.

  9. 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

  10. 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

  11. 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. PMID

  12. Partial lateral forcing experiments reveal how multi-scale processes induce devastating rainfall: a new application of regional modeling

    NASA Astrophysics Data System (ADS)

    Yang, Hongwei; Wang, Bin

    2015-09-01

    The 1998 extremely heavy rainfall events over East Asia are investigated through partial lateral forcing (PLF) experiments with the Weather Research and Forecasting model to determine the impacts of the synoptic (SY), intra-seasonal (IS), and inter-annual (IA) forcing across the lateral boundary on the extreme climate anomalies. The large-scale lateral boundary forcing was derived from an ensemble reanalysis dataset and decomposed into climatological, SY, IS, and IA components. The PLF experiments show that the IS forcing not only triggers the monsoon onset and drives two northward propagation events of the subtropical front but also has dominant contributions to the two heaviest rainfall events over the Yangtze River Basin (YRB) and South China, suggesting the critical role of the intra-seasonal variability in the devastating 1998 floods. Previous studies perceived that the northward propagating IS oscillation from the tropics regulates the extreme heavy rainfall of East Asia summer monsoon in 1998. However, we find that the IS forcing from the mid-latitude plays a more important role than the forcing from the tropics in generating the two extreme rainfall events in 1998. During the first extreme event in June, the IS forcing across the western boundary is the major cause of the northward advance of the subtropical front and the heavy rainfall over the YRB and South China, with the IS forcing across the northern boundary providing the second largest contribution. During the second extreme event (July 15-August 5), the IS forcing from the eastern boundary plays a dominant role in driving the southward retreat and northward advance of the subtropical front, causing another heavy rainfall over the YRB and South China. The western and northern IS forcing also has large contributions to the second extreme event. We have estimated the contributions to the seasonal anomalous rainfall by the three types of forcing. The SY forcing tends to have a moderate effect on the YRB

  13. 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.

  14. Controlling false discoveries in genetic studies.

    PubMed

    van den Oord, Edwin J C G

    2008-07-01

    A false discovery occurs when a researcher concludes that a marker is involved in the etiology of the disease whereas in reality it is not. In genetic studies the risk of false discoveries is very high because only few among the many markers that can be tested will have an effect on the disease. In this article, we argue that it may be best to use methods for controlling false discoveries that would introduce the same ratio of false discoveries divided by all rejected tests into the literature regardless of systematic differences between studies. After a brief discussion of traditional "multiple testing" methods, we show that methods that control the false discovery rate (FDR) may be more suitable to achieve this goal. These FDR methods are therefore discussed in more detail. Instead of merely testing for main effects, it may be important to search for gene-environment/covariate interactions, gene-gene interactions or genetic variants affecting disease subtypes. In the second section, we point out the challenges involved in controlling false discoveries in such searches. The final section discusses the role of replication studies for eliminating false discoveries and the complexities associated with the definition of what constitutes a replication and the design of these studies.

  15. 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.

  16. Long-Term Extracorporeal Membrane Oxygenation as Bridging Strategies to Lung Transplantation in Rapidly Devastating Isolated Langerhans Cell Histiocytosis.

    PubMed

    Sacco, Oliviero; Moscatelli, Andrea; Conte, Massimo; Grasso, Chiara; Magnano, Gian Michele; Sementa, Angela Rita; Martelli, Alberto; Rossi, Giovanni A

    2016-05-01

    Isolated pulmonary involvement in pediatric Langerhans cell histiocytosis (LCH) is extremely rare. While the multisystem-LCH course varies from spontaneous remission to rapid deterioration with lethal outcome, single system involvement is generally associated with favorable prognosis. A child with isolated pulmonary LCH had an extremely rapid progression leading to respiratory failure, despite treatment with prednisone and vinblastine. Since lung hyperinflation and cystic degeneration contraindicated conventional mechanical ventilation, extracorporeal membrane oxygenation (ECMO) was chosen for 50 days as a bridge to lung transplantation. The mechanisms involved in disease progression and the usefulness of long-term ECMO are discussed. PMID:26840616

  17. 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.

  18. Antibiotic drug discovery.

    PubMed

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

    2016-09-01

    Due to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a 'New Age of Antibiotic Discovery'. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years. PMID:27470984

  19. Discovery and Classification in Astronomy

    NASA Astrophysics Data System (ADS)

    Dick, Steven J.

    2013-10-01

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

  20. 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.

  1. 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)

  2. 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…

  3. "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…

  4. New strategies in drug discovery.

    PubMed

    Ohlstein, Eliot H; Johnson, Anthony G; Elliott, John D; Romanic, Anne M

    2006-01-01

    Gene identification followed by determination of the expression of genes in a given disease and understanding of the function of the gene products is central to the drug discovery process. The ability to associate a specific gene with a disease can be attributed primarily to the extraordinary progress that has been made in the areas of gene sequencing and information technologies. Selection and validation of novel molecular targets have become of great importance in light of the abundance of new potential therapeutic drug targets that have emerged from human gene sequencing. In response to this revolution within the pharmaceutical industry, the development of high-throughput methods in both biology and chemistry has been necessitated. Further, the successful translation of basic scientific discoveries into clinical experimental medicine and novel therapeutics is an increasing challenge. As such, a new paradigm for drug discovery has emerged. This process involves the integration of clinical, genetic, genomic, and molecular phenotype data partnered with cheminformatics. Central to this process, the data generated are managed, collated, and interpreted with the use of informatics. This review addresses the use of new technologies that have arisen to deal with this new paradigm.

  5. 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.

  6. Viral surveillance and discovery

    PubMed Central

    Lipkin, Walter Ian; Firth, Cadhla

    2014-01-01

    The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health. PMID:23602435

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

    PubMed

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

    2012-09-01

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

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

    PubMed

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

    2012-09-01

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

  9. Drug discovery in academia.

    PubMed

    Shamas-Din, Aisha; Schimmer, Aaron D

    2015-08-01

    Participation of academic centers in aspects of drug discovery and development beyond target identification and clinical trials is rapidly increasing. Yet many academic drug discovery projects continue to stall at the level of chemical probes, and they infrequently progress to drugs suitable for clinical trials. This gap poses a major hurdle for academic groups engaged in drug discovery. A number of approaches have been pursued to overcome this gap, including stopping at the production of high-quality chemical probes, establishing the resources in-house to advance select projects toward clinical trials, partnering with not-for-profit groups to bring the necessary resources and expertise to develop probes into drugs, and drug repurposing, whereby known drugs are advanced into clinical trials for new indications. In this review, we consider the role of academia in anticancer drug discovery and development, as well as the strategies used by academic groups to overcome barriers in this process.

  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. 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.

  12. Toxins and drug discovery.

    PubMed

    Harvey, Alan L

    2014-12-15

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

  13. Implementing a Discovery Layer: A Rookie's Season

    ERIC Educational Resources Information Center

    Brubaker, Noah; Leach-Murray, Susan; Parker, Sherri

    2012-01-01

    The year 2011 was the PALNI (Private Academic Library Network of Indiana) consortium's "rookie season" for the implementation of Primo, the 2010 Discovery Layer 500 race winner. In this article, the authors report on their transition to the cloud within Ex Libris Ltd.'s Primo TotalCare environment: their preparation, the steps involved to move to…

  14. Insecticide discovery: an evaluation and analysis.

    PubMed

    Sparks, Thomas C

    2013-09-01

    There is an on-going need for the discovery and development of new insecticides due to the loss of existing products through the development of resistance, the desire for products with more favorable environmental and toxicological profiles, shifting pest spectrums, and changing agricultural practices. Since 1960, the number of research-based companies in the US and Europe involved in the discovery of new insecticidal chemistries has been declining. In part this is a reflection of the increasing costs of the discovery and development of new pesticides. Likewise, the number of compounds that need to be screened for every product developed has, until recently, been climbing. In the past two decades the agrochemical industry has been able to develop a range of new products that have more favorable mammalian vs. insect selectivity. This review provides an analysis of the time required for the discovery, or more correctly the building process, for a wide range of insecticides developed during the last 60 years. An examination of the data around the time requirements for the discovery of products based on external patents, prior internal products, or entirely new chemistry provides some unexpected observations. In light of the increasing costs of discovery and development, coupled with fewer companies willing or able to make the investment, insecticide resistance management takes on greater importance as a means to preserve existing and new insecticides. PMID:25149229

  15. Insecticide discovery: an evaluation and analysis.

    PubMed

    Sparks, Thomas C

    2013-09-01

    There is an on-going need for the discovery and development of new insecticides due to the loss of existing products through the development of resistance, the desire for products with more favorable environmental and toxicological profiles, shifting pest spectrums, and changing agricultural practices. Since 1960, the number of research-based companies in the US and Europe involved in the discovery of new insecticidal chemistries has been declining. In part this is a reflection of the increasing costs of the discovery and development of new pesticides. Likewise, the number of compounds that need to be screened for every product developed has, until recently, been climbing. In the past two decades the agrochemical industry has been able to develop a range of new products that have more favorable mammalian vs. insect selectivity. This review provides an analysis of the time required for the discovery, or more correctly the building process, for a wide range of insecticides developed during the last 60 years. An examination of the data around the time requirements for the discovery of products based on external patents, prior internal products, or entirely new chemistry provides some unexpected observations. In light of the increasing costs of discovery and development, coupled with fewer companies willing or able to make the investment, insecticide resistance management takes on greater importance as a means to preserve existing and new insecticides.

  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. 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

  18. 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

  19. 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. PMID:27172809

  20. A Decade of Discovery

    SciTech Connect

    2008-01-01

    This book provides a fascinating account of some of the most significant scientific discoveries and technological innovations coming out of the U.S. Department of Energy’s National Laboratories. This remarkable book illustrates how the men and women of the National Laboratories are keeping us on the cutting edge. Though few Americans are familiar with the scope and scale of the work conducted at these National Laboratories, their research is literally changing our lives and bettering our planet. The book describes the scientific discoveries and technological advancements "in recognition of the men and women working in DOE's seventeen national laboratories across the country." Through highly vivid and accessible stories, this book details recent breakthroughs in three critical areas: 1) Energy and Environment, 2) National Security and 3) Life and Physical Science. The book illustrates how this government-funded research has resulted in more energy-efficient buildings; new, cleaner alternative fuels that reduce greenhouse gas emissions; safer, more efficient, nuclear power plants; improved responses to disease outbreaks; more secure and streamlined airport security; more effective treatments for cancer and other diseases; and astonishing discoveries that are altering our understanding of the universe and enabling scientific breakthroughs in fields such as nanotechnology and particle physics. Specifically, it contains 37 stories. A Decade of Discovery is truly a recent history of discovery - and a fascinating look at what the next decade holds.

  1. 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…

  2. The discovery of alkaloids.

    PubMed

    Hosztafi, S

    1997-07-01

    This paper presents the history of the discovery of the first alkaloids. Isolation of alkaloids is connected with the study of the active principles of medicines of plant origin, for example opium and cinchona bark. Sertürner described morphine as a plant alkali and claimed that it was capable of neutralizing free acids yielding salts. The recognition of alkaloids as a new class of compounds was an important step at that time because of the dogmatic denial of the possible existence of plant bases. Isolation of alkaloids is a significant event from the point of view of chemistry, physiology and medicine. The discovery caused essential conceptual changes in chemistry. Priority claims with reference to the discovery of the alkaloids are also reviewed.

  3. The Discovery of Electrography

    NASA Astrophysics Data System (ADS)

    Samuilova, Larissa; Samuilov, Vladimir

    Prof. Jakob Narkiewicz-Jodko (1947-1905) major discoveries are: Electrography - the method of the visualization of corona discharge (corona discharge photography) from the bodies due to the application of high strength and high frequency electric fields, and the first observation of the propagation of the electromagnetic waives for information transfer over the distances. They were made in his laboratory, located at his manor home Nadniemen in Eastern Europe. We describe these experiments and equipment used in the Lab for these discoveries. We also introduce a mathematical algorithm for the analysis of the electrography images.

  4. 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.

  5. Non-instrumented DNA isolation, amplification and microarray-based hybridization for a rapid on-site detection of devastating Phytophthora kernoviae.

    PubMed

    Schwenkbier, Lydia; Pollok, Sibyll; Rudloff, Anne; Sailer, Sebastian; Cialla-May, Dana; Weber, Karina; Popp, Jürgen

    2015-10-01

    A rapid and simple instrument-free detection system was developed for the identification of the plant pathogen Phytophthora kernoviae (P. kernoviae). The on-site operable analysis steps include magnetic particle based DNA isolation, helicase-dependent amplification (HDA) and chip-based DNA hybridization. The isothermal approach enabled the convenient amplification of the yeast GTP-binding protein (Ypt1) target gene in a miniaturized HDA-zeolite-heater (HZH) by an exothermic reaction. The amplicon detection on the chip was performed under room temperature conditions – either by successive hybridization and enzyme binding or by a combined step. A positive signal is displayed by enzymatically generated silver nanoparticle deposits, which serve as robust endpoint signals allowing an immediate visual readout. The hybridization assay enabled the reliable detection of 10 pg μL(-1) target DNA. This is the first report of an entirely electricity-free, field applicable detection approach for devastating Phytophthora species, exemplarily shown for P. kernoviae.

  6. 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…

  7. 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,…

  8. 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)

  9. Birds. Nature Discovery I.

    ERIC Educational Resources Information Center

    Stone, Sally F.

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

  10. 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…

  11. Motivation through Discovery.

    ERIC Educational Resources Information Center

    London, Marilyn

    1984-01-01

    Music motivator projects that enable the elementary teacher to use social science methods (known as ethnomethodology) to observe and learn about students without testing are described. Working in groups and guiding each other, students compose a musical composition and then notate it. Discovery learning is encouraged. (RM)

  12. Scientific Discovery for All

    ERIC Educational Resources Information Center

    Zaikowski, Lori; Lichtman, Paul; Quarless, Duncan

    2007-01-01

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

  13. Ayurvedic drug discovery.

    PubMed

    Balachandran, Premalatha; Govindarajan, Rajgopal

    2007-12-01

    Ayurveda is a major traditional system of Indian medicine that is still being successfully used in many countries. Recapitulation and adaptation of the older science to modern drug discovery processes can bring renewed interest to the pharmaceutical world and offer unique therapeutic solutions for a wide range of human disorders. Eventhough time-tested evidences vouch immense therapeutic benefits for ayurvedic herbs and formulations, several important issues are required to be resolved for successful implementation of ayurvedic principles to present drug discovery methodologies. Additionally, clinical examination in the extent of efficacy, safety and drug interactions of newly developed ayurvedic drugs and formulations are required to be carefully evaluated. Ayurvedic experts suggest a reverse-pharmacology approach focusing on the potential targets for which ayurvedic herbs and herbal products could bring tremendous leads to ayurvedic drug discovery. Although several novel leads and drug molecules have already been discovered from ayurvedic medicinal herbs, further scientific explorations in this arena along with customization of present technologies to ayurvedic drug manufacturing principles would greatly facilitate a standardized ayurvedic drug discovery.

  14. MR1 discovery.

    PubMed

    Hashimoto, Keiichiro

    2016-08-01

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

  15. Discovery and preclinical development of new antibiotics.

    PubMed

    Hughes, Diarmaid; Karlén, Anders

    2014-05-01

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

  16. 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 practices. (DB)

  17. The Discovery Method in Training.

    ERIC Educational Resources Information Center

    Belbin, R. M.

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

  18. Challenges of Antibacterial Discovery

    PubMed Central

    Silver, Lynn L.

    2011-01-01

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

  19. [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.

  20. Discovery concepts for Mars

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  1. The discovery of quarks.

    PubMed

    Riordan, M

    1992-05-29

    Quarks are widely recognized today as being among the elementary particles of which matter is composed. The key evidence for their existence came from a series of inelastic electron-nucleon scattering experiments conducted between 1967 and 1973 at the Stanford Linear Accelerator Center. Other theoretical and experimental advances of the 1970s confirmed this discovery, leading to the present standard model of elementary particle physics.

  2. 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.

  3. 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.

  4. 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

  5. The discovery of stapes.

    PubMed

    Dispenza, F; Cappello, F; Kulamarva, G; De Stefano, A

    2013-10-01

    Giovanni Filippo Ingrassia revisited and redefined some of Galeno's reports, and was recognized as one of the leading Italian Physicians of the 16th century. Ingrassia principally studied the skull, and gave very important contributions to otorhinolaryngology, including the discovery of the stapes. He also isolated the inferior nasal concha from the maxillary bone, described the frontal sinus, the pterygopalatine fossa and several foramina of the skull. Ingrassia firstly attributed a sensorial function to the middle ear bones, which he called fifth particular function. He also added some details to the description of the VIII cranial nerve, which introduces the concept of bone conducting sound. The most important discovery in Ingrassia's study about the hearing organ was the first description of the third bone of the ossicular chain that he called "stapes". Ingrassia should thus be reconsidered under a new light for his important discovery and for his intuitions about the stapes and its role in hearing. It is appropriate for a Sicilian physician to be placed at his rightful place side-by-side with Eustachio and Valsalva in the history of otology.

