Comparing the Consumption of CPU Hours with Scientific Output for the Extreme Science and Engineering Discovery Environment (XSEDE).

PubMed

Knepper, Richard; Börner, Katy

2016-01-01

This paper presents the results of a study that compares resource usage with publication output using data about the consumption of CPU cycles from the Extreme Science and Engineering Discovery Environment (XSEDE) and resulting scientific publications for 2,691 institutions/teams. Specifically, the datasets comprise a total of 5,374,032,696 central processing unit (CPU) hours run in XSEDE during July 1, 2011 to August 18, 2015 and 2,882 publications that cite the XSEDE resource. Three types of studies were conducted: a geospatial analysis of XSEDE providers and consumers, co-authorship network analysis of XSEDE publications, and bi-modal network analysis of how XSEDE resources are used by different research fields. Resulting visualizations show that a diverse set of consumers make use of XSEDE resources, that users of XSEDE publish together frequently, and that the users of XSEDE with the highest resource usage tend to be "traditional" high-performance computing (HPC) community members from astronomy, atmospheric science, physics, chemistry, and biology.

Comparing the Consumption of CPU Hours with Scientific Output for the Extreme Science and Engineering Discovery Environment (XSEDE)

PubMed Central

Börner, Katy

2016-01-01

This paper presents the results of a study that compares resource usage with publication output using data about the consumption of CPU cycles from the Extreme Science and Engineering Discovery Environment (XSEDE) and resulting scientific publications for 2,691 institutions/teams. Specifically, the datasets comprise a total of 5,374,032,696 central processing unit (CPU) hours run in XSEDE during July 1, 2011 to August 18, 2015 and 2,882 publications that cite the XSEDE resource. Three types of studies were conducted: a geospatial analysis of XSEDE providers and consumers, co-authorship network analysis of XSEDE publications, and bi-modal network analysis of how XSEDE resources are used by different research fields. Resulting visualizations show that a diverse set of consumers make use of XSEDE resources, that users of XSEDE publish together frequently, and that the users of XSEDE with the highest resource usage tend to be “traditional” high-performance computing (HPC) community members from astronomy, atmospheric science, physics, chemistry, and biology. PMID:27310174

Importance of microbial natural products and the need to revitalize their discovery.

PubMed

Demain, Arnold L

2014-02-01

Microbes are the leading producers of useful natural products. Natural products from microbes and plants make excellent drugs. Significant portions of the microbial genomes are devoted to production of these useful secondary metabolites. A single microbe can make a number of secondary metabolites, as high as 50 compounds. The most useful products include antibiotics, anticancer agents, immunosuppressants, but products for many other applications, e.g., antivirals, anthelmintics, enzyme inhibitors, nutraceuticals, polymers, surfactants, bioherbicides, and vaccines have been commercialized. Unfortunately, due to the decrease in natural product discovery efforts, drug discovery has decreased in the past 20 years. The reasons include excessive costs for clinical trials, too short a window before the products become generics, difficulty in discovery of antibiotics against resistant organisms, and short treatment times by patients for products such as antibiotics. Despite these difficulties, technology to discover new drugs has advanced, e.g., combinatorial chemistry of natural product scaffolds, discoveries in biodiversity, genome mining, and systems biology. Of great help would be government extension of the time before products become generic.

An overview of aldehyde oxidase: an enzyme of emerging importance in novel drug discovery.

PubMed

Rashidi, Mohammad-Reza; Soltani, Somaieh

2017-03-01

Given the rising trend in medicinal chemistry strategy to reduce cytochrome P450-dependent metabolism, aldehyde oxidase (AOX) has recently gained increased attention in drug discovery programs and the number of drug candidates that are metabolized by AOX is steadily growing. Areas covered: Despite the emerging importance of AOX in drug discovery, there are certain major recognized problems associated with AOX-mediated metabolism of drugs. Intra- and inter-species variations in AOX activity, the lack of reliable and predictive animal models using the common experimental animals, and failure in the predictions of in vivo metabolic activity of AOX using traditional in vitro methods are among these issues that are covered in this article. A comprehensive review of computational human AOX (hAOX) related studies are also provided. Expert opinion: Following the recent progress in the stem cell field, the authors recommend the application of organoids technology as an effective tool to solve the fundamental problems associated with the evaluation of AOX in drug discovery. The recent success in resolving the hAOX crystal structure can too be another valuable data source for the study of AOX-catalyzed metabolism of new drug candidates, using computer-aided drug discovery methods.

Use of the CO I Gene as a Species Indicator for Forensically Important Flies: A Forensic Entomology Laboratory Exercise

ERIC Educational Resources Information Center

Honda, Jeffrey Y.

2008-01-01

Forensic entomologists utilize insects (particularly flies) to establish the time interval between death and body discovery. This important piece of information may answer questions as to the circumstances of the individual's death and insects are now routinely utilized and recognized as being important forensic indicators. Of extreme importance…

The importance of extreme weight percentile in postoperative morbidity in children.