  6. An Extended Model for E-Discovery Operations

    NASA Astrophysics Data System (ADS)

    Billard, David

    Most models created for electronic discovery (e-discovery) in legal proceedings tend to ignore the technical aspects mainly because they assume that only traditional digital forensic tasks are involved. However, this assumption is incorrect. The time frames for conducting e-discovery procedures are very restricted, and investigations are carried out in real time with strict non-disclosure dispositions and changing demands as the cases unfold. This paper presents an augmented model and architecture for e-discovery designed to cope with the technological complexities in real-world scenarios. It also discusses how e-discovery operations should be handled to ensure cooperation between digital forensic professionals and legal teams while guaranteeing that non-disclosure agreements and information confidentiality are preserved.

  7. 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.

  8. 14 CFR 406.143 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Discovery. 406.143 Section 406.143... Transportation Adjudications § 406.143 Discovery. (a) Initiation of discovery. Any party may initiate discovery... after a complaint has been filed. (b) Methods of discovery. The following methods of discovery...

  9. 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.

  10. Parent Involvement.

    ERIC Educational Resources Information Center

    LaCrosse, Ed

    The paper discusses the rationale and guidelines for parent involvement in HCEEP (Handicapped Children's Early Education Program) projects. Ways of assessing parents' needs are reviewed, as are four types of services to meet the identified needs: parent education, direct participation, parent counseling, and parent provided programs. Materials and…

  11. 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

  12. Discovery by the examiner

    SciTech Connect

    Walterscheid, E.C.

    1981-01-01

    The Manual of Patent Examining Procedure (M.P.E.P.), 4th Edition now has a chapter 2100 on patentability. At present this chapter only contains sections dealing with Patentable Subject Matter - Microorganisms and the Statutory Bars of Public Use and On Sale (35 U.S.C. 102(b), but it is the intent of the Patent and Trademark Office to expand its content as future revisions of the M.P.E.P. are issued. The requirement for information provisions of chapter 2100 - if they are upheld on judicial review - portend a significant change in the relationship of the examiner and the applicant in ex parte prosecution. In view of the fact that the Office positions which appear to herald this change have been adopted without public review or comment, it is imperative that members of the patent bar review them critically and express their concerns to the Office. Simply put, although the M.P.E.P. carefully avoids any use of the term, the Office in chapter 2100 is indicating that an examiner has a right of discovery in ex parte prosecution. Accordingly, the purpose of this article is to discuss the extent to which the Office is attempting to sanction discovery by examiners. In particular, it will explore certain of the ramifications of the requirement for information provisions of chapter 2100. It will begin by outlining the requirements for information in ex parte prosecution which are expressly permitted by the rules of practice. It will then review the authority for discovery requirements in ex parte prosecution and consider the sanction for failure to meet such a requirement. Some consideration will then be given to the extent and effect of a requirement for information presented under the aegis of chapter 2100. The potential for Office discovery in the prosecution of reissue applications will be briefly examined. Finally, the failure of the Office to seek public review or comment in presenting the requirement for information provisions of chapter 2100 will be briefly discussed.

  13. Network discovery with DCM

    PubMed Central

    Friston, Karl J.; Li, Baojuan; Daunizeau, Jean; Stephan, Klaas E.

    2011-01-01

    This paper is about inferring or discovering the functional architecture of distributed systems using Dynamic Causal Modelling (DCM). We describe a scheme that recovers the (dynamic) Bayesian dependency graph (connections in a network) using observed network activity. This network discovery uses Bayesian model selection to identify the sparsity structure (absence of edges or connections) in a graph that best explains observed time-series. The implicit adjacency matrix specifies the form of the network (e.g., cyclic or acyclic) and its graph-theoretical attributes (e.g., degree distribution). The scheme is illustrated using functional magnetic resonance imaging (fMRI) time series to discover functional brain networks. Crucially, it can be applied to experimentally evoked responses (activation studies) or endogenous activity in task-free (resting state) fMRI studies. Unlike conventional approaches to network discovery, DCM permits the analysis of directed and cyclic graphs. Furthermore, it eschews (implausible) Markovian assumptions about the serial independence of random fluctuations. The scheme furnishes a network description of distributed activity in the brain that is optimal in the sense of having the greatest conditional probability, relative to other networks. The networks are characterised in terms of their connectivity or adjacency matrices and conditional distributions over the directed (and reciprocal) effective connectivity between connected nodes or regions. We envisage that this approach will provide a useful complement to current analyses of functional connectivity for both activation and resting-state studies. PMID:21182971

  14. 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.

  15. 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.

  16. Drug discovery today.

    PubMed

    Schwardt, Oliver; Kolb, Hartmuth; Ernst, Beat

    2003-01-01

    In recent years, tools for the development of new drugs have been dramatically improved. These include genomic and proteomic research, numerous biophysical methods, combinatorial chemistry and screening technologies. In addition, early ADMET studies are employed in order to significantly reduce the failure rate in the development of drug candidates. As a consequence, the lead finding, lead optimization and development process has gained marked enhancement in speed and efficiency. In parallel to this development, major pharma companies are increasingly outsourcing many components of drug discovery research to biotech companies. All these measures are designed to address the need for a faster time to market. New screening methodologies have contributed significantly to the efficiency of the drug discovery process. The conventional screening of single compounds or compound libraries has been dramatically accelerated by high throughput screening methods. In addition, in silico screening methods allow the evaluation of virtual compounds. A wide range of new lead finding and lead optimization opportunities result from novel screening methods by NMR, which are the topic of this review article.

  17. 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.

  18. 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.

  19. 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. PMID:23583960

  20. 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 ...

  1. 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.

  2. 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.

  3. 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

  4. Discovery and preclinical development of new antibiotics

    PubMed Central

    Karlén, Anders

    2014-01-01

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

  5. Centennial of Metchnikoff's discovery.

    PubMed

    Heifets, L

    1982-05-01

    Phagocytosis was discovered by Elie Metchnikoff (Ilia Mechnikov) in 1882. Although the phenomenon of endocytosis by the leukocytes (more related to the pinocytosis) had been described 30 years earlier [8], it was Metchnikoff who explained its function, and alerted the scientific community to the importance of phagocytosis in immunity. He devoted most of his life to studying different aspects of phagocytosis and related immunological phenomena. It required 25 years of intense effort to achieve recognition of the phagocytosis theory, the first experimentally based theory in immunology. This struggle culminated in 1908 with the awarding of the Nobel Prize to Metchnikoff and Ehrlich for their two theories of immunity, "cellular" and "humoral," respectively. That was an official recognition of the existence and importance of immunology, but modern immunology began at the moment of Metchnikoff's discovery, which is why 1982 may be considered the 100th year anniversary of immunology. PMID:6750115

  6. Discovery of cosmic rays

    NASA Astrophysics Data System (ADS)

    Carlson, Per

    2013-02-01

    The mysterious invisible radiation that ionized air was studied a century ago by many scientists. Finally, on 7 August 1912, Victor Hess in his seventh balloon flight that year, reached an altitude of about 5000 m. With his electroscopes on board the hydrogen-filled balloon he observed that the ionization instead of decreasing with altitude increased significantly. Hess had discovered cosmic rays, a discovery that gave him the 1936 Nobel Prize in physics. When research resumed after World War I focus was on understanding the nature of the cosmic radiation. Particles or radiation? Positive or negative? Electrons, positrons or protons? Progress came using new instruments like the Geiger-Muller tube and around 1940 it was clear that cosmic rays were mostly protons.

  7. 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.

  8. 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. PMID:22247822

  9. Academic Freedom and Civil Discovery.

    ERIC Educational Resources Information Center

    Hoornstra, Charles D.; Liethen, Michael A.

    1984-01-01

    The ability of a university to do research free from undue interference is discussed in light of two court cases: Buchanan vs. American Motors Corp. and Dow Chemical Co. vs. Allen. Their principal significance lies in sparing nonparty researchers from the discovery process notwithstanding the acknowledged breadth of discovery. (MLW)

  10. 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…

  11. 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…

  12. 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…

  13. 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.

  14. 24 CFR 180.500 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery...

  15. 29 CFR 2700.56 - Discovery; general.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...(c) or 111 of the Act has been filed. 30 U.S.C. 815(c) and 821. (e) Completion of discovery... 29 Labor 9 2010-07-01 2010-07-01 false Discovery; general. 2700.56 Section 2700.56 Labor... Hearings § 2700.56 Discovery; general. (a) Discovery methods. Parties may obtain discovery by one or...

  16. 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.

  17. Novel Directions for Diabetes Mellitus Drug Discovery

    PubMed Central

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

    2012-01-01

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

  18. System for Information Discovery

    SciTech Connect

    Crow, Vern; Nakamura, Grant; Younkin, Chance

    1998-09-25

    SID characterizes natural language based documents so that they may be related and retrieved based on content similarity. This technology processes textual documents, autonoumsly identifies the major topics of the document set, and constructs an interpretable, high dimensional representation of each document. SID also provides the ability to interactively reweight representations based on user need, so users may analyze the dataset from multiple points of view. The particular advantages SID offers are speed, data compression, flexibility in representation, and incremental processing. SPIRE consists of software for visual analysis of text-based information sources. This technology enables users to make discoveries about the content of very large sets of textual documents without requiring the user to read or presort the documents. It employs algorithms for text and word proximity analysis to identify the key themes within the documents. The results of this analysis are projected onto a visual spatial proximity display (Galaxies or Themescape) where document proximity represents the degree of relatedness of theme.

  19. System for Information Discovery

    1998-09-25

    SID characterizes natural language based documents so that they may be related and retrieved based on content similarity. This technology processes textual documents, autonoumsly identifies the major topics of the document set, and constructs an interpretable, high dimensional representation of each document. SID also provides the ability to interactively reweight representations based on user need, so users may analyze the dataset from multiple points of view. The particular advantages SID offers are speed, data compression,more » flexibility in representation, and incremental processing. SPIRE consists of software for visual analysis of text-based information sources. This technology enables users to make discoveries about the content of very large sets of textual documents without requiring the user to read or presort the documents. It employs algorithms for text and word proximity analysis to identify the key themes within the documents. The results of this analysis are projected onto a visual spatial proximity display (Galaxies or Themescape) where document proximity represents the degree of relatedness of theme.« less

  20. 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. PMID:27491648

  1. STS-105 Shuttle Orbiter Discovery

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This is a view of the Space Shuttle Discovery as it approaches the International Space Station (ISS) during the STS-105 mission. Visible in the payload bay of Discovery are the Multipurpose Logistics Module (MPLM) Leonardo at right, which stores various supplies and experiments to be transferred into the ISS; at center, the Integrated Cargo Carrier (ICC) which carries the Early Ammonia Servicer (EAS); and two Materials International Space Station Experiment (MISSE) containers at left. Aboard Discovery were the ISS Expedition Three crew, who were to replace the Expedition Two crew that had been living on the ISS for the past five months.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  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. 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.

  9. Synthetic biology of antimicrobial discovery.

    PubMed

    Zakeri, Bijan; Lu, Timothy K

    2013-07-19

    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.

  10. 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.

  11. 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

  12. Computer-aided drug discovery

    PubMed Central

    Bajorath, Jürgen

    2015-01-01

    Computational approaches are an integral part of interdisciplinary drug discovery research. Understanding the science behind computational tools, their opportunities, and limitations is essential to make a true impact on drug discovery at different levels. If applied in a scientifically meaningful way, computational methods improve the ability to identify and evaluate potential drug molecules, but there remain weaknesses in the methods that preclude naïve applications. Herein, current trends in computer-aided drug discovery are reviewed, and selected computational areas are discussed. Approaches are highlighted that aid in the identification and optimization of new drug candidates. Emphasis is put on the presentation and discussion of computational concepts and methods, rather than case studies or application examples. As such, this contribution aims to provide an overview of the current methodological spectrum of computational drug discovery for a broad audience. PMID:26949519

  13. 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.

  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

    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.

  16. 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.

  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. 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)

  19. 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…

  20. 16 CFR 1025.31 - General provisions governing discovery.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...: (1) In general. Parties may obtain discovery regarding any matter, not privileged, which is within the Commission's statutory authority and is relevant to the subject matter involved in the proceedings... any discoverable matter. It is not ground for objection that the information sought will...

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

    ERIC Educational Resources Information Center

    Gilroy, Pamela J.

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

  2. Drug discovery from plant sources: An integrated approach

    PubMed Central

    Katiyar, Chandrakant; Gupta, Arun; Kanjilal, Satyajyoti; Katiyar, Shefali

    2012-01-01

    New drug discovery is facing serious challenges due to reduction in number of new drug approvals coupled with exorbitant rising cost. Advent of combinatorial chemistry provided new hope of higher success rates of new chemical entities (NCEs); however, even this scientific development has failed to improve the success rate in new drug discovery. This scenario has prompted us to come out with a novel approach of integrated drug discovery, where Ayurvedic wisdom can synergize with drug discovery from plant sources. Initial steps in new drug discovery involve identification of NCEs, which can be either sourced through chemical synthesis or can be isolated from natural products through biological activity guided fractionation. The sources of many of the new drugs and active ingredients of medicines are derived from natural products. The starting point for plant-based new drug discovery should be identification of the right candidate plants by applying Ayurvedic wisdom, traditional documented use, tribal non-documented use, and exhaustive literature search. Frequency analysis of the ingredients of the ancient documented formulations and analysis of their Ayurvedic attributes may provide an in-depth idea of the predominance of particular Ayurvedic characteristics based on which appropriate candidate plants may be selected for bioactivity-based fractionation. The integration of Ayurvedic wisdom with drug discovery also brings the need for a paradigm shift in the extraction process from sequential to parallel extraction. Bioassay-guided fractionation of the identified plant may lead to standardized extract or isolated bioactive druggable compound as the new drug. This integrated approach would lead to saving of cost and time, coupled with enhanced success rate in drug discovery. PMID:23049178

  3. 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

  4. 43 CFR 4.1130 - Discovery methods.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 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...

  5. 49 CFR 1503.633 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or approval of the ALJ,...

  6. 24 CFR 26.18 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... knowledge of any discoverable matter. For good cause, the hearing officer may order discovery of any matter... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 26.18 Section 26.18... PROCEDURES Hearings Before Hearing Officers Discovery § 26.18 Discovery. (a) General. The parties...

  7. 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...; and requests for admission. (b) Discovery may not commence until the matter is pending before...

  8. 31 CFR 16.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... FRAUD CIVIL REMEDIES ACT OF 1986 § 16.21 Discovery. (a) The following types of discovery are authorized... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 16.21 Section 16.21 Money... to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery...

  9. 42 CFR 405.1037 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... original discovery deadline. (5) If the ALJ grants the extension request, it must impose a new discovery... 42 Public Health 2 2010-10-01 2010-10-01 false Discovery. 405.1037 Section 405.1037 Public Health... Appeals Under Original Medicare (Part A and Part B) Alj Hearings § 405.1037 Discovery. (a) General...

  10. 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...

  11. Knowledge discovery for pancreatic cancer using inductive logic programming.

    PubMed

    Qiu, Yushan; Shimada, Kazuaki; Hiraoka, Nobuyoshi; Maeshiro, Kensei; Ching, Wai-Ki; Aoki-Kinoshita, Kiyoko F; Furuta, Koh

    2014-08-01

    Pancreatic cancer is a devastating disease and predicting the status of the patients becomes an important and urgent issue. The authors explore the applicability of inductive logic programming (ILP) method in the disease and show that the accumulated clinical laboratory data can be used to predict disease characteristics, and this will contribute to the selection of therapeutic modalities of pancreatic cancer. The availability of a large amount of clinical laboratory data provides clues to aid in the knowledge discovery of diseases. In predicting the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer, using the ILP model, three rules are developed that are consistent with descriptions in the literature. The rules that are identified are useful to detect the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer and therefore contributed significantly to the decision of therapeutic strategies. In addition, the proposed method is compared with the other typical classification techniques and the results further confirm the superiority and merit of the proposed method. PMID:25075529

  12. Mouse Models of Type 2 Diabetes Mellitus in Drug Discovery.

    PubMed

    Baribault, Helene

    2016-01-01

    Type 2 diabetes is a fast-growing epidemic in industrialized countries, associated with obesity, lack of physical exercise, aging, family history, and ethnic background. Diagnostic criteria are elevated fasting or postprandial blood glucose levels, a consequence of insulin resistance. Early intervention can help patients to revert the progression of the disease together with lifestyle changes or monotherapy. Systemic glucose toxicity can have devastating effects leading to pancreatic beta cell failure, blindness, nephropathy, and neuropathy, progressing to limb ulceration or even amputation. Existing treatments have numerous side effects and demonstrate variability in individual patient responsiveness. However, several emerging areas of discovery research are showing promises with the development of novel classes of antidiabetic drugs.The mouse has proven to be a reliable model for discovering and validating new treatments for type 2 diabetes mellitus. We review here commonly used methods to measure endpoints relevant to glucose metabolism which show good translatability to the diagnostic of type 2 diabetes in humans: baseline fasting glucose and insulin, glucose tolerance test, insulin sensitivity index, and body type composition. Improvements on these clinical values are essential for the progression of a novel potential therapeutic molecule through a preclinical and clinical pipeline.

  13. Knowledge discovery for pancreatic cancer using inductive logic programming.

    PubMed

    Qiu, Yushan; Shimada, Kazuaki; Hiraoka, Nobuyoshi; Maeshiro, Kensei; Ching, Wai-Ki; Aoki-Kinoshita, Kiyoko F; Furuta, Koh

    2014-08-01

    Pancreatic cancer is a devastating disease and predicting the status of the patients becomes an important and urgent issue. The authors explore the applicability of inductive logic programming (ILP) method in the disease and show that the accumulated clinical laboratory data can be used to predict disease characteristics, and this will contribute to the selection of therapeutic modalities of pancreatic cancer. The availability of a large amount of clinical laboratory data provides clues to aid in the knowledge discovery of diseases. In predicting the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer, using the ILP model, three rules are developed that are consistent with descriptions in the literature. The rules that are identified are useful to detect the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer and therefore contributed significantly to the decision of therapeutic strategies. In addition, the proposed method is compared with the other typical classification techniques and the results further confirm the superiority and merit of the proposed method.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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. PMID:26156197

  19. 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.

  20. Fragment-based ligand discovery.

    PubMed

    Fischer, Marcus; Hubbard, Roderick E

    2009-02-01

    From home building and decor to mass production, modular design is a standard feature of the modern age. The concept also promises to define drug discovery efforts in the near future, as a wide range of methodologies, from NMR to X-ray crystallography, are being adapted to high-throughput platforms. In particular, "fragment-based ligand discovery" describes the laboratory-driven evolution of drugs from libraries of chemical building blocks. "Evolution" is an apt word for the process, as a wide array of methods are used to define how compound fragments can be best fit into the binding sites of medically relevant target biomolecules. A number of compounds that evolved from fragments have entered the clinic, and the approach is increasingly accepted as an additional route to identifying new hit compounds in pharmaceutical discovery and inhibitor design. PMID:19299661

  1. Evolutionary inspirations for drug discovery.

    PubMed

    Zhang, Hong-Yu; Chen, Ling-Ling; Li, Xue-Juan; Zhang, Jian

    2010-10-01

    Conceptual innovations are needed to address the challenge of 'more investments, fewer drugs' in the pharmaceutical industry. Since the publication of The Origin of Species by Charles Darwin 150 years ago, evolution has been a central concept in biology. In this article, we show that evolutionary concepts are also helpful to streamline the drug-discovery pipeline through facilitating the discovery of targets and drug candidates. Furthermore, the antioxidant paradox can be addressed by an evolutionary methodology. Through examining the evolved biological roles of natural polyphenols (which dominate current antioxidant drug discovery), we reveal that polyphenols (particularly flavonoids) are not evolved for scavenging free radicals. This finding provides new clues to understanding why the strong in vitro antioxidant activities of polyphenols cannot be translated into in vivo effects. Polyphenols have evolved a superior ability to bind various proteins, so we also argue that they are good starting points for multi-target drugs. PMID:20724009

  2. Supporting knowledge discovery in medicine.

    PubMed

    Girardi, Dominic; Arthofer, Klaus

    2014-01-01

    Our ontology-based benchmarking infrastructure for hospitals, we presented on the eHealth 2012, has meanwhile proven useful. Besides, we gathered manifold experience in supporting knowledge discovery in medicine. This also led to further functions and plans with our software. We could confirm and extent our experience by a literature review on the knowledge discovery process in medicine, visual analytics and data mining and drafted an according approach for extending our software. We validated our approach by exemplarily implementing a parallel-coordinate data visualization into our software and plan to integrate further algorithms for visual analytics and machine learning to support knowledge discovery in medicine in diverse ways. This is very promising but can also fail due to technical or organizational details.

  3. Evolutionary inspirations for drug discovery.

    PubMed

    Zhang, Hong-Yu; Chen, Ling-Ling; Li, Xue-Juan; Zhang, Jian

    2010-10-01

    Conceptual innovations are needed to address the challenge of 'more investments, fewer drugs' in the pharmaceutical industry. Since the publication of The Origin of Species by Charles Darwin 150 years ago, evolution has been a central concept in biology. In this article, we show that evolutionary concepts are also helpful to streamline the drug-discovery pipeline through facilitating the discovery of targets and drug candidates. Furthermore, the antioxidant paradox can be addressed by an evolutionary methodology. Through examining the evolved biological roles of natural polyphenols (which dominate current antioxidant drug discovery), we reveal that polyphenols (particularly flavonoids) are not evolved for scavenging free radicals. This finding provides new clues to understanding why the strong in vitro antioxidant activities of polyphenols cannot be translated into in vivo effects. Polyphenols have evolved a superior ability to bind various proteins, so we also argue that they are good starting points for multi-target drugs.

  4. Cellular biosensors for drug discovery.

    PubMed

    Durick, K; Negulescu, P

    2001-09-01

    Recent advances in cell biology, fluorescent probe chemistry, miniaturization and automation have allowed the use of mammalian cells in a variety of medical and industrial applications. Here we describe the generation of cell-based biosensors, engineered to optically report specific biological activity. Cellular biosensors are comprised of living cells and can be used in various applications, including screening chemical libraries for drug discovery and environmental sensing. Panels of biosensors may also be useful for elucidating the function of novel genes. Here we describe two examples of the construction and use of engineered cell lines as biosensors for drug discovery.

  5. Resource Discovery on the Internet

    NASA Astrophysics Data System (ADS)

    Adorf, H.-M.

    The prime sources for astronomical information resources on the Internet are the AstroWeb and the Star ∗s databases. For topics not covered by these databases, the Internet hosts a bewildering variety of resource discovery services including AliWeb, Harvest, InfoSeek, Lycos, WebCrawler, and the WWW Worm. These and other discovery tools are reviewed. They can be used to locate e.g. on-line library services, books and CD-ROMs, software, and people's e-mail addresses.

  6. Advancements in Aptamer Discovery Technologies.

    PubMed

    Gotrik, Michael R; Feagin, Trevor A; Csordas, Andrew T; Nakamoto, Margaret A; Soh, H Tom

    2016-09-20

    Affinity reagents that specifically bind to their target molecules are invaluable tools in nearly every field of modern biomedicine. Nucleic acid-based aptamers offer many advantages in this domain, because they are chemically synthesized, stable, and economical. Despite these compelling features, aptamers are currently not widely used in comparison to antibodies. This is primarily because conventional aptamer-discovery techniques such as SELEX are time-consuming and labor-intensive and often fail to produce aptamers with comparable binding performance to antibodies. This Account describes a body of work from our laboratory in developing advanced methods for consistently producing high-performance aptamers with higher efficiency, fewer resources, and, most importantly, a greater probability of success. We describe our efforts in systematically transforming each major step of the aptamer discovery process: selection, analysis, and characterization. To improve selection, we have developed microfluidic devices (M-SELEX) that enable discovery of high-affinity aptamers after a minimal number of selection rounds by precisely controlling the target concentration and washing stringency. In terms of improving aptamer pool analysis, our group was the first to use high-throughput sequencing (HTS) for the discovery of new aptamers. We showed that tracking the enrichment trajectory of individual aptamer sequences enables the identification of high-performing aptamers without requiring full convergence of the selected aptamer pool. HTS is now widely used for aptamer discovery, and open-source software has become available to facilitate analysis. To improve binding characterization, we used HTS data to design custom aptamer arrays to measure the affinity and specificity of up to ∼10(4) DNA aptamers in parallel as a means to rapidly discover high-quality aptamers. Most recently, our efforts have culminated in the invention of the "particle display" (PD) screening system, which

  7. Advancements in Aptamer Discovery Technologies.

    PubMed

    Gotrik, Michael R; Feagin, Trevor A; Csordas, Andrew T; Nakamoto, Margaret A; Soh, H Tom

    2016-09-20

    Affinity reagents that specifically bind to their target molecules are invaluable tools in nearly every field of modern biomedicine. Nucleic acid-based aptamers offer many advantages in this domain, because they are chemically synthesized, stable, and economical. Despite these compelling features, aptamers are currently not widely used in comparison to antibodies. This is primarily because conventional aptamer-discovery techniques such as SELEX are time-consuming and labor-intensive and often fail to produce aptamers with comparable binding performance to antibodies. This Account describes a body of work from our laboratory in developing advanced methods for consistently producing high-performance aptamers with higher efficiency, fewer resources, and, most importantly, a greater probability of success. We describe our efforts in systematically transforming each major step of the aptamer discovery process: selection, analysis, and characterization. To improve selection, we have developed microfluidic devices (M-SELEX) that enable discovery of high-affinity aptamers after a minimal number of selection rounds by precisely controlling the target concentration and washing stringency. In terms of improving aptamer pool analysis, our group was the first to use high-throughput sequencing (HTS) for the discovery of new aptamers. We showed that tracking the enrichment trajectory of individual aptamer sequences enables the identification of high-performing aptamers without requiring full convergence of the selected aptamer pool. HTS is now widely used for aptamer discovery, and open-source software has become available to facilitate analysis. To improve binding characterization, we used HTS data to design custom aptamer arrays to measure the affinity and specificity of up to ∼10(4) DNA aptamers in parallel as a means to rapidly discover high-quality aptamers. Most recently, our efforts have culminated in the invention of the "particle display" (PD) screening system, which

  8. 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

  9. 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?

  10. 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.

  11. 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.

  12. [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.

  13. 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.

  14. Supporting Discovery in Virtual Libraries.

    ERIC Educational Resources Information Center

    Desai, Bipin C.

    1997-01-01

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

  15. 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…

  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. PMID:26330257

  17. 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…

  18. 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…

  19. 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…

  20. A Discovery Approach to Movement.

    ERIC Educational Resources Information Center

    O'Hagin, Isabel B.

    1998-01-01

    Investigates the effects of the discovery approach to movement-based instruction on children's level of musicality. Finds that the students with the highest musicality were girls, demonstrated reflective movements and a personal sense of style while moving, and made sense of the music by organizing, categorizing, and developing movement ideas.…

  1. 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…

  2. 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…

  3. 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.

  4. 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.

  5. 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.

  6. Systemic involvement in mycosis fungoides.

    PubMed

    Burg, Günter

    2015-01-01

    Mycosis fungoides (MF) represents almost 50% of all primary cutaneous lymphomas and more than 70% of cutaneous T-cell lymphomas (CTCL). Arising from preferentially skin-homing lymphocytes with genetic instability, MF evolves through stages (IA-IVB), producing inconspicuous inflammatory features in the beginning and finally resulting in a proliferation of cytomorphologic, phenotypic, and genotypic abnormal tumor cells. Over the past 200 years, there has been much confusion in the classification of lymphomas due to semantic disagreements (MF, CTCL, parapsoriasis, lymphosarcoma, reticulum cell sarcoma, and many other terms), lack of diagnostic standard criteria, and new molecular diagnostic methods. Studies on extracutaneous involvement in early stages (IA-IIA) are almost completely lacking. In advanced stages of MF (IIB-IVB), discovery of extracutaneous involvement is dependent on the methods used (physical examination, technology, molecular diagnostics, autopsy, and laparoscopy) and reveals a wide range of results. Due to the inflammation-simulating features in the beginning of the disease, early diagnosis is very difficult to assess. Extracutaneous involvement has previously been documented in more than 70% of autopsies. More recent studies give much lower figures. Like all lymphomas, MF is a systemic disease from the very beginning, with distinct homing preferences in tumor cells. Organs most commonly involved during the lengthy course of the disease are, in descending frequency, lymph node/peripheral blood, liver, spleen, lung, bone marrow, GI tract, pancreas, and kidney. PMID:26321404

  7. Shuttle Discovery Landing at Edwards

    NASA Technical Reports Server (NTRS)

    1989-01-01

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

  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. Putting Down the Discovery Learning Hypothesis

    ERIC Educational Resources Information Center

    Chambers, David W.

    1971-01-01

    The author analyzes some of the conceptual problems which have prevented a direct test of the discovery learning hypothesis, provides an operational definition of discovery learning, and proposes an improved experimental paradigm. Appended are 38 references. (AA)

  10. 22 CFR 224.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... document or the truth of any relevant fact; (3) Written interrogatories; and (4) Depositions. (b) For...

  11. 38 CFR 42.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... IMPLEMENTING THE PROGRAM FRAUD CIVIL REMEDIES ACT § 42.21 Discovery. (a) The following types of discovery are... of the authenticity of any relevant document or the truth of any relevant fact; (3)...

  12. 40 CFR 27.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for... truth of any relevant fact; (3) Written interrogatories; and (4) Depositions. (b) For the purpose...

  13. 43 CFR 35.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AND STATEMENTS § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests... authenticity of any relevant document or of the truth of any relevant fact; (3) Written interrogatories; and...

  14. 5 CFR 185.122 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... § 185.122 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... document or of the truth of any relevant fact; (3) Written interrogatories; and (4) Depositions. (b)...

  15. 15 CFR 25.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for... truth of any relevant fact; (3) Written interrogatories; and (4) Depositions. (b) For the purpose...

  16. 24 CFR 26.42 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... subject to a protective order under § 26.44. (c) Authorized discovery. The following types of discovery... or of the truth of any relevant matters of fact. Copies of documents shall be delivered with...

  17. 22 CFR 521.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests for admissions of the authenticity of any relevant document or the...

  18. 14 CFR 1264.120 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... PENALTIES ACT OF 1986 § 1264.120 Discovery. (a) The following types of discovery are authorized: (1... authenticity of any relevant document or of the truth of any relevant fact; (3) Written interrogatories; and...

  19. 49 CFR 511.31 - General provisions governing discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ADJUDICATIVE PROCEDURES Discovery; Compulsory Process § 511.31 General provisions governing discovery. (a) Applicability. The discovery...

  20. 37 CFR 2.120 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  1. 29 CFR 18.13 - Discovery methods.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false 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...

  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 1955.32 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Discovery. 1955.32 Section 1955.32 Labor Regulations...) PROCEDURES FOR WITHDRAWAL OF APPROVAL OF STATE PLANS Preliminary Conference and Discovery § 1955.32 Discovery... the remainder. An answering party may not give lack of information or knowledge as the reason...

  4. 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...

  5. 6 CFR 13.21 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 6 Domestic Security 1 2011-01-01 2011-01-01 false Discovery. 13.21 Section 13.21 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) In general. (1) The following types of discovery are authorized: (i) Requests for production...

  6. 6 CFR 13.21 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 6 Domestic Security 1 2012-01-01 2012-01-01 false Discovery. 13.21 Section 13.21 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) In general. (1) The following types of discovery are authorized: (i) Requests for production...

  7. 43 CFR 4.826 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the Interior-Effectuation of Title VI of the Civil Rights Act of 1964 Procedures § 4.826 Discovery. (a) Methods. Parties may obtain discovery as provided in these rules by depositions, written interrogatories... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery. 4.826 Section 4.826...

  8. 10 CFR 13.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 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... of the authenticity of any relevant document or of the truth of any relevant fact; (3)...

  9. 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...

  10. Discovery in Science and in Teaching Science

    ERIC Educational Resources Information Center

    Kipnis, Nahum

    2007-01-01

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

  11. Small-molecule microarrays as tools in ligand discovery

    PubMed Central

    Vegas, Arturo J.; Fuller, Jason H.; Koehler, Angela N.

    2009-01-01

    Small molecules that bind and modulate specific protein targets are increasingly used as tools to decipher protein function in a cellular context. Identifying specific small-molecule probes for each protein in the proteome will require miniaturized assays that permit screening large collections of compounds against large numbers of proteins in a highly parallel fashion. Simple and general binding assays involving small-molecule microarrays can be used to identify probes for nearly any protein in the proteome. The assay may be used to identify ligands for proteins in the absence of knowledge about structure or function. In this tutorial review, we introduce small-molecule microarrays (SMMs) as tools for ligand discovery; discuss methods for manufacturing SMMs, including both non-covalent and covalent attachment strategies; and provide examples of ligand discovery involving SMMs. PMID:18568164

  12. 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

  13. Enteric Neurobiology: Discoveries and Directions.

    PubMed

    Wood, Jackie D

    2016-01-01

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

  14. Materials discovery via CALYPSO methodology

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  15. 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

  16. The clinical discovery of imipramine.

    PubMed

    Brown, Walter A; Rosdolsky, Maria

    2015-05-01

    The major classes of psychotropic drugs were introduced in an extraordinary decade of discovery between the late 1940s and late 1950s. In the present climate of pessimism about the absence of new drug development, it may be instructive to look back at the research methods used during that era. The study that identified the first antidepressant is a case in point. It was conducted by Roland Kuhn, a Swiss psychiatrist working in a remote psychiatric hospital. Kuhn, like the other pioneering researchers of his day, was given access to new drug entities, and the method he used to discover their clinical effects was open-minded, exploratory, comprehensive, clinical observation. The paper that reported the results of his study has not been available in English, but because of its historical significance and because Kuhn's achievement stands in such contrast to the present impasse in drug development, the authors thought that it might be informative to read about his discovery in his own words. Accordingly, one of the authors (M.R.) translated the paper into English, and they now present excerpts of that translation with the intent of encouraging reevaluation of contemporary approaches to drug discovery. By today's clinical research standards, Kuhn's method of unfettered, exploratory, clinical observation was substandard, haphazard, even messy. Yet it produced a major breakthrough-the discovery that a drug can alleviate depression-that has had a lasting impact on the treatment of depression and on the development of antidepressant drugs. Kuhn's experience might usefully inform our strategies of drug development. PMID:25930134

  17. 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. PMID:27534704

  18. Discovery External Tank Connection Check

    NASA Technical Reports Server (NTRS)

    1999-01-01

    In the Vehicle Assembly Building, Ken Strite, NASA Quality Control, inspects the connection between Space Shuttle Discovery and the external tank that will be used to launch mission STS-103 in early December. This 10 day mission is designed to replace aging parts on the nine year old Hubble Space Telescope and to upgrade some of its functioning systems. During the flight, the astronaut crew will replace all six of the observatory's gyroscopes, a fine guidance sensor, its main computer, and other equipment.