PubMed

Stey, Anne M; Moss, R Lawrence; Kraemer, Kari; Cohen, Mark E; Ko, Clifford Y; Lee Hall, Bruce

2014-05-01

Anthropometric data are important indicators of child health. This study sought to determine whether anthropometric data of extreme weight were significant predictors of perioperative morbidity in pediatric surgery. This was a cohort study of children 29 days up to 18 years of age undergoing surgical procedures at participating American College of Surgeons' NSQIP Pediatric hospitals in 2011 and 2012. The primary outcomes were composite morbidity and surgical site infection. The primary predictor of interest was weight percentile, which was divided into the following categories: ≤5(th) percentile, 6(th) to 94(th), or ≥95(th) percentile. A hierarchical multivariate logistic model, adjusting for procedure case mix, demographic, and clinical patient characteristic variables, was used to quantify the relationship between weight percentile category and outcomes. Children in the ≤5th weight percentile had 1.19-fold higher odds of overall postoperative morbidity developing than children in the nonextreme range (95% CI, 1.10-1.30) when controlling for clinical variables. Yet these children did not have higher odds of surgical site infection developing. Children in the ≥95(th) weight percentile did not have a significant increase in overall postoperative morbidity. However, they were at 1.35-fold increased odds of surgical site infection compared with those in the nonextreme range when controlling for clinical variables (95% CI, 1.16-1.57). Both extremely high and extremely low weight percentile scores can be associated with increased postoperative complications after controlling for clinical variables. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Discovery of extra-terrestrial life: assessment by scales of its importance and associated risks.

PubMed

Almár, Iván; Race, Margaret S

2011-02-13

The Rio Scale accepted by the SETI Committee of the International Academy of Astronautics in 2002 is intended for use in evaluating the impact on society of any announcement regarding the discovery of evidence of extra-terrestrial (ET) intelligence. The Rio Scale is mathematically defined using three parameters (class of phenomenon, type of discovery and distance) and a δ factor, the assumed credibility of a claim. This paper proposes a new scale applicable to announcements alleging evidence of ET life within or outside our Solar System. The London Scale for astrobiology has mathematical structure and logic similar to the Rio Scale, and uses four parameters (life form, nature of phenomenon, type of discovery and distance) as well as a credibility factor δ to calculate a London Scale index (LSI) with values ranging from 0 to 10. The level of risk or biohazard associated with a purported discovery is evaluated independently of the LSI value and may be ranked in four categories. The combined information is intended to provide a scalar assessment of the scientific importance, validity and potential risks associated with putative evidence of ET life discovered on Earth, on nearby bodies in the Solar System or in our Galaxy.

Estimating the Effect of Climate Change on Crop Yields and Farmland Values: The Importance of Extreme Temperatures

EPA Pesticide Factsheets

This is a presentation titled Estimating the Effect of Climate Change on Crop Yields and Farmland Values: The Importance of Extreme Temperatures that was given for the National Center for Environmental Economics

A discovery! The Higgs? Why is this important? How it was done.

ScienceCinema

Dawson, Sally; Gordan, Howard

2017-12-09

Data collected during 2011 and 2012 at the Large Hadron Collider (LHC) at CERN in Switzerland, the world's highest-energy proton collider, has culminated in the discovery of a new particle that is about 135 times heavier than a proton. But is it really the Higgs particle predicted by the theory that explains the origin of the mass of most elementary particles in the universe? The discovery and its possible identity is discussed by two Brookhaven Lab physicists, Sally Dawson and Howard Gordon, with deep roots in the hunt for the Higgs.

The importance of Leonhard Euler's discoveries in the field of shipbuilding for the scientific evolution of academician A. N. Krylov

NASA Astrophysics Data System (ADS)

Sharkov, N. A.; Sharkova, O. A.

2018-05-01

The paper identifies the importance of the Leonhard Euler's discoveries in the field of shipbuilding for the scientific evolution of academician A. N. Krylov and for the modern knowledge in survivability and safety of ships. The works by Leonard Euler "Marine Science" and "The Moon Motion New Theory" are discussed.

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…

An important Norwegian contribution to the study of the bursae of the upper and lower extremities.

PubMed

Musil, Vladimir; Selnes, Christoffer V; Falck, Aleksander T; Sandve, Lars; Shekarchi, Siamek; O'Donnell, Bruce; Kachlik, David

2010-10-01

We present a critical analysis of the monograph of A.S.D. Synnestvedt (1869) “En anatomisk beskrivelse af de paa over- og underestremiteterne forekommende Bursae mucosae”. The analysis was completed using anatomical information from the historically oldest publications dealing with the bursae of the extremities: Albinus (1734) , Monro (1788) , Rosenmüller (1799) . We are of the opinion that Synnestvedt's publication is important, not only historically but also as a source of information for recent medical practitioners. Synnestvedt's monograph has a wealth of literary citations, unambiguous opinions of seasoned anatomists regarding the structure and function of the synovial membrane, and detailed descriptions of dissections he performed on fetal and adult cadavers. The information in this publication may enhance the diagnosis of bursopathies and enthesopathies of the extremities.

An important Norwegian contribution to the study of the bursae of the upper and lower extremities

PubMed Central

2010-01-01

We present a critical analysis of the monograph of A.S.D. Synnestvedt (1869) “En anatomisk beskrivelse af de paa over- og underestremiteterne forekommende Bursae mucosae”. The analysis was completed using anatomical information from the historically oldest publications dealing with the bursae of the extremities: Albinus (1734), Monro (1788), Rosenmüller (1799). We are of the opinion that Synnestvedt's publication is important, not only historically but also as a source of information for recent medical practitioners. Synnestvedt's monograph has a wealth of literary citations, unambiguous opinions of seasoned anatomists regarding the structure and function of the synovial membrane, and detailed descriptions of dissections he performed on fetal and adult cadavers. The information in this publication may enhance the diagnosis of bursopathies and enthesopathies of the extremities. PMID:20860444

Serendipity: Accidental discoveries in science. [A description of important scientific facts discovered by accident

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

Roberts, R.M.