  19. Five Years of GWAS Discovery

    PubMed Central

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

    2012-01-01

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

  20. The Discovery of Sgr A*

    NASA Astrophysics Data System (ADS)

    Balick, Bruce

    2005-01-01

    The discovery of the point-like radio source at the center of the Galaxy, colloquially termed Sgr A*, was made in February 1974 by Balick and Brown using the then-new 35km baseline interferometer between Green Bank and a remote site near Huntersville, WV. The highly unusual properties of the radio source are now well studied; however, the story behind the discovery is equally interesting. Although the signal from the source was strong (˜0.5 Jy) and the peak measured surface brightness quite high (˜107K), the interpretation of the signal as a single point source was initially obscured by the odd geometry of the synthesized aperture. In addition, two groups unknowingly competed to make the detection observations, both based on very different scientific rationales. The other group, comprising Downes and Goss, correctly anticipated the astronomical significance of the discovery but could not make their way from Europe to Green Bank when their observations were scheduled in the fall of 1973.

  1. 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.

  2. 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.

  3. 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. PMID:23798048

  4. 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

  5. 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

  6. Optimizing Viral Discovery in Bats.

    PubMed

    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

  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. Current applications of liquid chromatography/mass spectrometry in pharmaceutical discovery after a decade of innovation.

    PubMed

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

    2008-01-01

    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.

  10. 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.

  11. 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. PMID:25829283

  12. The role of serendipity in drug discovery

    PubMed Central

    Ban, Thomas A.

    2006-01-01

    Serendipity is one of the many factors that may contribute to drug discovery. It has played a role in the discovery of prototype psychotropic drugs that led to modern pharmacological treatment in psychiatry. It has also played a role in the discovery of several drugs that have had an impact on the development of psychiatry, “Serendipity” in drug discovery implies the finding of one thing while looking for something else. This was the case in six of the twelve serendipitous discoveries reviewed in this paper, ie, aniline purple, penicillin, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine, in the case of three drugs, ie, potassium bromide, chloral hydrate, and lithium, the discovery was serendipitous because an utterly false rationale led to correct empirical results; and in case of two others, ie, iproniazid and sildenafil, because valuable indications were found for these drugs which were not initially those sought. The discovery of one of the twelve drugs, chlordiazepoxide, was sheer luck. PMID:17117615

  13. [Ocular involvement in familial amyloid polyneuropathy].

    PubMed

    Rousseau, A; Kaswin, G; Adams, D; Cauquil, C; Théaudin, M; Mincheva, Z; M'garrech, M; Labetoulle, M; Barreau, E

    2013-11-01

    Familial amyloid polyneuropathy (FAP) or transthyretin (TTR) amyloid polyneuropathy is a progressive sensorimotor and autonomic neuropathy of adult onset, which is transmitted as an autosomal dominant trait. In addition to neurologic symptoms, FAP may be associated with weight loss, cardiac and renal failure and ocular complications. FAP is a devastating disease, causing death within 10years after the first symptoms. The TTR Val30Met mutation is the most common of more than 100 amyloidogenic mutations identified worldwide. Liver transplantation (LT) is currently the only treatment for preventing synthesis of the amyloidogenic variants of TTR. LT can halt progression of the neuropathy in up to 70% of cases and doubles the overall median survival of young Val30Met patients. Oral administration of tafamidis, which prevents deposition of mutated TTR, is now available to delay neurologic complications in early stages of the disease. Ocular manifestations of FAP are frequent and mainly include keratoconjunctivitis sicca, secondary glaucoma, vitreous deposits and pupillary abnormalities. Retinal and choroidal vascular abnormalities are more rare. Since ocular TTR is synthesized, at least in part, in the retinal pigment epithelium, LT does not influence the course of ocular involvement. The effects of tafamidis on the latter are still unknown. Because LT and symptomatic treatments greatly improve life expectancy of patients with FAP, ocular involvement is becoming a more frequent challenge to address. This review summarizes the pathophysiology, clinical findings and possible treatments of ocular manifestations of FAP. PMID:24144522

  14. Diabetes Mellitus: Channeling Care through Cellular Discovery

    PubMed Central

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

    2010-01-01

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

  15. Obesity and diabetes gene discovery approaches.

    PubMed

    Walder, K; Segal, D; Jowett, J; Blangero, J; Collier, G R

    2003-01-01

    New treatments are currently required for the common metabolic diseases obesity and type 2 diabetes. The identification of physiological and biochemical factors that underlie the metabolic disturbances observed in obesity and type 2 diabetes is a key step in developing better therapeutic outcomes. The discovery of new genes and pathways involved in the pathogenesis of these diseases is critical to this process, however identification of genes that contribute to the risk of developing these diseases represents a significant challenge as obesity and type 2 diabetes are complex diseases with many genetic and environmental causes. A number of diverse approaches have been used to discover and validate potential new targets for obesity and diabetes. To date, DNA-based approaches using candidate gene and genome-wide linkage analysis have had limited success in identifying genomic regions or genes involved in the development of these diseases. Recent advances in the ability to evaluate linkage analysis data from large family pedigrees using variance components based linkage analysis show great promise in robustly identifying genomic regions associated with the development of obesity and diabetes. RNA-based technologies such as cDNA microarrays have identified many genes differentially expressed in tissues of healthy and diseased subjects. Using a combined approach, we are endeavouring to focus attention on differentially expressed genes located in chromosomal regions previously linked with obesity and/or diabetes. Using this strategy, we have identified Beacon as a potential new target for obesity and diabetes.

  16. 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

  17. Evaluating the inverse reasoning account of object discovery.

    PubMed

    Carroll, Christopher D; Kemp, Charles

    2015-06-01

    People routinely make inferences about unobserved objects. A hotel guest with welts on his arms, for example, will often worry about bed bugs. The discovery of unobserved objects almost always involves a backward inference from some observed effects (e.g., welts) to unobserved causes (e.g., bed bugs). The inverse reasoning account, which is typically formalized as Bayesian inference, posits that the strength of a backward inference is closely connected to the strength of the corresponding forward inference from the unobserved causes to the observed effects. We evaluated the inverse reasoning account of object discovery in three experiments where participants were asked to discover the unobserved "attractors" and "repellers" that controlled a "particle" moving within an arena. Experiments 1 and 2 showed that participants often failed to provide the best explanations for various particle motions, even when the best explanations were simple and when participants enthusiastically endorsed these explanations when presented with them. This failure demonstrates that object discovery is critically dependent on the processes that support hypothesis generation-processes that the inverse reasoning account does not explain. Experiment 3 demonstrated that people sometimes generate explanations that are invalid even according to their own forward inferences, suggesting that the psychological processes that support forward and backward inference are less intertwined than the inverse reasoning account suggests. The experimental findings support an alternative account of object discovery in which people rely on heuristics to generate possible explanations.

  18. Evaluating the inverse reasoning account of object discovery.

    PubMed

    Carroll, Christopher D; Kemp, Charles

    2015-06-01

    People routinely make inferences about unobserved objects. A hotel guest with welts on his arms, for example, will often worry about bed bugs. The discovery of unobserved objects almost always involves a backward inference from some observed effects (e.g., welts) to unobserved causes (e.g., bed bugs). The inverse reasoning account, which is typically formalized as Bayesian inference, posits that the strength of a backward inference is closely connected to the strength of the corresponding forward inference from the unobserved causes to the observed effects. We evaluated the inverse reasoning account of object discovery in three experiments where participants were asked to discover the unobserved "attractors" and "repellers" that controlled a "particle" moving within an arena. Experiments 1 and 2 showed that participants often failed to provide the best explanations for various particle motions, even when the best explanations were simple and when participants enthusiastically endorsed these explanations when presented with them. This failure demonstrates that object discovery is critically dependent on the processes that support hypothesis generation-processes that the inverse reasoning account does not explain. Experiment 3 demonstrated that people sometimes generate explanations that are invalid even according to their own forward inferences, suggesting that the psychological processes that support forward and backward inference are less intertwined than the inverse reasoning account suggests. The experimental findings support an alternative account of object discovery in which people rely on heuristics to generate possible explanations. PMID:25824861

  19. 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...) Admissions (§ 12.33). (b) Scope of discovery. The scope of discovery is as follows: (1) Relevancy. Except...

  20. Discovery of a Makemakean Moon

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

    We describe the discovery of a satellite in orbit about the dwarf planet (136472) Makemake. This satellite, provisionally designated S/2015 (136472) 1, was detected in imaging data collected with the Hubble Space Telescope’s Wide Field Camera 3 on UTC 2015 April 27 at 7.80 ± 0.04 mag fainter than Makemake and at a separation of 0.″57. It likely evaded detection in previous satellite searches due to a nearly edge-on orbital configuration, placing it deep within the glare of Makemake during a substantial fraction of its orbital period. This configuration would place Makemake and its satellite near a mutual event season. Insufficient orbital motion was detected to make a detailed characterization of its orbital properties, prohibiting a measurement of the system mass with the discovery data alone. Preliminary analysis indicates that if the orbit is circular, its orbital period must be longer than 12.4 days and must have a semimajor axis ≳21,000 km. We find that the properties of Makemake’s moon suggest that the majority of the dark material detected in the system by thermal observations may not reside on the surface of Makemake, but may instead be attributable to S/2015 (136472) 1 having a uniform dark surface. This “dark moon hypothesis” can be directly tested with future James Webb Space Telescope observations. We discuss the implications of this discovery for the spin state, figure, and thermal properties of Makemake and the apparent ubiquity of trans-Neptunian dwarf planet satellites.

  1. Metagenomic biomarker discovery and explanation

    PubMed Central

    2011-01-01

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

  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. Metadata-Centric Discovery Service

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

  4. Medical knowledge discovery and management.

    PubMed

    Prior, Fred

    2009-05-01

    Although the volume of medical information is growing rapidly, the ability to rapidly convert this data into "actionable insights" and new medical knowledge is lagging far behind. The first step in the knowledge discovery process is data management and integration, which logically can be accomplished through the application of data warehouse technologies. A key insight that arises from efforts in biosurveillance and the global scope of military medicine is that information must be integrated over both time (longitudinal health records) and space (spatial localization of health-related events). Once data are compiled and integrated it is essential to encode the semantics and relationships among data elements through the use of ontologies and semantic web technologies to convert data into knowledge. Medical images form a special class of health-related information. Traditionally knowledge has been extracted from images by human observation and encoded via controlled terminologies. This approach is rapidly being replaced by quantitative analyses that more reliably support knowledge extraction. The goals of knowledge discovery are the improvement of both the timeliness and accuracy of medical decision making and the identification of new procedures and therapies.

  5. Knowledge discovery by accuracy maximization.

    PubMed

    Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

    2014-04-01

    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.

  6. The story of insulin discovery.

    PubMed

    Karamitsos, Dimitrios T

    2011-08-01

    Many researchers had tried to isolate insulin from animal pancreas, but Frederick Banting, a young surgeon, and Charles Best, a medical student, were the ones that succeeded. They both worked hard in very difficult conditions in the late 1921 and early 1922 until final success. They encountered problems with the impurities of their extract that was causing inflammations, but J. Collip, their late biochemist collaborator, worked many hours and was soon able to prepare cleaner insulin, free from impurities. This extract was administered successfully to L. Thomson, a ketotic young diabetic patient, on 23 January 1922. Following this, Eli Lilly & Co of USA started the commercial production of insulin, soon followed by the Danish factories Nordisc and NOVO as well as the British Wellcome. Nicolae Paulescu who was professor of Physiology in Bucharest, was also quite close to the discovery of insulin but the researchers in Toronto were faster and more efficient. Banting and Macleod won the Nobel price, which Banting shared with Best and Macleod with J. Collip. The contribution of Paulescu in insulin discovery was recognized after his death. PMID:21864746

  7. 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.

  8. Discoveries, financial strength lift Colombia

    SciTech Connect

    Koen, A.D.

    1996-07-15

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

  9. 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

  10. 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.

  11. Virtual screening for lead discovery.

    PubMed

    Tang, Yat T; Marshall, Garland R

    2011-01-01

    The identification of small drug-like compounds that selectively inhibit the function of biological targets has historically been a major focus in the pharmaceutical industry, and in recent years, has generated much interest in academia as well. Drug-like compounds are valuable as chemical genetics tools to probe biological pathways in a reversible, dose- and time-dependent manner for drug target identification. In addition, small molecule compounds can be used to characterize the shape and charge preferences of macromolecular binding sites, for both structure-based and ligand-based drug design. High-throughput screening is the most common experimental method used to identify lead compounds. Because of the cost, time, and resources required for performing high-throughput screening for compound libraries, the use of alternative strategies is necessary for facilitating lead discovery. Virtual screening has been successful in prioritizing large chemical libraries to identify experimentally active compounds, serving as a practical and effective alternative to high-throughput screening. Methodologies used in virtual screening such as molecular docking and scoring have advanced to the point where they can rapidly and accurately identify lead compounds in addition to predicting native binding conformations. This chapter provides instructions on how to perform a virtual screen using freely available tools for structure-based lead discovery. PMID:21318897

  12. Vestibular pathways involved in cognition

    PubMed Central

    Hitier, Martin; Besnard, Stephane; Smith, Paul F.

    2014-01-01

    Recent discoveries have emphasized the role of the vestibular system in cognitive processes such as memory, spatial navigation and bodily self-consciousness. A precise understanding of the vestibular pathways involved is essential to understand the consequences of vestibular diseases for cognition, as well as develop therapeutic strategies to facilitate recovery. The knowledge of the “vestibular cortical projection areas”, defined as the cortical areas activated by vestibular stimulation, has dramatically increased over the last several years from both anatomical and functional points of view. Four major pathways have been hypothesized to transmit vestibular information to the vestibular cortex: (1) the vestibulo-thalamo-cortical pathway, which probably transmits spatial information about the environment via the parietal, entorhinal and perirhinal cortices to the hippocampus and is associated with spatial representation and self-versus object motion distinctions; (2) the pathway from the dorsal tegmental nucleus via the lateral mammillary nucleus, the anterodorsal nucleus of the thalamus to the entorhinal cortex, which transmits information for estimations of head direction; (3) the pathway via the nucleus reticularis pontis oralis, the supramammillary nucleus and the medial septum to the hippocampus, which transmits information supporting hippocampal theta rhythm and memory; and (4) a possible pathway via the cerebellum, and the ventral lateral nucleus of the thalamus (perhaps to the parietal cortex), which transmits information for spatial learning. Finally a new pathway is hypothesized via the basal ganglia, potentially involved in spatial learning and spatial memory. From these pathways, progressively emerges the anatomical network of vestibular cognition. PMID:25100954

  13. Vestibular pathways involved in cognition.

    PubMed

    Hitier, Martin; Besnard, Stephane; Smith, Paul F

    2014-01-01

    Recent discoveries have emphasized the role of the vestibular system in cognitive processes such as memory, spatial navigation and bodily self-consciousness. A precise understanding of the vestibular pathways involved is essential to understand the consequences of vestibular diseases for cognition, as well as develop therapeutic strategies to facilitate recovery. The knowledge of the "vestibular cortical projection areas", defined as the cortical areas activated by vestibular stimulation, has dramatically increased over the last several years from both anatomical and functional points of view. Four major pathways have been hypothesized to transmit vestibular information to the vestibular cortex: (1) the vestibulo-thalamo-cortical pathway, which probably transmits spatial information about the environment via the parietal, entorhinal and perirhinal cortices to the hippocampus and is associated with spatial representation and self-versus object motion distinctions; (2) the pathway from the dorsal tegmental nucleus via the lateral mammillary nucleus, the anterodorsal nucleus of the thalamus to the entorhinal cortex, which transmits information for estimations of head direction; (3) the pathway via the nucleus reticularis pontis oralis, the supramammillary nucleus and the medial septum to the hippocampus, which transmits information supporting hippocampal theta rhythm and memory; and (4) a possible pathway via the cerebellum, and the ventral lateral nucleus of the thalamus (perhaps to the parietal cortex), which transmits information for spatial learning. Finally a new pathway is hypothesized via the basal ganglia, potentially involved in spatial learning and spatial memory. From these pathways, progressively emerges the anatomical network of vestibular cognition.

  14. 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...

  15. Drug discovery: selecting the optimal approach.

    PubMed

    Sams-Dodd, Frank

    2006-05-01

    The target-based drug discovery approach has for the past 10-15 years been the dominating drug discovery paradigm. However, within the past few years, the commercial value of novel targets in licensing deals has fallen dramatically, reflecting that the probability of reaching a clinical drug candidate for a novel target is very low. This has naturally led to questions regarding the success of target-based drug discovery and, more importantly, a search for alternatives. This paper evaluates the strengths and limitations of the main drug discovery approaches, and proposes a novel approach that could offer advantages for the identification of disease-modifying treatments.

  16. Near-Earth asteroid discovery rate review

    NASA Technical Reports Server (NTRS)

    Helin, Eleanor F.

    1991-01-01

    Fifteen to twenty years ago the discovery of 1 or 2 Near Earth Asteroids (NEAs) per year was typical from one systematic search program, Palomar Planet Crossing Asteroid Survey (PCAS), and the incidental discovery from a variety of other astronomical program. Sky coverage and magnitude were both limited by slower emulsions, requiring longer exposures. The 1970's sky coverage of 15,000 to 25,000 sq. deg. per year led to about 1 NEA discovery every 13,000 sq. deg. Looking at the years from 1987 through 1990, it was found that by comparing 1987/1988 and 1989/1990, the world discovery rate of NEAs went from 20 to 43. More specifically, PCAS' results when grouped into the two year periods, show an increase from 5 discoveries in the 1st period to 20 in the 2nd period, a fourfold increase. Also, the discoveries went from representing about 25 pct. of the world total to about 50 pct. of discoveries worldwide. The surge of discoveries enjoyed by PCAS in particular is attributed to new fine grain sensitive emulsions, film hypering, more uniformity in the quality of the photograph, more equitable scheduling, better weather, and coordination of efforts. The maximum discoveries seem to have been attained at Palomar Schmidt.

  17. 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

  18. 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.

  19. 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.

  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. 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.

  2. Drug discovery from marine microbes.

    PubMed

    Gerwick, William H; Fenner, Amanda M

    2013-05-01

    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 as 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.

  3. The discovery of endogenous retroviruses

    PubMed Central

    Weiss, Robin A

    2006-01-01

    When endogenous retroviruses (ERV) were discovered in the late 1960s, the Mendelian inheritance of retroviral genomes by their hosts was an entirely new concept. Indeed Howard M Temin's DNA provirus hypothesis enunciated in 1964 was not generally accepted, and reverse transcriptase was yet to be discovered. Nonetheless, the evidence that we accrued in the pre-molecular era has stood the test of time, and our hypothesis on ERV, which one reviewer described as 'impossible', proved to be correct. Here I recount some of the key observations in birds and mammals that led to the discovery of ERV, and comment on their evolution, cross-species dispersion, and what remains to be elucidated. PMID:17018135

  4. 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

  5. Advancing drug discovery for schizophrenia

    PubMed Central

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

    2013-01-01

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

  6. Binding Kinetics in Drug Discovery.

    PubMed

    Ferruz, Noelia; De Fabritiis, Gianni

    2016-07-01

    Over the last years, researchers have increasingly become interested in measuring and understanding drugs' binding kinetics, namely the time in which drug and its target associate and dissociate. Historically, drug discovery programs focused on the optimization of target affinity as a proxy of in-vivo efficacy. However, often the efficacy of a ligand is not appropriately described by the in-vitro measured drug-receptor affinity, but rather depends on the lifetime of the in-vivo drug-receptor interaction. In this review we review recent works that highlight the importance of binding kinetics, molecular determinants for rational optimization and the recent emergence of computational methods as powerful tools in measuring and understanding binding kinetics. PMID:27492236

  7. 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

  8. Proteomics Discovery of Disease Biomarkers.

    PubMed

    Ahram, Mamoun; Petricoin, Emanuel F

    2008-01-01

    Recent technological developments in proteomics have shown promising initiatives in identifying novel biomarkers of various diseases. Such technologies are capable of investigating multiple samples and generating large amount of data end-points. Examples of two promising proteomics technologies are mass spectrometry, including an instrument based on surface enhanced laser desorption/ionization, and protein microarrays. Proteomics data must, however, undergo analytical processing using bioinformatics. Due to limitations in proteomics tools including shortcomings in bioinformatics analysis, predictive bioinformatics can be utilized as an alternative strategy prior to performing elaborate, high-throughput proteomics procedures. This review describes mass spectrometry, protein microarrays, and bioinformatics and their roles in biomarker discovery, and highlights the significance of integration between proteomics and bioinformatics.

  9. Cancer gene discovery: exploiting insertional mutagenesis

    PubMed Central

    Ranzani, Marco; Annunziato, Stefano; Adams, David J.; Montini, Eugenio

    2013-01-01

    Insertional mutagenesis has been utilized as a functional forward genetics screen for the identification of novel genes involved in the pathogenesis of human cancers. Different insertional mutagens have been successfully used to reveal new cancer genes. For example, retroviruses (RVs) are integrating viruses with the capacity to induce the deregulation of genes in the neighborhood of the insertion site. RVs have been employed for more than 30 years to identify cancer genes in the hematopoietic system and mammary gland. Similarly, another tool that has revolutionized cancer gene discovery is the cut-and-paste transposons. These DNA elements have been engineered to contain strong promoters and stop cassettes that may function to perturb gene expression upon integration proximal to genes. In addition, complex mouse models characterized by tissue-restricted activity of transposons have been developed to identify oncogenes and tumor suppressor genes that control the development of a wide range of solid tumor types, extending beyond those tissues accessible using RV-based approaches. Most recently, lentiviral vectors (LVs) have appeared on the scene for use in cancer gene screens. LVs are replication defective integrating vectors that have the advantage of being able to infect non-dividing cells, in a wide range of cell types and tissues. In this review, we describe the various insertional mutagens focusing on their advantages/limitations and we discuss the new and promising tools that will improve the insertional mutagenesis screens of the future. PMID:23928056

  10. Gatekeeper discovery mechanism for H.323 systems

    NASA Astrophysics Data System (ADS)

    Sengodan, Senthil

    1999-01-01

    Multimedia communications over packet switched networks - commonly referred to as Internet telephony - has generated immense interest in recent years. The International Telecommunication Union is currently developing the H.323 umbrella of standards for this purpose. In the H-323 standard, a gatekeeper is a control entity that performs functions such as address translation, bandwidth management etc. A H.323 terminal needs to discover a suitable gatekeeper and register with it. When a H.3232 terminal wishes to call another H.323 terminal, communication between the gatekeepers result in the determination of the transport layer address of the destination terminal for sending the connection setup message to. There is thus a need not only for terminals to discover gatekeepers but also for gatekeepers to discover other gatekeepers. In this paper, we propose a mechanism whereby terminals and gatekeepers can discover other gatekeepers. The proposed mechanisms result in efficient use of network bandwidth within the administrative domain. The security issues involved in such communications are discussed, and a proposal is made to establish a shared secret during the discovery process. Such a shared secret may be used for subsequent confidentiality or authentication of messages.

  11. 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.

  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. STS-121: Discovery Mission Overview Briefing

    NASA Technical Reports Server (NTRS)

    2006-01-01

    Tony Ceccacci, Lead STS-121 Space Shuttle Flight director, and Rick LaBrode, Lead STS-121 ULF 1.1 International Space Station Flight Director, are shown in this STS-121 Discovery mission overview. Ceccacci begins with an overview of the mission and gives the mission goals. He also presents various slides of the STS-121 payload that includes: 1) Orbiter Docking System; 2) Integrated Cargo Carrier (ICC); 3) Multipurpose Logistics Module (MPLM); 4) TPS Sample Box Assembly; 5) Shuttle Remote Manipulator System (SRMS); and 6) Orbiter Boom Sensor System (OBSS). He shows a video presentation on the various processes involved in the inspections of the Orbiter that include: 1) Unberthing OBSS; 2) Starboard wing leading edge survey; 3) Wing leading edge passes; 4) Nose cap surveys; 5) Port side surveys; and 6) Docking with the International Space Station. Ceccacci ends his presentation with discussing the work performed from flight day 1 to flight day 14. Rick LaBrode begins with discussing the on-orbit status of the Expedition 13 crew. He then presents a video of the MPLM installation, forward hatch of MPLM, resupply stowage platform, resupply stowage racks, and Oxygen Generator System (OGS) rack. Questions are answered from the media.

  14. 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

  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. 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.…

  17. Discovery of causal mechanisms: Oxidative phosphorylation and the Calvin-Benson cycle.

    PubMed

    Scholl, Raphael; Nickelsen, Kärin

    2015-06-01

    We investigate the context of discovery of two significant achievements of twentieth century biochemistry: the chemiosmotic mechanism of oxidative phosphorylation (proposed in 1961 by Peter Mitchell) and the dark reaction of photosynthesis (elucidated from 1946 to 1954 by Melvin Calvin and Andrew A. Benson). The pursuit of these problems involved discovery strategies such as the transfer, recombination and reversal of previous causal and mechanistic knowledge in biochemistry. We study the operation and scope of these strategies by careful historical analysis, reaching a number of systematic conclusions: (1) even basic strategies can illuminate "hard cases" of scientific discovery that go far beyond simple extrapolation or analogy; (2) the causal-mechanistic approach to discovery permits a middle course between the extremes of a completely substrate-neutral and a completely domain-specific view of scientific discovery; (3) the existing literature on mechanism discovery underemphasizes the role of combinatorial approaches in defining and exploring search spaces of possible problem solutions; (4) there is a subtle interplay between a fine-grained mechanistic and a more coarse-grained causal level of analysis, and both are needed to make discovery processes intelligible. PMID:26013645

  18. Discovery of causal mechanisms: Oxidative phosphorylation and the Calvin-Benson cycle.

    PubMed

    Scholl, Raphael; Nickelsen, Kärin

    2015-06-01

    We investigate the context of discovery of two significant achievements of twentieth century biochemistry: the chemiosmotic mechanism of oxidative phosphorylation (proposed in 1961 by Peter Mitchell) and the dark reaction of photosynthesis (elucidated from 1946 to 1954 by Melvin Calvin and Andrew A. Benson). The pursuit of these problems involved discovery strategies such as the transfer, recombination and reversal of previous causal and mechanistic knowledge in biochemistry. We study the operation and scope of these strategies by careful historical analysis, reaching a number of systematic conclusions: (1) even basic strategies can illuminate "hard cases" of scientific discovery that go far beyond simple extrapolation or analogy; (2) the causal-mechanistic approach to discovery permits a middle course between the extremes of a completely substrate-neutral and a completely domain-specific view of scientific discovery; (3) the existing literature on mechanism discovery underemphasizes the role of combinatorial approaches in defining and exploring search spaces of possible problem solutions; (4) there is a subtle interplay between a fine-grained mechanistic and a more coarse-grained causal level of analysis, and both are needed to make discovery processes intelligible.

  19. 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.

  20. 42 CFR 430.86 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Discovery. 430.86 Section 430.86 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... objection to discovery action initiated under this section. The presiding officer also has the power...

  1. 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…

  2. 37 CFR 42.51 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Discovery. 42.51 Section 42.51 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF... Production § 42.51 Discovery. (a) Mandatory initial disclosures. (1) With agreement. Parties may agree...

  3. 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...

  4. 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...

  5. 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...

  6. 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... 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...

  7. 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…

  8. 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.

  9. 47 CFR 65.105 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 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)...

  10. 47 CFR 65.105 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 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)...

  11. 47 CFR 65.105 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 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)...

  12. 47 CFR 65.105 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 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)...

  13. 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)...

  14. 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....

  15. 12 CFR 263.53 - Discovery depositions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Discovery depositions. 263.53 Section 263.53 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM... proceeding that are not protected from discovery by any applicable privilege, and of identified...

  16. 12 CFR 263.53 - Discovery depositions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Discovery depositions. 263.53 Section 263.53 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM... proceeding that are not protected from discovery by any applicable privilege, and of identified...

  17. 21 CFR 17.23 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Discovery. 17.23 Section 17.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES HEARINGS § 17.23 Discovery. (a) No later than 60 days prior to the hearing, unless otherwise ordered by...

  18. 21 CFR 17.23 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Discovery. 17.23 Section 17.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES HEARINGS § 17.23 Discovery. (a) No later than 60 days prior to the hearing, unless otherwise ordered by...

  19. 21 CFR 17.23 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Discovery. 17.23 Section 17.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES HEARINGS § 17.23 Discovery. (a) No later than 60 days prior to the hearing, unless otherwise ordered by...

  20. 21 CFR 17.23 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Discovery. 17.23 Section 17.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES HEARINGS § 17.23 Discovery. (a) No later than 60 days prior to the hearing, unless otherwise ordered by...

  1. 21 CFR 17.23 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Discovery. 17.23 Section 17.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL CIVIL MONEY PENALTIES HEARINGS § 17.23 Discovery. (a) No later than 60 days prior to the hearing, unless otherwise ordered by...

  2. 49 CFR 1121.2 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... procedures set forth at 49 CFR part 1114, subpart B. Discovery may begin upon the filing of the petition for exemption or petition for revocation of an exemption. In petitions to revoke an exemption, a party must... requests at the same time it files its petition to revoke. Discovery shall be completed 30 days after...

  3. Discovery of Cadmium, Indium, and Tin Isotopes

    NASA Astrophysics Data System (ADS)

    Amos, Stephanie; Thoennessen, Michael

    2009-10-01

    As of today, no comprehensive study has been made covering the initial observations and identifications of isotopes. A project has been undertaken at MSU to document the discovery of all the known isotopes. The criteria defining discovery of a given isotope is the publication of clear mass and element assignment in a refereed journal. Prior to the current work the documentation of the discovery of eleven elements had been completed^1. These elements are cerium^2, arsenic, gold, tungsten, krypton, silver, vanadium, einsteinium, iron, barium, and cobalt. We will present the new documentation for the cadmium, indium, and tin isotopes. Thirty-seven cadmium isotopes, thirty-eight indium isotopes, and thirty-eight tin isotopes have been discovered so far. The description for each discovered isotope includes the year of discovery, the article published on the discovery, the article's author, the method of production, the method of identification, and any previous information concerning the isotope discovery. A summary and overview of all ˜500 isotopes documented so far as a function of discovery year, method and place will also be presented. ^1http://www.nscl.msu.edu/˜thoennes/2009/discovery.htm ^2J.Q. Ginepro, J. Snyder, and M. Thoennessen, At. Data Nucl. Data. Tables, in press (2009), doi:10.1016/j.adt.2009.06.002

  4. 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.…

  5. 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...

  6. 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...

  7. 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...

  8. 12 CFR 308.520 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Discovery. 308.520 Section 308.520 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE RULES OF PRACTICE AND PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types...

  9. 12 CFR 308.520 - Discovery.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Discovery. 308.520 Section 308.520 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE RULES OF PRACTICE AND PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types...

  10. 12 CFR 308.520 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Discovery. 308.520 Section 308.520 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE RULES OF PRACTICE AND PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types...

  11. 12 CFR 308.520 - Discovery.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Discovery. 308.520 Section 308.520 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE RULES OF PRACTICE AND PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types...

  12. 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....

  13. 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....

  14. 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....

  15. 37 CFR 2.120 - Discovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Discovery. 2.120 Section 2.120 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Procedure in Inter Partes Proceedings § 2.120 Discovery. (a) In general. (1) Wherever appropriate,...

  16. Human brain evolution: From gene discovery to phenotype discovery

    PubMed Central

    Preuss, Todd M.

    2012-01-01

    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. PMID:22723367

  17. 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. PMID:25666063

  18. 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.

  19. 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.

  20. 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 ...

  1. 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

  2. Affective Involvement Instrument.

    ERIC Educational Resources Information Center

    Lemlech, Johanna K.

    1970-01-01

    The Affective Involvement Instrument (AII) describes and classifies affective involvement in the process of decision-making as it occurs during classroom activities such as role-playing or group discussions. The thirty-celled instrument behaviorizes the six processes involved in decision-making and combines them with the taxonomic levels of the…

  3. 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…

  4. 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.

  5. 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.

  6. 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.

  7. Lysophospholipid receptors in drug discovery

    PubMed Central

    Kihara, Yasuyuki; Mizuno, Hirotaka; Chun, Jerold

    2014-01-01

    Lysophospholipids (LPs), including lysophosphatidic acid (LPA), sphingosine 1-phospate (S1P), lysophosphatidylinositol (LPI), and lysophosphatidylserine (LysoPS), are bioactive lipids that transduce signals through their specific cell-surface G protein-coupled receptors, LPA1–6, S1P1–5, LPI1, and LysoPS1–3, respectively. These LPs and their receptors have been implicated in both physiological and pathophysiological processes such as autoimmune diseases, neurodegenerative diseases, fibrosis, pain, cancer, inflammation, metabolic syndrome, bone formation, fertility, organismal development, and other effects on most organ systems. Advances in the LP receptor field have enabled the development of novel small molecules targeting LP receptors for several diseases. Most notably, fingolimod (FTY720, Gilenya, Novartis), an S1P receptor modulator, became the first FDA-approved medicine as an orally bioavailable drug for treating relapsing forms of multiple sclerosis. This success is currently being followed by multiple, mechanistically related compounds targeting S1P receptor subtypes, which are in various stages of clinical development. In addition, an LPA1 antagonist, BMS-986020 (Bristol-Myers Squibb), is in Phase 2 clinical development for treating idiopathic pulmonary fibrosis, as is a distinct compound, SAR100842 (Sanofi) for the treatment of systemic sclerosis and related fibrotic diseases. This review summarizes the current state of drug discovery in the LP receptor field. PMID:25499971

  8. 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.

  9. 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.

  10. 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. PMID:17186801

  11. 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

  12. 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.

  13. Reinforcement, stereotypy, and rule discovery

    PubMed Central

    Steele, David L.; Hayes, Steven C.; Brownstein, Aaron J.