1989-01-01

In contrast to a few pseudoserendipitous discoveries are the truly serendipitous discoveries: fortuitous accidents that led to new things totally unexpected and unsought for. Any of these accidents could have gone unnoticed and would have thus remained simply an accident of no importance. Instead, because of the sagacity of the individuals who encountered the accidents, we have an explanation of the laws that govern the movement of the planets; the founding of the science of organic chemistry on a rational basis; the beginning of understanding the relationship of molecular structure to physiological activity; beautiful dyes that anyone, not just royalty,more » can afford; insight into the culture and language of ancient civilizations; x rays for medical diagnosis and treatment; radioactivity and nuclear energy; vaccination against smallpox and other diseases; the miracle drug'' penicillin and its successors; nylon and polyester for clothing; Teflon for frying pans and heart valves; other polymers for plastic garbage bags, ice chests, radar insulation, water-ski ropes, bullet-proof shields, and airplane windows; and synthetic molecules that promise to mimic the vital actions of nature's enzymes. These are just a few of the benefits of serendipity, discoveries made by accident and sagacity of things which they (certain gifted individuals) were not actually in quest of. ''« less

Flood AI: An Intelligent Systems for Discovery and Communication of Disaster Knowledge

NASA Astrophysics Data System (ADS)

Demir, I.; Sermet, M. Y.

2017-12-01

Communities are not immune from extreme events or natural disasters that can lead to large-scale consequences for the nation and public. Improving resilience to better prepare, plan, recover, and adapt to disasters is critical to reduce the impacts of extreme events. The National Research Council (NRC) report discusses the topic of how to increase resilience to extreme events through a vision of resilient nation in the year 2030. The report highlights the importance of data, information, gaps and knowledge challenges that needs to be addressed, and suggests every individual to access the risk and vulnerability information to make their communities more resilient. This project presents an intelligent system, Flood AI, for flooding to improve societal preparedness by providing a knowledge engine using voice recognition, artificial intelligence, and natural language processing based on a generalized ontology for disasters with a primary focus on flooding. The knowledge engine utilizes the flood ontology and concepts to connect user input to relevant knowledge discovery channels on flooding by developing a data acquisition and processing framework utilizing environmental observations, forecast models, and knowledge bases. Communication channels of the framework includes web-based systems, agent-based chat bots, smartphone applications, automated web workflows, and smart home devices, opening the knowledge discovery for flooding to many unique use cases.

The Coldest Discoveries of Backyard Worlds

NASA Astrophysics Data System (ADS)

Faherty, Jacqueline; Kuchner, Marc; Logsdon, Sarah; Bardalez Gagliuffi, Daniella; Meisner, Aaron; Schneider, Adam; Gagne, Jonathan; Caselden, Dan

2018-05-01

Over the past five years, our view of the local solar neighborhood has changed drastically thanks to the Wide Field Infrared Survey Explorer (WISE). Not only did WISE redefine the five closest systems to the Sun with the discovery of Luhman16AB and WISE0855, but it also revealed the Sun's closest fly by and it defined an entirely new class of extremely cold and close compact objects: the Y dwarfs. At present, all but two of the Y dwarfs were discovered through a WISE single epoch photometric identification. As a whole, these objects are of critical importance to identifying the efficiency of star formation at the lowest masses. As individuals, each of these objects represents a unique probe into the complex chemistry present in the coldest photospheres produced in the Universe. Every single Y dwarf discovered is an observational treasure. In February 2017, we launched a citizen science project called Backyard Worlds: Planet 9 with the intention of scanning the entire sky using not just photometric information but positional as well to identify the coldest, closest, and fastest moving objects near the Sun. In this Spitzer Cycle 14 proposal, we have identified 65 tantalizingly fast moving objects that appear to be extremely cold hence potentially among the Sun's nearest neighbors. We ask for 26.8 hours with Spitzer to obtain critical ch1 and ch2 photometry as well as astrometric information (to confirm motion) which will allow us to characterize these new cold brown dwarf neighbors. The coldest objects discovered through this proposal will be important follow-up targets for JWST spectroscopy.

[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.

The Importance of Studying Past Extreme Floods to Prepare for Uncertain Future Extremes

NASA Astrophysics Data System (ADS)

Burges, S. J.

2016-12-01

Hoyt and Langbein, 1955 in their book `Floods' wrote: " ..meteorologic and hydrologic conditions will combine to produce superfloods of unprecedented magnitude. We have every reason to believe that in most rivers past floods may not be an accurate measure of ultimate flood potentialities. It is this superflood with which we are always most concerned". I provide several examples to offer some historical perspective on assessing extreme floods. In one example, flooding in the Miami Valley, OH in 1913 claimed 350 lives. The engineering and socio-economic challenges facing the Morgan Engineering Co in how to mitigate against future flood damage and loss of life when limited information was available provide guidance about ways to face an uncertain hydroclimate future, particularly one of a changed climate. A second example forces us to examine mixed flood populations and illustrates the huge uncertainty in assigning flood magnitude and exceedance probability to extreme floods in such cases. There is large uncertainty in flood frequency estimates; knowledge of the total flood hydrograph, not the peak flood flow rate alone, is what is needed for hazard mitigation assessment or design. Some challenges in estimating the complete flood hydrograph in an uncertain future climate, including demands on hydrologic models and their inputs, are addressed.