    1990-01-01

    The effects of reinforced pretraining on subsequent rule discovery were examined with college students as subjects. Levels of behavioral stereotypy observed during reinforced and non-contingent pretraining were compared. During pretraining subjects received reinforcement if they pressed two keys in a particular sequence. During the problem session pressing each key four times was a necessary condition for reinforcement, but each problem had additional different requirements for reinforcement. Subjects were asked to solve the problems by discovering the rule that determined whether or not they received reinforcement. Levels of stereotyped responding during pretraining were equivalent for contingently and non-contingently trained subjects. During the problem session contingently pretrained, non-contingently pretrained, and naive subjects required equal numbers of trials to solve problems and solved the same number of problems. The results suggest that behavioral stereotypy observed in this experimental preparation may be due to repeated exposure to the task. Differences between the results observed in this study and that of Schwartz (1982) and implications for the use of reinforcement procedures in applied settings are discussed. PMID:22477604

  14. 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.

  15. West Nile Virus Drug Discovery

    PubMed Central

    Lim, Siew Pheng; Shi, Pei-Yong

    2013-01-01

    The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development. PMID:24300672

  16. Lysophospholipid receptors in drug discovery.

    PubMed

    Kihara, Yasuyuki; Mizuno, Hirotaka; Chun, Jerold

    2015-05-01

    Lysophospholipids (LPs), including lysophosphatidic acid (LPA), sphingosine 1-phospate (S1P), lysophosphatidylinositol (LPI), and lysophosphatidylserine (LysoPS), are bioactive lipids that transduce signals through their specific cell-surface G protein-coupled receptors, LPA1-6, S1P1-5, LPI1, and LysoPS1-3, respectively. These LPs and their receptors have been implicated in both physiological and pathophysiological processes such as autoimmune diseases, neurodegenerative diseases, fibrosis, pain, cancer, inflammation, metabolic syndrome, bone formation, fertility, organismal development, and other effects on most organ systems. Advances in the LP receptor field have enabled the development of novel small molecules targeting LP receptors for several diseases. Most notably, fingolimod (FTY720, Gilenya, Novartis), an S1P receptor modulator, became the first FDA-approved medicine as an orally bioavailable drug for treating relapsing forms of multiple sclerosis. This success is currently being followed by multiple, mechanistically related compounds targeting S1P receptor subtypes, which are in various stages of clinical development. In addition, an LPA1 antagonist, BMS-986020 (Bristol-Myers Squibb), is in Phase 2 clinical development for treating idiopathic pulmonary fibrosis, as a distinct compound, SAR100842 (Sanofi) for the treatment of systemic sclerosis and related fibrotic diseases. This review summarizes the current state of drug discovery in the LP receptor field. PMID:25499971

  17. 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.

  18. The story of the discovery of heparin and warfarin.

    PubMed

    Wardrop, Douglas; Keeling, David

    2008-06-01

    Heparin and coumarins have been the mainstay of anticoagulant therapy throughout our working lives. As we stand on the threshold of a new era of anticoagulants it is timely to look back upon their discovery and development. Both have fascinating stories to tell. Jay McLean claimed to have discovered heparin whilst a medical student, although this is disputed. The story of warfarin leads us from a mysterious haemorrhagic disease of cattle to the development of a rat poison which became one of the most commonly prescribed drugs in history. Many people were involved in both stories and we owe them all a debt of gratitude. PMID:18355382

  19. The role of serendipity in drug discovery.

    PubMed

    Ban, Thomas A

    2006-01-01

    Serendipity is one of the many factors that may contribute to drug discovery. It has played a role in the discovery of prototype psychotropic drugs that led to modern pharmacological treatment in psychiatry. It has also played a role in the discovery of several drugs that have had an impact on the development of psychiatry. "Serendipity" in drug discovery implies the finding of one thing while looking for something else. This was the case in six of the twelve serendipitous discoveries reviewed in this paper, i.e., aniline purple, penicillin, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine. In the case of three drugs, i.e., potassium bromide, chloral hydrate, and lithium, the discovery was serendipitous because an utterly false rationale led to correct empirical results; and in case of two others, i.e., iproniazid and sildenafil, because valuable indications were found for these drugs which were not initially those sought The discovery of one of the twelve drugs, chlordiazepoxide, was sheer luck. PMID:17117615

  20. 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. PMID:24409953

  1. 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.

  2. Drug Discovery in Academia- the third way?

    PubMed Central

    Frearson, Julie; Wyatt, Paul

    2010-01-01

    As the pharmaceutical industry continues to re-strategise and focus on low-risk, relatively short term gains for the sake of survival, we need to re-invigorate the early stages of drug discovery and rebalance efforts towards novel modes of action therapeutics and neglected genetic and tropical diseases. Academic drug discovery is one model which offers the promise of new approaches and an alternative organisational culture for drug discovery as it attempts to apply academic innovation and thought processes to the challenge of discovering drugs to address real unmet need. PMID:20922062

  3. Recent Advances in Natural Product Discovery

    PubMed Central

    Luo, Yunzi; Cobb, Ryan E.; Zhao, Huimin

    2014-01-01

    Natural products have been and continue to be the source and inspiration for a substantial fraction of human therapeutics. Although the pharmaceutical industry has largely turned its back on natural product discovery efforts, such efforts continue to flourish in academia with promising results. Natural products have traditionally been identified from a top-down perspective, but more recently genomics- and bioinformatics-guided bottom-up approaches have provided powerful alternative strategies. Here we review recent advances in natural product discovery from both angles, including diverse sampling and innovative culturing and screening approaches, as well as genomics-driven discovery and genetic manipulation techniques for both native and heterologous expression. PMID:25260043

  4. 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.

  5. 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.

  6. Engaging the Public in the Discovery of Other Worlds: The Kepler Discovery Mission Education and Public Outreach Program

    NASA Astrophysics Data System (ADS)

    DeVore, E. K.; Gould, A. D.; Harman, P. K.; Koch, D. G.

    2005-12-01

    Are we alone? Are there other worlds like our own? Astronomers are discovering large planets, but can smaller planets - new Earths - be found? These are powerful and exciting questions that motivate student learning and public interest in NASA's Kepler Discovery Mission's search for planets. Continual discoveries of extrasolar planets have sparked broad public interest, and Kepler will expand this search to discover planets like our own. The Kepler Mission Education and Public Outreach (EPO) program focuses on the excitement of discovering Earth-size planets in the habitable zone to enhance student learning and public interest in astronomy and physics. Kepler will launch in 2008, to begin searching for extrasolar Earths. During the first year, we expect Kepler to rapidly detect large planets similar to 51 Peg and smaller Earth-size planets in Mercury-like orbits. By the fourth year, we anticipate the discovery Earth-size planets in habitable zones. The Kepler EPO program began October 2002 and will continue through at least 2012, and our goals and plans are presented in this poster. The EPO program is scoped to build public interest during development, and to engage students and the public throughout the initial four-year, on-orbit mission and beyond if an extended mission is conducted. The EPO goals are to increase public awareness and understanding of the Kepler Mission by embodying key principles of NASA's ``Partners in Education" and ``Implementing the OSS Education/ Public Outreach Strategy:" involve scientists and contractors in EPO efforts, establish collaborations with planetariums and science museums, and build on existing programs and networks that maximize the leverage of NASA EPO funding in this project. The Kepler EPO plan is designed to take advantage of existing collaborations, networks, experience, and relationships to optimize the impact of EPO. Kepler EPO is funded by NASA's Discovery Mission Program, Science Mission Directorate.

  7. 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... discovery action initiated pursuant to this section. The Presiding Officer shall also have the power...

  8. 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...

  9. 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,...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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.

  15. 29 CFR 1603.210 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STATE AND LOCAL GOVERNMENT EMPLOYEE COMPLAINTS OF EMPLOYMENT DISCRIMINATION UNDER SECTION 304 OF THE GOVERNMENT EMPLOYEE RIGHTS ACT OF 1991 Hearings § 1603.210 Discovery. (a) Unless otherwise ordered by...

  16. 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...

  17. 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...

  18. 37 CFR 41.150 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... COMMERCE PRACTICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES Contested Cases § 41.150 Discovery... requested material is in a language other than English, a translation, if available, and (ii) File with...

  19. 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.

  20. 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.

  1. 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

  2. 12 CFR 308.520 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types of... for admission of the authenticity of any relevant document or of the truth of any relevant fact;...

  3. 28 CFR 71.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... (a) The following types of discovery are authorized: (1) Requests for production of documents for... truth of any relevant fact; (3) Written interrogatories; and (4) Depositions. (b) For the purpose...

  4. 22 CFR 35.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) The following types of discovery are authorized: (1) Requests for production of documents for... truth of any relevant fact; (3) Written interrogatories; and (4) Depositions. (b) For the purpose...

  5. 45 CFR 79.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... (a) The following types of discovery are authorized: (1) Requests for production of documents for... or of the truth of any revelant fact; (3) Written interrogatories; and (4) Depositions. (b) For...

  6. 10 CFR 1013.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests for admissions of the authenticity of any relevant document or of the truth of...

  7. 6 CFR 13.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) In general. (1) The following types of discovery are authorized: (i) Requests for production of... Document or of the truth of any relevant fact; (iii) Written interrogatories; and (iv) Depositions....

  8. 34 CFR 33.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... types of discovery are authorized: (1) Requests for production of documents for inspection and copying. (2) Requests for admissions of the authenticity of any relevant document or of the truth of...

  9. 7 CFR 1.322 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Under the Program Fraud Civil Remedies Act of 1986 § 1.322 Discovery. (a) The following types of...) Requests for admission of the authenticity of any relevant document or the truth of any relevant fact;...

  10. 20 CFR 355.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... UNDER THE PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 355.21 Discovery. (a) The following types of... for admissions of the authenticity of any relevant document or of the truth of any relevant fact;...

  11. 40 CFR 164.51 - Other discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) that such information has significant probative value. The Administrative Law Judge shall be guided by... the taking of the discovery, (ii) the nature of the information expected to be discovered and...

  12. 37 CFR 11.52 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., 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...

  13. 29 CFR 1603.210 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... STATE AND LOCAL GOVERNMENT EMPLOYEE COMPLAINTS OF EMPLOYMENT DISCRIMINATION UNDER SECTION 304 OF THE GOVERNMENT EMPLOYEE RIGHTS ACT OF 1991 Hearings § 1603.210 Discovery. (a) Unless otherwise ordered by...

  14. The National Cancer Program: Driving Discovery

    Cancer.gov

    An overview of NCI’s role in driving cancer research discoveries: conducting and funding research in challenging areas and providing resources and leadership to national infrastructures for cancer research.

  15. Priority of discovery in the life sciences.

    PubMed

    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

  16. 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)

  17. 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.

  18. 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...

  19. PTF SN discovery report, April 2012

    NASA Astrophysics Data System (ADS)

    Gal-Yam, Avishay; Arcavi, I.; Ben-Ami, S.; Yaron, O.; Nugent, P.; Levitam, D.; Simonian, G.; Sesar, B.; Cao, Y.; Horesh, A.; Bellm, E.; Silverman, J.; Miller, A.; Cenko, S. B.; Clubb, K. I.; Filippenko, A. V.; Shivvers, I.; Kasliwal, M.; Parrent, J.; Maguire, K.; Pan, Y.-C.

    2012-05-01

    The PTF (ATEL #1964, #3253; http://www.astro.caltech.edu/ptf/; Law et al. 2009, PASP, 121, 1395; Rau et al. 2009, PASP, 121, 1334) reports the discovery of 19 new supernovae. PTF discoveries are made by autonomous PTF software (Bloom et al. 2011, http://adsabs.harvard.edu/abs/2011arXiv1106.5491B ), as well as by the Galaxy Zoo Supernova Project (Smith et al. 2011, MNRAS, 412, 1309; http://supernova.galaxyzoo.org ).

  20. PTF SN discovery report, August 2012

    NASA Astrophysics Data System (ADS)

    Arcavi, Iair; Gal-Yam, A.; Ben-Ami, S.; Yaron, O.; Horesh, P. Nugent A.; Cao, Y.; Bellm, E.; Fynbo, J.; Wiis, J.; Olesen, J.; Engedal, L.; Larsen, A.; Kasliwal, M.; Pan, Y.-C.; Graham, M.; Parrent, J.; Quimby, R.; PTF Team

    2012-08-01

    The PTF (ATEL #1964, #3253; http://www.astro.caltech.edu/ptf; Law et al. 2009, PASP, 121, 1395; Rau et al. 2009, PASP, 121, 1334) reports the discovery of 12 new supernovae. PTF discoveries are made by autonomous PTF software (Bloom et al. 2011, http://adsabs.harvard.edu/abs/2011arXiv1106.5491B ), as well as by the Galaxy Zoo Supernova Project (Smith et al. 2011, MNRAS, 412, 1309; http://supernova.galaxyzoo.org ).

  1. PTF SN discovery report, March 2012

    NASA Astrophysics Data System (ADS)

    Gal-Yam, Avishay; Arcavi, I.; Ben-Ami, S.; Yaron, O.; Nugent, P.; Levitam, D.; Simonian, G.; Sesar, B.; Cao, Y.; Horesh, A.; Bellm, E.; Silverman, J.; Miller, A.; Cenko, S. B.; Clubb, K. I.; Filippenko, A. V.; Shivvers, I.; Kasliwal, M.; Parrent, J.; Maguire, K.; Pan, Y.-C.

    2012-05-01

    The PTF (ATEL #1964, #3253; http://www.astro.caltech.edu/ptf/; Law et al. 2009, PASP, 121, 1395; Rau et al. 2009, PASP, 121, 1334) reports the discovery of 26 new supernovae. PTF discoveries are made by autonomous PTF software (Bloom et al. 2011, http://adsabs.harvard.edu/abs/2011arXiv1106.5491B ), as well as by the Galaxy Zoo Supernova Project (Smith et al. 2011, MNRAS, 412, 1309; http://supernova.galaxyzoo.org ).

  2. PTF SN discovery report, July 2012

    NASA Astrophysics Data System (ADS)

    Gal-Yam, Avishay; Ben-Ami, Sagi; Arcavi, I.; Yaron, O.; Nugent, Peter; Sesar, B.; Cao, Y.; Silverman, J.; Clubb, K.; Filippenko, A. V.; Cenko, S. B.; Parrent, J.; Maguire, K.; Sullivan, M.

    2012-08-01

    The PTF (ATEL #1964, #3253; http://www.astro.caltech.edu/ptf/ ; Law et al. 2009, PASP, 121, 1395; Rau et al. 2009, PASP, 121, 1334) reports the discovery of 14 new supernovae. PTF discoveries are made by autonomous PTF software (Bloom et al. 2011, http://adsabs.harvard.edu/abs/2011arXiv1106.5491B ), as well as by the Galaxy Zoo Supernova Project (Smith et al. 2011, MNRAS, 412, 1309; http://supernova.galaxyzoo.org ).

  3. PTF SN discovery report, July 2012

    NASA Astrophysics Data System (ADS)

    Gal-Yam, Avishay; Ben-Ami, Sagi; Yaron, O.; Arcavi, I.; Nugent, Peter; Levitan, D.; Perley, D.; Kulkarni, S. R.; Sesar, B.; Cao, Y.; Bellm, E.; Barlow, T.; Silverman, J.; Clubb, K.; Miller, A.; Fox, O.; Pan, Y.-C.; Maguire, K.; Sullvan, M.; Walker, E.; Kasliwal, M.; Graham, M.; Parrent, J.

    2012-07-01

    The PTF (ATEL #1964, #3253; http://www.astro.caltech.edu/ptf/ ; Law et al. 2009, PASP, 121, 1395; Rau et al. 2009, PASP, 121, 1334) reports the discovery of 20 new supernovae. PTF discoveries are made by autonomous PTF software (Bloom et al. 2011, http://adsabs.harvard.edu/abs/2011arXiv1106.5491B ), as well as by the Galaxy Zoo Supernova Project (Smith et al. 2011, MNRAS, 412, 1309; http://supernova.galaxyzoo.org ).

  4. PTF SN discovery report, September 8, 2012

    NASA Astrophysics Data System (ADS)

    Gal-Yam, A.; Nugent, P.; Walker, E.; Cenko, S. B.; Fox, O.

    2012-09-01

    The PTF (ATEL #1964, #3253; http://www.astro.caltech.edu/ptf ; Law et al. 2009, PASP, 121, 1395; Rau et al. 2009, PASP, 121, 1334) reports the discovery of 8 new supernovae. PTF discoveries are made by autonomous PTF software (Bloom et al. 2011, http://adsabs.harvard.edu/abs/2011arXiv1106.5491B ), as well as by the Galaxy Zoo Supernova Project (Smith et al. 2011, MNRAS, 412, 1309; http://supernova.galaxyzoo.org ).

  5. PTF SN discovery report, October 9, 2012

    NASA Astrophysics Data System (ADS)

    Gal-Yam, A.; Nugent, P.; Cao, Y.; Levitan, D.; Hallinan, G.; Kyne, G.; Silverman, J.; Clubb, K.; Miller, A.; Fox, O.; Suzuki, N.; Quimby, R.

    2012-10-01

    The PTF (ATEL #1964, #3253; http://www.astro.caltech.edu/ptf; Law et al. 2009, PASP, 121, 1395; Rau et al. 2009, PASP, 121, 1334) reports the discovery of 9 new supernovae. PTF discoveries are made by autonomous PTF software (Bloom et al. 2011, http://adsabs.harvard.edu/abs/2011arXiv1106.5491B ), as well as by the Galaxy Zoo Supernova Project (Smith et al. 2011, MNRAS, 412, 1309; http://supernova.galaxyzoo.org ).

  6. 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.

  7. UK now claims world's top discovery rate

    SciTech Connect

    Not Available

    1985-05-01

    UK explorers are a bit more cheerful these days even though no one has discovered a giant field or anything elephant-sized. The reason is a benign tax regime and a growing confidence among industry explorers. This last has resulted in discovery of many smaller fields - particularly gas, some potentially commercial. It is claimed that the UK's discovery rate is now the highest in the world.

  8. The Collaborative Drug Discovery (CDD) database.

    PubMed

    Ekins, Sean; Bunin, Barry A

    2013-01-01

    The broad goals of Collaborative Drug Discovery (CDD) are to enable a collaborative "cloud-based" tool to be used to bring together neglected disease researchers and other researchers from usually separate areas, to collaborate and to share compounds and drug discovery data in the research community, which will ultimately result in long-term improvements in the research enterprise and health care delivery. This chapter briefly introduces CDD software and describes applications in antimalarial and tuberculosis research. PMID:23568469

  9. 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.

  10. History of the Discovery of Mira Stars

    NASA Astrophysics Data System (ADS)

    Hoffleit, Dorrit

    This year we celebrate the 400th anniversary of Fabricius' discovery of Mira, "The Wonderful," in 1596. But was he the first? Within the first century following Fabricius, four Mira-type variables were discovered, and in all cases it has been found that the stars were suspected of being novae long before their "official" discovery in the Western World. Three of the four had been recorded as novae in early Chinese or Korean records. By 1896, 251 Mira-type variabes had been discovered, most of them after the beginning of photographic experimentation. Now in the year of the fourth centennial, over 6000 Miras are known. Because of their ease of discovery relative to stars of small amplitude, no new Mira stars reaching naked-eye visibility have been discovered since 1899. The history of the discovery of Mira-type variables illustrates that (1) some new discoveries are re-discoveries of objects previously assumed to be novae; and (2) apparently logical deductions that early observations of a guest star correspond to a later discovered Mire-type may nevertheless be wrong.

  11. Evaluation of Literature-Based Discovery Systems

    NASA Astrophysics Data System (ADS)

    Yetisgen-Yildiz, M.; Pratt, W.

    Evaluating discovery systems is a fundamentally challenging task because if they are successful, by definition they are capturing new knowledge that has yet to be proven useful. To overcome this difficulty, many researchers in literature-based discovery (LBD) replicated Swanson's discoveries to evaluate the performance of their systems. They reported overall success if one of the discoveries generated by their system was the same as Swanson's discovery. This type of evaluation is powerful yet incomplete because it does not inform us about the quality of the rest of the discoveries identified by the system nor does it test the generalizability of the results. Recently, alternative evaluation methods have been designed to provide more information on the overall performance of the systems. The purpose of this chapter is to review and analyze the current evaluation methods for LBD systems and to discuss potential ways to use these evaluation methods for comparing performance of different systems, rather than reporting the performance of only one system. We will also summarize the current approaches used to evaluate the graphical user interfaces of LBD systems.

  12. Looking at Multimedia: Design Issues in Several Discovery-Oriented Programs. Technical Report No. 13.

    ERIC Educational Resources Information Center

    Wilson, Kathleen; Tally, William

    Based on reviews of 10 examples of multimedia design, this paper presents an introductory framework for reflecting on the issues involved in the design of interactive multimedia instructional programs for discovery learning. High school students, junior and senior high school teachers, and Center for Technology in Education (CTE) staff reviewed…

  13. 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.

  14. Discovery Maps: A Student-Centered Approach To Reinforcing the Curriculum.

    ERIC Educational Resources Information Center

    Chase, Patricia A.; Franson, Kari L.; An, Ariane

    2001-01-01

    Describes a project which involved first- and second-year pharmacy students in making Discovery Maps focused on specific diseases. The maps were intended to help students remember and relate key pieces of information from all their courses. Feedback from students and faculty was very positive. (EV)

  15. 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…

  16. Glial Cells are Involved in Itch Processing.

    PubMed

    Andersen, Hjalte H; Arendt-Nielsen, Lars; Gazerani, Parisa

    2016-08-23

    Recent discoveries in itch neurophysiology include itch-selective neuronal pathways, the clinically relevant non-histaminergic pathway, and elucidation of the notable similarities and differences between itch and pain. Potential involvement of glial cells in itch processing and the possibility of glial modulation of chronic itch have recently been identified, similarly to the established glial modulation of pain processing. This review outlines the similarities and differences between itch and pain, and how different types of central and peripheral glial cells may be differentially involved in the development of chronic itch akin to their more investigated role in chronic pain. Improvements are needed in the management of chronic itch, and future basic and interventional studies on glial activity modulation would both enhance our understanding of mechanisms underlying the chronification of itch and provide novel opportunities for the prevention or treatment of this debilitating and common condition.

  17. 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.

  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. PMID:24853975

  19. 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 an…

  20. Building Parent Involvement

    ERIC Educational Resources Information Center

    Nelson, Richard C.; Bloom, John W.

    1973-01-01

    Discussed is the rationale behind parent involvement in guidance and educational activities, together with specific suggestions for involving parents with other adults (parent advisory committees, informal coffees, Transactional analysis (groups etc.), with children (story hours, trips, demonstrations, counseling booths, testing, interviewing,…

  1. Parent Involvement Handbook.

    ERIC Educational Resources Information Center

    Caplan, Arna

    This handbook on parent involvement, designed to be used with preschool programs, was developed by the Jefferson County Public Schools in Lakewood, Colorado. Included are: (1) a general statement about parent involvement in an early childhood program, (2) a description of the Jefferson County Early Childhood Program, (3) a description of the…

  2. 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…

  3. 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…

  4. Rational discovery of dengue type 2 non-competitive inhibitors.

    PubMed

    Heh, Choon H; Othman, Rozana; Buckle, Michael J C; Sharifuddin, Yusrizam; Yusof, Rohana; Rahman, Noorsaadah A

    2013-07-01

    Various works have been carried out in developing therapeutics against dengue. However, to date, no effective vaccine or anti-dengue agent has yet been discovered. The development of protease inhibitors is considered as a promising option, but most previous works have involved competitive inhibition. In this study, we focused on rational discovery of potential anti-dengue agents based on non-competitive inhibition of DEN-2 NS2B/NS3 protease. A homology model of the DEN-2 NS2B/NS3 protease (using West Nile Virus NS2B/NS3 protease complex, 2FP7, as the template) was used as the target, and pinostrobin, a flavanone, was used as the standard ligand. Virtual screening was performed involving a total of 13 341 small compounds, with the backbone structures of chalcone, flavanone, and flavone, available in the ZINC database. Ranking of the resulting compounds yielded compounds with higher binding affinities compared with the standard ligand. Inhibition assay of the selected top-ranking compounds against DEN-2 NS2B/NS3 proteolytic activity resulted in significantly better inhibition compared with the standard and correlated well with in silico results. In conclusion, via this rational discovery technique, better inhibitors were identified. This method can be used in further work to discover lead compounds for anti-dengue agents.

  5. 4 CFR 28.42 - Discovery procedures and protective orders.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 4 Accounts 1 2012-01-01 2012-01-01 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...

  6. 4 CFR 28.42 - Discovery procedures and protective orders.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 4 Accounts 1 2011-01-01 2011-01-01 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...

  7. 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...

  8. 18 CFR 385.908 - Discovery (Rule 908).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... conduct discovery where such discovery relates to new facts or issues raised in accordance with Rule 907(b... discovery: (1) Relates to new facts or issues raised in accordance with Rule 907(c) (new facts and issues... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Discovery (Rule...

  9. Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta

    PubMed Central

    Jiang, Lin; Liu, Cong; Leibly, David; Landau, Meytal; Zhao, Minglei; Hughes, Michael P; Eisenberg, David S

    2013-01-01

    Amyloid protein aggregates are associated with dozens of devastating diseases including Alzheimer’s, Parkinson’s, ALS, and diabetes type 2. While structure-based discovery of compounds has been effective in combating numerous infectious and metabolic diseases, ignorance of amyloid structure has hindered similar approaches to amyloid disease. Here we show that knowledge of the atomic structure of one of the adhesive, steric-zipper segments of the amyloid-beta (Aβ) protein of Alzheimer’s disease, when coupled with computational methods, identifies eight diverse but mainly flat compounds and three compound derivatives that reduce Aβ cytotoxicity against mammalian cells by up to 90%. Although these compounds bind to Aβ fibers, they do not reduce fiber formation of Aβ. Structure-activity relationship studies of the fiber-binding compounds and their derivatives suggest that compound binding increases fiber stability and decreases fiber toxicity, perhaps by shifting the equilibrium of Aβ from oligomers to fibers. DOI: http://dx.doi.org/10.7554/eLife.00857.001 PMID:23878726

  10. 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

  11. Reporting Astronomical Discoveries: Past, Now, and Future

    NASA Astrophysics Data System (ADS)

    Yamaoka, Hitoshi; Green, Daniel W. E.; Samus, Nikolai N.; West, Richard

    2015-08-01

    Many new astronomical objects have been discovered over the years by amateur astronomers, and this continues to be the case. They have traditionally reported them (as have professional astronomers) to the Central Bureau for Astronomical Telegrams (CBAT), which was established in the 19th century. This procedure has worked very well throughout the 20th century, moving under the umbrella of the newly established IAU in 1920. The discoverers have been honored by the formal announcement of their discoveries in the publications of the CBAT.In recent years, some professional research groups have established other ways of announcing their discoveries of explosive objects such as novae and supernovae; some do not now report their discoveries or spectroscopic confirmations of the transients to the CBAT, including often spectroscopic reports of objects posted to the CBAT "Transient Objects Confirmation Page" -- the highly successful TOCP webpage, which assigns official positional designations to new transients posted there by approved, registered users. This leads to a delay in formal announcements of discoveries by amateur astronomers in many cases, as well as inconsistent designations being put into use by individual groups. Amateur astronomers are feeling frustrated about this situation, and they hope that the IAU will help to settle the situation.We have proposed the new IAU commission NC-52, which will treat these phenomena in a continuation of Commission 6, through the CBAT. We hope to continuously support the reporting of the discoveries by amateur astronomers, as well as professional astronomers, who all deserve and desire proper recognition. Our strategy will maintain the firm trust between the amateur and professional astronomers, which is necessary for true collaboration. The plan is for the CBAT to work with collaborators to assure that discoveries posted on the TOCP are promptly designated and announced by the CBAT, even when confirmations are made elsewhere

  12. Eye Involvement in TSC

    MedlinePlus

    ... what we see to the brain via the optic nerve. Retinal and optic nerve involvement in TSC are well known today, ... hamartomas (non-cancerous tumors) of the retina or optic nerve. The most common type of retinal hamartoma ...

  13. Novel cell lines promote the discovery of genes involved in early heart development.

    PubMed

    Brunskill, E W; Witte, D P; Yutzey, K E; Potter, S S

    2001-07-15

    Clonal cell lines representing early cardiomyocytes would provide valuable reagents for the dissection of the genetic program of early cardiogenesis. Here we describe the establishment and characterization of cell lines from the hearts of transgenic mice and embryos with SV40 large T antigen expressed in the heart-forming region. Ultrastructure analysis by transmission electron microscopy showed the primitive, precontractile nature of the resulting cells, with the absence of myofilaments, Z lines, and intercalated disks. Immunohistochemistry, RT-PCR, Northern blots, and oligonucleotide microarrays were used to determine the expression levels of thousands of genes in the 1H and ECL-2 cell lines. The resulting gene-expression profiles showed the transcription of early cardiomyocyte genes such as Nkx2.5, GATA4, Tbx5, dHAND, cardiac troponin C, and SM22-alpha. Furthermore, many genes not previously implicated in early cardiac development were expressed. Two of these genes, Hic-5, a possible negative regulator of muscle differentiation, and the transcription enhancing factor TEF-5 were selected and shown by in situ hybridizations to be expressed in the early developing heart. The results show that the 1H and ECL-2 cell lines can be used to discover novel genes expressed in the early cardiomyocyte. PMID:11437454

  14. Discovery of a novel enzyme, isonitrile hydratase, involved in nitrogen-carbon triple bond cleavage.

    PubMed

    Goda, M; Hashimoto, Y; Shimizu, S; Kobayashi, M

    2001-06-29

    Isonitrile containing an N triple bond C triple bond was degraded by microorganism sp. N19-2, which was isolated from soil through a 2-month acclimatization culture in the presence of this compound. The isonitrile-degrading microorganism was identified as Pseudomonas putida. The microbial degradation was found to proceed through an enzymatic reaction, the isonitrile being hydrated to the corresponding N-substituted formamide. The enzyme, named isonitrile hydratase, was purified and characterized. The native enzyme had a molecular mass of about 59 kDa and consisted of two identical subunits. The enzyme stoichiometrically catalyzed the hydration of cyclohexyl isocyanide (an isonitrile) to N-cyclohexylformamide, but no formation of other compounds was detected. The apparent K(m) value for cyclohexyl isocyanide was 16.2 mm. Although the enzyme acted on various isonitriles, no nitriles or amides were accepted as substrates.

  15. 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

  16. 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…

  17. 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…

  18. REDOR NMR for Drug Discovery

    PubMed Central

    Cegelski, Lynette

    2014-01-01

    Rotational-Echo DOuble-Resonance (REDOR) NMR is a powerful and versatile solid-state NMR measurement that has been recruited to elucidate drug modes of action and to drive the design of new therapeutics. REDOR has been implemented to examine composition, structure, and dynamics in diverse macromolecular and whole-cell systems, including taxol-bound microtubules, enzyme-cofactor-inhibitor ternary complexes, and antibiotic-whole-cell complexes. The REDOR approach involves the integrated design of specific isotopic labeling strategies and the selection of appropriate REDOR experiments. By way of example, this digest illustrates the versatility of the REDOR approach, with an emphasis on the practical considerations of experimental design and data interpretation. PMID:24035486

  19. 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.

  20. 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.

  1. Using C. elegans for antimicrobial drug discovery

    PubMed Central

    Desalermos, Athanasios; Muhammed, Maged; Glavis-Bloom, Justin; Mylonakis, Eleftherios

    2011-01-01

    Introduction The number of microorganism strains with resistance to known antimicrobials is increasing. Therefore, there is a high demand for new, non-toxic and efficient antimicrobial agents. Research with the microscopic nematode Caenorhabditis elegans can address this high demand for the discovery of new antimicrobial compounds. In particular, C. elegans can be used as a model host for in vivo drug discovery through high-throughput screens of chemical libraries. Areas covered This review introduces the use of substitute model hosts and especially C. elegans in the study of microbial pathogenesis. The authors also highlight recently published literature on the role of C. elegans in drug discovery and outline its use as a promising host with unique advantages in the discovery of new antimicrobial drugs. Expert opinion C. elegans can be used, as a model host, to research many diseases, including fungal infections and Alzheimer’s disease. In addition, high-throughput techniques, for screening chemical libraries, can also be facilitated. Nevertheless, C. elegans and mammals have significant differences that both limit the use of the nematode in research and the degree by which results can be interpreted. That being said, the use of C. elegans in drug discovery still holds promise and the field continues to grow, with attempts to improve the methodology already underway. PMID:21686092

  2. 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. PMID:24788267

  3. [Orbitotemporal facial involvement in type 1 neurofibromatosis (NF1)].

    PubMed

    Rilliet, B; Pittet, B; Montandon, D; Narata, A-P; de Ribaupierre, S; Schils, F; Boscherini, D; Di Rocco, C; Ducrey, N

    2010-01-01

    Plexiform neurofibromas of the orbit, sometimes extending to the temporal region and the face, are considered to be a rare but devastating and disfiguring complication of neurofibromatosis type 1. The first symptoms appear in infancy and the involvement of the orbit and the face is present in nearly all children after the age of 5. The disease is unilateral in most cases but can exceptionally involve both sides of the face. Progressive deformation of the orbital frame due to the expanding plexiform neurofibroma and buphthalmos occurs in a large proportion of cases. The associated sphenoidal dysplasia, which is thought to be, according to the most recent hypothesis, genetically determined, will inescapably increase the burden to the orbital content, cause pulsating proptosis and will endanger noble structures, finally resulting in loss of vision. Using the Jackson classification, the authors report their personal series of 22 cases (19 operated). Until now, there has been no effective medical treatment for plexiform neurofibroma and surgery remains the standard care for these patients. Controversies remain about the timing of the first operation and today most multidisciplinary teams involving plastic, maxillofacial, ophthalmologic, and neurosurgeons favor early intervention to try to minimize the secondary deformation of the orbital and facial skeleton. A number of cases of plexiform neurofibromas are illustrated within the three Jackson groups and treatment results of the rare elephantiasis neuromatosa cases are presented. Special techniques such as preoperative embolization of heavily vascularized plexiform neurofibroma are also discussed.

  4. [Pulmonary involvements of sarcoidosis].