Phase transformation in tantalum under extreme laser deformation

DOE PAGES

Lu, C. -H.; Hahn, E. N.; Remington, B. A.; ...

2015-10-19

The structural and mechanical response of metals is intimately connected to phase transformations. For instance, the product of a phase transformation (martensite) is responsible for the extraordinary range of strength and toughness of steel, making it a versatile and important structural material. Although abundant in metals and alloys, the discovery of new phase transformations is not currently a common event and often requires a mix of experimentation, predictive computations, and luck. High-energy pulsed lasers enable the exploration of extreme pressures and temperatures, where such discoveries may lie. The formation of a hexagonal (omega) phase was observed in recovered monocrystalline body-centeredmore » cubic tantalum of four crystallographic orientations subjected to an extreme regime of pressure, temperature, and strain-rate. This was accomplished using high-energy pulsed lasers. The omega phase and twinning were identified by transmission electron microscopy at 70 GPa (determined by a corresponding VISAR experiment). It is proposed that the shear stresses generated by the uniaxial strain state of shock compression play an essential role in the transformation. In conclusion, molecular dynamics simulations show the transformation of small nodules from body-centered cubic to a hexagonal close-packed structure under the same stress state (pressure and shear).« less

Phase Transformation in Tantalum under Extreme Laser Deformation

PubMed Central

Lu, C.-H.; Hahn, E. N.; Remington, B. A.; Maddox, B. R.; Bringa, E. M.; Meyers, M. A.

2015-01-01

The structural and mechanical response of metals is intimately connected to phase transformations. For instance, the product of a phase transformation (martensite) is responsible for the extraordinary range of strength and toughness of steel, making it a versatile and important structural material. Although abundant in metals and alloys, the discovery of new phase transformations is not currently a common event and often requires a mix of experimentation, predictive computations, and luck. High-energy pulsed lasers enable the exploration of extreme pressures and temperatures, where such discoveries may lie. The formation of a hexagonal (omega) phase was observed in recovered monocrystalline body-centered cubic tantalum of four crystallographic orientations subjected to an extreme regime of pressure, temperature, and strain-rate. This was accomplished using high-energy pulsed lasers. The omega phase and twinning were identified by transmission electron microscopy at 70 GPa (determined by a corresponding VISAR experiment). It is proposed that the shear stresses generated by the uniaxial strain state of shock compression play an essential role in the transformation. Molecular dynamics simulations show the transformation of small nodules from body-centered cubic to a hexagonal close-packed structure under the same stress state (pressure and shear). PMID:26478106

SemaTyP: a knowledge graph based literature mining method for drug discovery.

PubMed

Sang, Shengtian; Yang, Zhihao; Wang, Lei; Liu, Xiaoxia; Lin, Hongfei; Wang, Jian

2018-05-30

Drug discovery is the process through which potential new medicines are identified. High-throughput screening and computer-aided drug discovery/design are the two main drug discovery methods for now, which have successfully discovered a series of drugs. However, development of new drugs is still an extremely time-consuming and expensive process. Biomedical literature contains important clues for the identification of potential treatments. It could support experts in biomedicine on their way towards new discoveries. Here, we propose a biomedical knowledge graph-based drug discovery method called SemaTyP, which discovers candidate drugs for diseases by mining published biomedical literature. We first construct a biomedical knowledge graph with the relations extracted from biomedical abstracts, then a logistic regression model is trained by learning the semantic types of paths of known drug therapies' existing in the biomedical knowledge graph, finally the learned model is used to discover drug therapies for new diseases. The experimental results show that our method could not only effectively discover new drug therapies for new diseases, but also could provide the potential mechanism of action of the candidate drugs. In this paper we propose a novel knowledge graph based literature mining method for drug discovery. It could be a supplementary method for current drug discovery methods.

Extreme optical Fe II emission in luminous IRAS active galactic nuclei

NASA Technical Reports Server (NTRS)

Lipari, Sebastian; Terlevich, Roberto; Macchetto, F.

1993-01-01

Results of a program of studies and observations of strong optical Fe II emission in luminous and ultraluminous IRAS AGN are presented. New spectroscopic observations and studies of three known ultraluminous IRAS AGN with extreme optical Fe II emission, the discovery that PHL 1092 is a new ultraluminous IRAS AGN, and the detection of two new AGN with strongly variable flux in the optical Fe II emission lines are reported. These results are used to test the correlations between the Fe II emission and properties at other wavelengths such as the L(IR) and the radio emission. IR AGN with extreme Fe II emission are found to belong to a very important group of AGN, whose properties provide insight into the origin of the extreme Fe II emission and into the relation between the starburst and AGN phenomena.

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.

Comprehensive Clinical Phenotyping and Genetic Mapping for the Discovery of Autism Susceptibility Genes

DTIC Science & Technology

2013-03-14

SUPPLEMENTARY NOTES 14. ABSTRACT Autism is an extremely common and heterogeneous neurodevelopmental disorder. While genetic factors are known to play...AFRL-SA-WP-TR-2013-0013 Comprehensive Clinical Phenotyping and Genetic Mapping for the Discovery of Autism Susceptibility Genes...Genetic Mapping for the Discovery of Autism Susceptibility Genes 5a. CONTRACT NUMBER N/A 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT NUMBER N/A 6

Computational drug discovery

PubMed Central

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

2012-01-01

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

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.