    PubMed

    Ohmichi, M; Hiraga, Y; Hirasawa, M

    1990-01-01

    We reported about intrathoracic changes and prognosis of 686 patients with sarcoidosis diagnosed in our hospital between 1963 and 1988. We evaluated CT findings in 135 patients with sarcoidosis and found pulmonary involvements in 81. We analyzed CT findings according to the classification by Tuengerthal which classified radiographic findings combining ILO classification of pneumoconiosis and characteristic findings of bronchovascular sheath with sarcoidosis. The CT findings were as follows: small opacities (44 out of 81 cases, 54.3%), large opacities (37 cases, 46.7%). Additional findings were as follows: peribronchial marking (42 cases, 51.9%), contraction (17 cases, 21.0%), pleural involvement (9 cases, 11.1%), bulla (5 cases, 6.2%). The characteristic CT findings of serious sarcoidosis were extasis of bronchus, thickening of the bronchial wall, unclearness of vascular shadow, atelectasis and thickening of pleura. Concerning the prognosis of pulmonary involvement, according to age, patients younger than 30 years old at initial diagnosis were better than those of 30 years and over in terms of disappearance of pulmonary involvements. According to stage, patients of stage I and stage II were better than those of stage III. Among the patients we were able to observe chest X-ray findings during five years according to the character of shadow, ill-defined shadow of small opacities and rounded shadows of large opacities had a higher disappearance rate of pulmonary involvements than irregular shadows of large opacities, atelectasis and contraction.

  5. Musculoskeletal involvement in sarcoidosis*, **

    PubMed Central

    Nessrine, Akasbi; Zahra, Abourazzak Fatima; Taoufik, Harzy

    2014-01-01

    Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis), and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-α, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management. PMID:24831403

  6. 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.

  7. Penicillin: its discovery and early development.

    PubMed

    Ligon, B Lee

    2004-01-01

    In August 1928, Alexander Fleming returned from a vacation to his usually messy, disordered laboratory. In one of the Petri dishes that had not been touched by the Lysol, he noticed an unusual phenomenon: separate colonies of staphylococci and, near the dish's edge, a colony of mold approximately 20 mm in diameter. The finding proved to be a watershed in the history of medicine. This discovery lay dormant for some time before other researchers took up the challenge to investigate its clinical possibilities. Two investigators at Oxford, Sir Howard Walter Florey and Ernst Boris Chain, brought penicillin's potential for medical use to fruition and, along with Fleming, shared the 1945 Nobel Prize for Medicine. The discovery and development of penicillin represent one of the most important developments in the annals of medical history. This article presents a brief overview of the events that occurred in the progress from discovery to implementation as a therapeutic agent. PMID:15175995

  8. 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.

  9. 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

  10. 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

  11. Intercellular Lipid Mediators and GPCR Drug Discovery

    PubMed Central

    Im, Dong-Soon

    2013-01-01

    G-protein-coupled receptors (GPCR) are the largest superfamily of receptors responsible for signaling between cells and tissues, and because they play important physiological roles in homeostasis, they are major drug targets. New technologies have been developed for the identification of new ligands, new GPCR functions, and for drug discovery purposes. In particular, intercellular lipid mediators, such as, lysophosphatidic acid and sphingosine 1-phosphate have attracted much attention for drug discovery and this has resulted in the development of fingolimod (FTY-720) and AM095. The discovery of new intercellular lipid mediators and their GPCRs are discussed from the perspective of drug development. Lipid GPCRs for lysophospholipids, including lysophosphatidylserine, lysophosphatidylinositol, lysophosphatidylcholine, free fatty acids, fatty acid derivatives, and other lipid mediators are reviewed. PMID:24404331

  12. Penicillin: its discovery and early development.

    PubMed

    Ligon, B Lee

    2004-01-01

    In August 1928, Alexander Fleming returned from a vacation to his usually messy, disordered laboratory. In one of the Petri dishes that had not been touched by the Lysol, he noticed an unusual phenomenon: separate colonies of staphylococci and, near the dish's edge, a colony of mold approximately 20 mm in diameter. The finding proved to be a watershed in the history of medicine. This discovery lay dormant for some time before other researchers took up the challenge to investigate its clinical possibilities. Two investigators at Oxford, Sir Howard Walter Florey and Ernst Boris Chain, brought penicillin's potential for medical use to fruition and, along with Fleming, shared the 1945 Nobel Prize for Medicine. The discovery and development of penicillin represent one of the most important developments in the annals of medical history. This article presents a brief overview of the events that occurred in the progress from discovery to implementation as a therapeutic agent.

  13. Virtual drug discovery: beyond computational chemistry?

    PubMed

    Gilardoni, Francois; Arvanites, Anthony C

    2010-02-01

    This editorial looks at how a fully integrated structure that performs all aspects in the drug discovery process, under one company, is slowly disappearing. The steps in the drug discovery paradigm have been slowly increasing toward virtuality or outsourcing at various phases of product development in a company's candidate pipeline. Each step in the process, such as target identification and validation and medicinal chemistry, can be managed by scientific teams within a 'virtual' company. Pharmaceutical companies to biotechnology start-ups have been quick in adopting this new research and development business strategy in order to gain flexibility, access the best technologies and technical expertise, and decrease product developmental costs. In today's financial climate, the term virtual drug discovery has an organizational meaning. It represents the next evolutionary step in outsourcing drug development.

  14. Accelerating the Rate of Astronomical Discovery

    NASA Astrophysics Data System (ADS)

    This meeting marks the the International Year of Astronomy by reviewing the extent to which astronomers are achieving the optimal rate of astronomical discovery. Can we identify and overcome the limits to progress? What steps can be taken to accelerate the rate of expansion of astronomical knowledge? What lessons can be learnt both from the recent and distant past? As the public announcements regarding the 2009 IYA have emphasized, new astronomical discoveries are currently being made at an extraordinary rate, while the invention of the telescope ushered in an equally momentous "golden age of discovery" 400 years ago. The meeting addresses a range of potential limits to progress-paradigmatic, technological, organizational, and political-examining each issue both from modern and historical perspectives, and drawing lessons to guide future progress. The program focusses on how astronomy actually progresses, using careful historical studies and real data, rather than anecdotes and folklore.

  15. 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).

  16. 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

  17. 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

  18. Recent Discoveries in Nuclear Line Astrophysics

    NASA Astrophysics Data System (ADS)

    Boggs, Steven E.

    2016-06-01

    Nuclear gamma-ray lines provide a unique probe of supernovae and nuclear astrophysics. The potential for significant contributions to the understanding supernovae, as well as the large potential for new discoveries, has long been recognized. I will review several major discoveries in the past few years from the NuSTAR and INTEGRAL missions, including observations of SN 1987A, Cas A, and SN 2014J. In addition, I will look forward to the next generation of gamma-ray line instruments currently under development, including wide-field Compton telescopes and focusing lens telescopes.

  19. What's new, Voyager: The discoveries continue

    NASA Technical Reports Server (NTRS)

    Miner, Ellis D.

    1995-01-01

    The twin Voyager spacecraft, launched nearly two decades ago, continue to operate and are now searching for the edge of our solar system, the heliopause. Voyager's giant-planet flybys of Jupiter, Saturn, Uranus, and Neptune have provided data that are likely to remain the definitive data set for the foreseeable future and have led to many ongoing discoveries. As the spacecraft move toward the heliopause, they are also providing data on the structure of the heliosphere. This article discusses the discoveries resulting from the flyby and heliosphere data that have been made within the past five years.

  20. 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.

  1. 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. PMID:26791724

  2. Novel approaches to discovery of antibacterial agents.

    PubMed

    Taylor, Patricia L; Wright, Gerard D

    2008-12-01

    Antimicrobial resistance is a rapidly increasing problem impacting the successful treatment of bacterial infectious disease. To combat resistance, the development of new treatment options is required. Recent advances in technology have aided in the discovery of novel antibacterial agents, specifically through genome mining for novel natural product biosynthetic gene clusters and improved small molecule high-throughput screening methods. Novel targets such as lipopolysaccharide and fatty acid biosyntheses have been identified by essential gene studies, representing a shift from traditional antibiotic targets. Finally, inhibiting non-essential genes with small molecules is being explored as a method for rescuing the activity of 'old' antibiotics, providing a novel synergistic approach to antimicrobial discovery.

  3. 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.

  4. 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.

  5. Shell appraising deepwater discovery off Philippines

    SciTech Connect

    Scherer, M. ); Lambers, E.J.T.; Steffens, G.S. )

    1993-05-10

    Shell International Petroleum Co. Ltd. negotiated a farmout in 1990 from Occidental International Exploration and Production Co. for Block SC-38 in the South China Sea off Palawan, Philippines, following Oxy's discovery of gas in 1989 in a Miocene Nido limestone buildup. Under the terms of the farmout agreement, Shell became operator with a 50% share. Following the disappointing well North Iloc 1, Shell was successful in finding oil and gas in Malampaya 1. Water 700-1,000 m deep, remoteness, and adverse weather conditions have imposed major challenges for offshore operations. The paper describes the tectonic setting; the Nido limestone play; the Malampaya discovery; and Shell's appraisal studies.

  6. 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.

  7. Opportunities for isotope discoveries at FRIB

    NASA Astrophysics Data System (ADS)

    Baumann, T.; Hausmann, M.; Sherrill, B. M.; Tarasov, O. B.

    2016-06-01

    Expected production yields of the Facility for Rare Isotope Beams (FRIB) were calculated for a wide range of rare isotopes using the code LISE++ and planned performance parameters (Tarasov and Bazin, 2008; Bollen et al., 2011 [2]). A comparison between isotope discoveries of the last decade and expected particle yields indicates the range of isotopes that can likely be detected at FRIB. This paper will highlight recent isotope discoveries at NSCL's Coupled Cyclotron Facility and deduce how far the limits could be pushed with the Facility for Rare Isotope Beams.

  8. Anammox bacteria: from discovery to application.

    PubMed

    Kuenen, J Gijs

    2008-04-01

    Anaerobic ammonium oxidation (anammox) bacteria, which were discovered in waste-water sludge in the early 1990s, have the unique metabolic ability to combine ammonium and nitrite or nitrate to form nitrogen gas. This discovery led to the realization that a substantial part of the enormous nitrogen losses that are observed in the marine environment--up to 50% of the total nitrogen turnover--were due to the activity of these bacteria. In this Timeline, Gijs Kuenen recalls the discovery of these unique microorganisms and describes the continuing elucidation of their roles in environmental and industrial microbiology.

  9. 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

  10. 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.

  11. Target deconvolution strategies in drug discovery.

    PubMed

    Terstappen, Georg C; Schlüpen, Christina; Raggiaschi, Roberto; Gaviraghi, Giovanni

    2007-11-01

    Recognition of some of the limitations of target-based drug discovery has recently led to the renaissance of a more holistic approach in which complex biological systems are investigated for phenotypic changes upon exposure to small molecules. The subsequent identification of the molecular targets that underlie an observed phenotypic response--termed target deconvolution--is an important aspect of current drug discovery, as knowledge of the molecular targets will greatly aid drug development. Here, the broad panel of experimental strategies that can be applied to target deconvolution is critically reviewed.

  12. Involve physicians in marketing.

    PubMed

    Randolph, G T; Baker, K M; Laubach, C A

    1984-01-01

    Many everyday problems in medical group practice can be attacked by a marketing approach. To be successful, however, this kind of approach must have the full support of those involved, especially the physicians, since they are the principal providers of healthcare services. When marketing is presented in a broad context, including elements such as patient mix, population distribution, and research, physicians are more likely to be interested and supportive. The members of Geisinger Medical Center's Department of Cardiovascular Medicine addressed their patient appointment backlog problem with a marketing approach. Their method is chronicled here and serves as a fine example of how physician involvement in marketing can lead to a positive outcome.

  13. 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.

  14. Discovery of novel drug targets and their functions using phenotypic screening of natural products.

    PubMed

    Chang, Junghwa; Kwon, Ho Jeong

    2016-03-01

    Natural products are valuable resources that provide a variety of bioactive compounds and natural pharmacophores in modern drug discovery. Discovery of biologically active natural products and unraveling their target proteins to understand their mode of action have always been critical hurdles for their development into clinical drugs. For effective discovery and development of bioactive natural products into novel therapeutic drugs, comprehensive screening and identification of target proteins are indispensable. In this review, a systematic approach to understanding the mode of action of natural products isolated using phenotypic screening involving chemical proteomics-based target identification is introduced. This review highlights three natural products recently discovered via phenotypic screening, namely glucopiericidin A, ecumicin, and terpestacin, as representative case studies to revisit the pivotal role of natural products as powerful tools in discovering the novel functions and druggability of targets in biological systems and pathological diseases of interest.

  15. The Maillard reaction in the human body. The main discoveries and factors that affect glycation.

    PubMed

    Tessier, F J

    2010-06-01

    Ever since the discovery of the Maillard reaction in 1912 and the discovery of the interaction between advanced glycation end-products and cellular receptors, impressive progress has been made in the knowledge of nonenzymatic browning of proteins in vivo. This reaction which leads to the accumulation of random damage in extracellular proteins is known to have deleterious effects on biological function, and is associated with aging and complication in chronic diseases. Despite a controlled membrane permeability and a protective regulation of the cells, intracellular proteins are also altered by the Maillard reaction. Two main factors, protein turnover and the concentration of carbonyls, are involved in the rate of formation of the Maillard products. This paper reviews the key milestones of the discovery of the Maillard reaction in vivo, better known as glycation, and the factors which are likely to affect it.

  16. Resource Discovery and Universal Access: Understanding Enablers and Barriers from the User Perspective.

    PubMed

    Beyene, Wondwossen Mulualem

    2016-01-01

    Resource discovery tools are the keys to explore, find, and retrieve resources from multitudes of collections hosted by library and information systems. Modern resource discovery tools provide facet-rich interfaces that provide multiple alternatives to expose resources for their potential users and help them navigate to the resources they need. This paper examines one of those tools from the perspective of universal access, utilizing the experience of users with print disability. It aimed at exploring the way print disabled users use library search tools, the barriers they might face in the process, and what needs to be considered in order to implement discovery tools that incorporate the needs of users with print disability. Interviews that involved user testing were made with selected group of users. The data obtained in the process was analyzed and compared against the existing body of knowledge to forward design recommendations for future endeavors. PMID:27534350

  17. Materials Discovery via CALYPSO Methodology

    NASA Astrophysics Data System (ADS)

    Ma, Yanming

    2014-03-01

    Materials design has been the subject of topical interests in materials and physical sciences for long. Atomistic structures of materials occupy a central and often critical role, when establishing a correspondence between materials performance and their basic compositions. Theoretical prediction of atomistic structures of materials with the only given information of chemical compositions becomes crucially important, but it is extremely difficult as it basically involves in classifying a huge number of energy minima on the lattice energy surface. To tackle the problems, we have developed an efficient CALYPSO (Crystal structural AnLYsis by Particle Swarm Optimization) approach for structure prediction from scratch based on particle swarm optimization algorithm by taking the advantage of swarm intelligence and the spirit of structures smart learning. The method has been coded into CALYPSO software (http://www.calypso.cn) which is free for academic use. Currently, CALYPSO method is able to predict structures of three-dimensional crystals, isolated clusters or molecules, surface reconstructions, and two-dimensional layers. The applications of CALYPSO into purposed materials design of layered materials, high-pressure superconductors, and superhard materials were successfully made. Our design of superhard materials introduced a useful scheme, where the hardness value has been employed as the fitness function. This strategy might also be applicable into design of materials with other desired functional properties (e.g., thermoelectric figure of merit, topological Z2 number, etc.). For such a structural design, a well-understood structure to property formulation is required, by which functional properties of materials can be easily acquired at given structures. An emergent application is seen on design of photocatalyst materials.

  18. HISTORY OF THE ORIGIN OF THE CHEMICAL ELEMENTS AND THEIR DISCOVERIES.

    SciTech Connect

    HOLDEN,N.E.

    2001-06-29

    The origin of the chemical elements show a wide diversity with some of these elements having their origin in antiquity. Still other elements have been synthesized within the past fifty years via nuclear reactions on heavy elements, because these other elements are unstable and radioactive and do not exist in nature. The names of the elements come from many sources including mythological concepts or characters; places, areas or countries; properties of the element or its compounds, such as color, smell or its inability to combine; and the names of scientists. There are also some miscellaneous names as well as some obscure names for particular elements. The claim of discovery of an element has varied over the centuries. Many claims, e.g., the discovery of certain rare earth elements of the lanthanide series, involved the discovery of a mineral ore from which an element was later extracted. The honor of discovery has often been accorded not to the person who first isolated the element but to the person who discovered the original mineral itself, even when the ore was impure and contained many elements. The reason for this is that in the case of these rare earth elements, the ''earth'' now refers to oxides of a metal not to the metal itself. This fact was not realized at the time of their discovery, until the English chemist Humphry Davy showed that earths were compounds of oxygen and metals in 1808. In the early discoveries, the atomic weight of an element and spectral analysis of the element were not available. Later both of these elemental properties would be required before discovery of the element would be accepted. In general, the requirements for discovery claims have tightened through the years and claims that were previously accepted would no longer meet the minimum constraints now imposed. There are cases where the honor of discovery is not given to the first person to actually discover the element but to the first person to claim the discovery in print. If a

  19. Strengthening Parent Involvement.

    ERIC Educational Resources Information Center

    Williams, David L., Jr.; Chavkin, Nancy Feyl

    1986-01-01

    Recent studies have verified Secretary of Education William Bennett's observation on the importance of home and family life. The most successful students are those whose parents become actively engaged in the educational process at home and at school. To capitalize on potential parent involvement, principals need to understand the kinds of…

  20. Parent Involvement. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2007-01-01

    What are some ways in which to get parents meaningfully involved in their child's high school? According to the research, the most successful programs are those that provide a variety of ways in which parents can be actively engaged in their child's academic life. Joyce Epstein, Director of the National Network of Partnership Schools, out of Johns…