Discovery touches down after successful mission STS-95

NASA Technical Reports Server (NTRS)

1998-01-01

Orbiter Discovery smokes its tires as it touches down on runway 33 at the Shuttle Landing Facility. Discovery returns to Earth with its crew of seven after a successful mission STS-95 lasting nearly nine days and 3.6 million miles. The mission included research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

The Discovery of Archaea, the 'Third Branch of Life', and Its Impacts

Science.gov Websites

dropdown arrow Site Map A-Z Index Menu Synopsis The Discovery of Archaea, the 'Third Branch of Life', and different. For example, archaea can thrive in extreme conditions that would kill other life forms. In the Environmental Research in the Atomic Age 2 Edited excerpt from Verifying the "Third Branch of Life"

The Europa Ocean Discovery mission

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

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`smore » 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.« less

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.

Communicating Our Science to Our Customers: Drug Discovery in Five Simple Experiments.

PubMed

Pearson, Lesley-Anne; Foley, David William

2017-02-09

The complexities of modern drug discovery-an interdisciplinary process that often takes years and costs billions-can be extremely challenging to explain to a public audience. We present details of a 30 minute demonstrative lecture that uses well-known experiments to illustrate key concepts in drug discovery including synthesis, assay and metabolism.

Discovery touches down after successful mission STS-95

NASA Technical Reports Server (NTRS)

1998-01-01

Orbiter Discovery startles a great white egret next to runway 33 as it touches down at the Shuttle Landing Facility. Discovery returns to Earth with its crew of seven after a successful mission STS-95 lasting nearly nine days and 3.6 million miles. The mission included research payloads such as the Spartan solar- observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

The relation between prior knowledge and students' collaborative discovery learning processes

NASA Astrophysics Data System (ADS)

Gijlers, Hannie; de Jong, Ton

2005-03-01

In this study we investigate how prior knowledge influences knowledge development during collaborative discovery learning. Fifteen dyads of students (pre-university education, 15-16 years old) worked on a discovery learning task in the physics field of kinematics. The (face-to-face) communication between students was recorded and the interaction with the environment was logged. Based on students' individual judgments of the truth-value and testability of a series of domain-specific propositions, a detailed description of the knowledge configuration for each dyad was created before they entered the learning environment. Qualitative analyses of two dialogues illustrated that prior knowledge influences the discovery learning processes, and knowledge development in a pair of students. Assessments of student and dyad definitional (domain-specific) knowledge, generic (mathematical and graph) knowledge, and generic (discovery) skills were related to the students' dialogue in different discovery learning processes. Results show that a high level of definitional prior knowledge is positively related to the proportion of communication regarding the interpretation of results. Heterogeneity with respect to generic prior knowledge was positively related to the number of utterances made in the discovery process categories hypotheses generation and experimentation. Results of the qualitative analyses indicated that collaboration between extremely heterogeneous dyads is difficult when the high achiever is not willing to scaffold information and work in the low achiever's zone of proximal development.

Overview of the Coastal Marine Discovery Service: data discovery, visualization, and understanding

NASA Astrophysics Data System (ADS)

Armstrong, E. M.; Mattmann, C. A.; Cinquini, L.; O'Brien, F. J.; Resneck, G.; Siegrist, Z.

2012-12-01

Many resources available for coastal ocean research and management remain underutilized. Typically, the emphasis in the past has been on increasing access and usability of remote sensing satellite products from NASA data centers. Significant progress has been made in this regard although access and discovery mechanisms still remain disjointed. Less attention has been paid to discovery and usability to ocean in situ records and circulation model products, because typically these are organized and maintained on a smaller regional level such as a university or smaller division of a larger national agency. The NASA Coastal Marine Discovery Service, a NASA ACCESS funded activity, focuses on improving discovery of these regional coastal ocean web services and data portals, including databases for satellite imagery, in situ and field measurements, ocean circulation models, and GIS coverages as a few examples. Beyond resource discovery, the CMDS integrated system (http://cmds.jpl.nasa.gov) leverages open source technology for unifying coastal ocean data within the framework on a GIS web client, the Easy GIS Net Viewer. In sum, CMDS consists of an online catalog of coastal resources that allows users to quickly discover the availability of data for their region of interest, physical parameter of interest or specific regional project of interest, or any combination of these. After discovery, data can be transparently linked to Netviewer client to view, overlay and interrogate products, and make GIS-like queries on the data layers to investigate statistical relationships. In this presentation, we will review the CMDS system, it architecture and resource harvesting approach, and more importantly demonstrate real world use of cases of data exploration, visualization and ultimately understanding.

On the importance of cloud—cloud interaction to invigorate convective extremes

NASA Astrophysics Data System (ADS)

Berg, Peter; Moseley, Christopher; Hohenegger, Cathy; Haerter, Jan

2017-04-01

Observational studies have shown that convective extremes are invigorated with increasing temperatures beyond thermodynamic constraints through the Clausius-Clapeyron relationship (e.g. Lenderink and van Meijgaard, Nature Geosci., 2008; Berg et al., Nature Geosci., 2013). This implies that there are changes in the dynamics of the convective showers that are dependent on the environmental conditions. Observations of convective cells lack sufficient resolution to investigate the dynamics in detail. We have therefore applied a large eddy simulator (LES) at a 200 m horizontal resolution to study the dynamical interaction between convective cells in a set of idealized simulations of a full diurnal cycle with a vertical profile of a typical day with convective showers (Moseley et al., Nature Geosci., 2016). The simulations show that the convective cells are subjected to a gradual self-organization over the day, forming larger cell clusters and more intense precipitation. Further, by tracking rain cells, we find that cells that collide with other cells during their lifetime have a different response to changes in the environmental conditions, such as an increase in temperature, than cells that do not interact. Whereas the non-interacting cells remain almost unaffected by the boundary conditions, the colliding cells show a strong invigoration. Interestingly, granting more time for the self-organization to occur has a similar effect as increasing the temperature. We therefore speculate that self-organization is a key element to explain the strong response of convective extremes to increasing temperature. Our results suggest that proper modeling and predicting of convective extremes requires the description of the interaction between convective clouds.

Quantitative trait Loci analysis using the false discovery rate.

PubMed

Benjamini, Yoav; Yekutieli, Daniel

2005-10-01

False discovery rate control has become an essential tool in any study that has a very large multiplicity problem. False discovery rate-controlling procedures have also been found to be very effective in QTL analysis, ensuring reproducible results with few falsely discovered linkages and offering increased power to discover QTL, although their acceptance has been slower than in microarray analysis, for example. The reason is partly because the methodological aspects of applying the false discovery rate to QTL mapping are not well developed. Our aim in this work is to lay a solid foundation for the use of the false discovery rate in QTL mapping. We review the false discovery rate criterion, the appropriate interpretation of the FDR, and alternative formulations of the FDR that appeared in the statistical and genetics literature. We discuss important features of the FDR approach, some stemming from new developments in FDR theory and methodology, which deem it especially useful in linkage analysis. We review false discovery rate-controlling procedures--the BH, the resampling procedure, and the adaptive two-stage procedure-and discuss the validity of these procedures in single- and multiple-trait QTL mapping. Finally we argue that the control of the false discovery rate has an important role in suggesting, indicating the significance of, and confirming QTL and present guidelines for its use.

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.

The Discovery of a Class of High-Temperature Superconductors.

ERIC Educational Resources Information Center

Muller, K. Alex; Bednorz, J. Georg

1987-01-01

Describes the new class of oxide superconductors, the importance of these materials, and the concepts that led to its discovery. Summarizes the discovery itself and its early confirmation. Discusses the observation of a superconductive glass state in percolative samples. (TW)

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)

Commentary: The Hash House Harriers and the winding path to materials discovery

DOE PAGES

Canfield, Paul C.

2015-04-07

Materials science research can be both very demanding and extremely rewarding. In this Commentary, in my own research of new electronic and magnetic materials, I give numerous exemplars of the path followed to materials discovery. I also highlight the parallels between my research experiences with the pastime of running. I hope that my thoughts will help guide junior researchers along the often tortuous and exciting path to new materials and that I can teach them to be open minded and persistent about following new lines of discovery. “No-pain, no-gain” applies to many things in life, running and scientific research beingmore » just two examples, but I hope in the case of scientific research that I can convince you the gain normally outweighs the pain.« less

STS-133 Discovery

NASA Image and Video Library

2010-11-03

The space shuttle Discovery is seen on launch Pad 39a after the Rotating Service Structure (RSS) is rolled back on Wednesday, Nov. 3, 2010 at the NASA Kennedy Space Center in Cape Canaveral, Fla. During space shuttle Discovery's final spaceflight, the STS-133 crew members will take important spare parts to the International Space Station along with the Express Logistics Carrier-4. Photo Credit: (NASA/Bill Ingalls)

10 CFR 590.305 - Informal discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Informal discovery. 590.305 Section 590.305 Energy... WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Procedures § 590.305 Informal discovery. The parties to a proceeding may conduct discovery through use of procedures such as written interrogatories or...

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... WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Procedures § 590.305 Informal discovery. The parties to a proceeding may conduct discovery through use of procedures such as written interrogatories or...

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

Space Shuttle Discovery lifts off successfully

NASA Technical Reports Server (NTRS)

1998-01-01

As if sprung from the rolling exhaust clouds below, Space Shuttle Discovery shoots into the heavens over the blue Atlantic Ocean from Launch Pad 39B on mission STS-95. Lifting off at 2:19 p.m. EST, Discovery carries a crew of six, including Payload Specialist John H. Glenn Jr., senator from Ohio, who is making his second voyage into space after 36 years. Other crew members are Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Payload Specialist Chiaki Mukai, (M.D., Ph.D.), with the National Space Development Agency of Japan (NASDA), Mission Specialist Stephen K. Robinson, Mission Specialist Pedro Duque of Spain, representing the European Space Agency (ESA), and Mission Specialist Scott E. Parazynski. The STS-95 mission includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process. Discovery is expected to return to KSC at 11:49 a.m. EST on Nov. 7.

The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification

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

Wang, Hui; Shi, Tujin; Qian, Wei-Jun

2015-12-04

Mass spectrometry-based proteomics has become an indispensable tool in biomedical research with broad applications ranging from fundamental biology, systems biology, and biomarker discovery. Recent advances in LC-MS have made it become a major technology in clinical applications, especially in cancer biomarker discovery and verification. To overcome the challenges associated with the analysis of clinical samples, such as extremely wide dynamic range of protein concentrations in biofluids and the need to perform high throughput and accurate quantification, significant efforts have been devoted to improve the overall performance of LC-MS bases clinical proteomics. In this review, we summarize the recent advances inmore » LC-MS in the aspect of cancer biomarker discovery and quantification, and discuss its potentials, limitations, and future perspectives.« less

Identifying the donor star of the most extreme ULX pulsar

NASA Astrophysics Data System (ADS)

Heida, Marianne

2017-08-01

Ultraluminous X-ray sources (ULXs) were once among the most promising candidates for long sought after intermediate-mass black holes, owing to their high X-ray luminosities (>10^39 erg/s) and off-nuclear positions. NGC 5907 ULX-1 was a prime example, and since it regularly reaches 10^41 erg/s it was thought to harbour a black hole with a mass of at least 500 solar masses. But in an astonishing discovery, the source was found to exhibit pulsations in the X-rays on second-timescales, revealing it to be a pulsar powered by accretion onto a neutron star with only 1.4 solar masses. This discovery challenges every known theory of accretion onto a compact object, which in this object exceeds the Eddington limit by a factor of 500. It requires us to imagine extreme departures from known accretion theory and/or binary evolution scenarios. The fuel source should be a massive companion star in order to sustain the required mass accretion rate, however X-ray timing favors a low-mass star. With the ability to detect a massive star, a short HST/WFC3 NIR observation would solve this mystery. A detection of a supergiant donor would open the path to future dynamical mass measurements with JWST, while a non-detection would prove that this extreme ULX pulsar contains a low-mass donor star, forcing us to consider new evolutionary formation channels.

STS-133 Discovery

NASA Image and Video Library

2010-11-03

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

Discovery on Pad 39a

NASA Image and Video Library

2010-10-31

The space shuttle Discovery is seen on launch pad 39a early in the morning of Sunday, Oct. 31, 2010 at the NASA Kennedy Space Center in Cape Canaveral, Fla. During Space Shuttle Discovery's final spaceflight, the STS-133 crew members will take important spare parts to the International Space Station along with the Express Logistics Carrier-4. Discovery is targeted for launch at 3:52 p.m. Wednesday, Nov. 3, 2010. Photo Credit: (NASA/Bill Ingalls)

The National Extreme Events Data and Research Center (NEED)

NASA Astrophysics Data System (ADS)

Gulledge, J.; Kaiser, D. P.; Wilbanks, T. J.; Boden, T.; Devarakonda, R.

2014-12-01

The Climate Change Science Institute at Oak Ridge National Laboratory (ORNL) is establishing the National Extreme Events Data and Research Center (NEED), with the goal of transforming how the United States studies and prepares for extreme weather events in the context of a changing climate. NEED will encourage the myriad, distributed extreme events research communities to move toward the adoption of common practices and will develop a new database compiling global historical data on weather- and climate-related extreme events (e.g., heat waves, droughts, hurricanes, etc.) and related information about impacts, costs, recovery, and available research. Currently, extreme event information is not easy to access and is largely incompatible and inconsistent across web sites. NEED's database development will take into account differences in time frames, spatial scales, treatments of uncertainty, and other parameters and variables, and leverage informatics tools developed at ORNL (i.e., the Metadata Editor [1] and Mercury [2]) to generate standardized, robust documentation for each database along with a web-searchable catalog. In addition, NEED will facilitate convergence on commonly accepted definitions and standards for extreme events data and will enable integrated analyses of coupled threats, such as hurricanes/sea-level rise/flooding and droughts/wildfires. Our goal and vision is that NEED will become the premiere integrated resource for the general study of extreme events. References: [1] Devarakonda, Ranjeet, et al. "OME: Tool for generating and managing metadata to handle BigData." Big Data (Big Data), 2014 IEEE International Conference on. IEEE, 2014. [2] Devarakonda, Ranjeet, et al. "Mercury: reusable metadata management, data discovery and access system." Earth Science Informatics 3.1-2 (2010): 87-94.

Forty years of secondhand smoke research: the gap between discovery and delivery.

PubMed

Harris, Jenine K; Luke, Douglas A; Zuckerman, Rachael B; Shelton, Sarah C

2009-06-01

Public health initiatives often focus on the discovery of risk factors associated with disease and death. Although this is an important step in protecting public health, recently the field has recognized that it is critical to move along the continuum from discovery of risk factors to delivery of interventions, and to improve the quality and speed of translating scientific discoveries into practice. To understand how public health problems move from discovery to delivery, citation network analysis was used to examine 1877 articles on secondhand smoke (SHS) published between 1965 and 2005. Data were collected and analyzed in 2006-2007. Citation patterns showed discovery and delivery to be distinct areas of SHS research. There was little cross-citation between discovery and delivery research, including only nine citation connections between the main paths. A discovery article was 83.5% less likely to cite a delivery article than to cite another discovery article (OR=0.165 [95% CI=0.139, 0.197]), and a delivery article was 64.3% less likely (OR=0.357 [95% CI=0.330, 0.386]) to cite a discovery article than to cite another delivery article. Research summaries, such as Surgeon General reports, were cited frequently and appear to bridge the discovery-delivery gap. There was a lack of cross-citation between discovery and delivery, even though they share the goal of understanding and reducing the impact of SHS. Reliance on research summaries, although they provide an important bridge between discovery and delivery, may slow the development of a field.

1974: the discovery of the first binary pulsar

NASA Astrophysics Data System (ADS)

Damour, Thibault

2015-06-01

The 1974 discovery, by Russell A Hulse and Joseph H Taylor, of the first binary pulsar, PSR B1913+16, opened up new possibilities for the study of relativistic gravity. PSR B1913+16, as well as several other binary pulsars, provided direct observational proof that gravity propagates at the velocity of light and has a quadrupolar structure. Binary pulsars also provided accurate tests of the strong-field regime of relativistic gravity. General relativity has passed all of the binary pulsar tests with flying colors. The discovery of binary pulsars also had very important consequences for astrophysics, leading to accurate measurement of neutron star masses, improved understanding of the possible evolution scenarios for the co-evolution of binary stars, and proof of the existence of binary neutron stars emitting gravitational waves for hundreds of millions of years, before coalescing in catastrophic events radiating intense gravitational wave signals, and probably also leading to important emissions of electromagnetic radiation and neutrinos. This article reviews the history of the discovery of the first binary pulsar, and describes both its immediate impact and its longer-term effect on theoretical and experimental studies of relativistic gravity.

Magnetars: Challenging the Extremes of Nature

NASA Technical Reports Server (NTRS)

Kouveliotou, Chryssa

2011-01-01

Magnetars are magnetically powered rotating neutron stars with extreme magnetic fields (over 10(exp 14) Gauss). They are discovered and emit predominantly in the X- and gamma-rays. Very few sources (roughly 15) have been found since their discovery in 1987. NASA s Fermi Observatory was launched June 11, 2009; the Fermi Gamma Ray Burst Monitor (GBM) began normal operations on July 14, about a month after launch, when the trigger algorithms were enabled. Since then, we recorded emission from four magnetar sources; of these, only one was an old magnetar: SGR 1806+20. The other three detections were two brand new sources, SGR J0501+4516, discovered with Swift and extensively monitored with both Swift and GBM, SGR J0418+5729, discovered with GBM and the Interplanetary Network (IPN), and SGR J1550-5418, a source originally classified as an Anomalous X-ray Pulsar (AXP 1E1547.0-5408). In my talk I will give a short history of the discovery of magnetars and describe how this, once relatively esoteric field, has emerged as a link between several astrophysical areas including Gamma-Ray Bursts. Finally, I will describe the properties of these sources and the current status of our knowledge of the magnetar population and birth rate.

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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Discovery of Massive, Mostly Star Formation Quenched Galaxies with Extremely Large Lyα Equivalent Widths at z ˜ 3

NASA Astrophysics Data System (ADS)

Taniguchi, Yoshiaki; Kajisawa, Masaru; Kobayashi, Masakazu A. R.; Nagao, Tohru; Shioya, Yasuhiro; Scoville, Nick Z.; Sanders, David B.; Capak, Peter L.; Koekemoer, Anton M.; Toft, Sune; McCracken, Henry J.; Le Fèvre, Olivier; Tasca, Lidia; Sheth, Kartik; Renzini, Alvio; Lilly, Simon; Carollo, Marcella; Kovač, Katarina; Ilbert, Olivier; Schinnerer, Eva; Fu, Hai; Tresse, Laurence; Griffiths, Richard E.; Civano, Francesca

2015-08-01

We report a discovery of six massive galaxies with both extremely large Lyα equivalent widths (EWs) and evolved stellar populations at z ˜ 3. These MAssive Extremely STrong Lyα emitting Objects (MAESTLOs) have been discovered in our large-volume systematic survey for strong Lyα emitters (LAEs) with 12 optical intermediate-band data taken with Subaru/Suprime-Cam in the COSMOS field. Based on the spectral energy distribution fitting analysis for these LAEs, it is found that these MAESTLOs have (1) large rest-frame EWs of EW0 (Lyα) ˜ 100-300 Å, (2) M⋆ ˜ 1010.5-1011.1 M⊙, and (3) relatively low specific star formation rates of SFR/M⋆ ˜ 0.03-1 Gyr-1. Three of the six MAESTLOs have extended Lyα emission with a radius of several kiloparsecs, although they show very compact morphology in the HST/ACS images, which correspond to the rest-frame UV continuum. Since the MAESTLOs do not show any evidence for active galactic nuclei, the observed extended Lyα emission is likely to be caused by a star formation process including the superwind activity. We suggest that this new class of LAEs, MAESTLOs, provides a missing link from star-forming to passively evolving galaxies at the peak era of the cosmic star formation history. Based on observations with NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by AURA, Inc., under NASA contract NAS 5-26555; also based on data collected at the Subaru Telescope, which is operated by the National Astronomical Observatory of Japan; and also based on data products from observations made with ESO Telescopes at the La Silla Paranal Observatory under ESO programme ID 179.A-2005 and on data products produced by TERAPIX and the Cambridge Astronomy Survey Unit on behalf of the UltraVISTA consortium.

Assessment of composite motif discovery methods.

PubMed

Klepper, Kjetil; Sandve, Geir K; Abul, Osman; Johansen, Jostein; Drablos, Finn

2008-02-26

Computational discovery of regulatory elements is an important area of bioinformatics research and more than a hundred motif discovery methods have been published. Traditionally, most of these methods have addressed the problem of single motif discovery - discovering binding motifs for individual transcription factors. In higher organisms, however, transcription factors usually act in combination with nearby bound factors to induce specific regulatory behaviours. Hence, recent focus has shifted from single motifs to the discovery of sets of motifs bound by multiple cooperating transcription factors, so called composite motifs or cis-regulatory modules. Given the large number and diversity of methods available, independent assessment of methods becomes important. Although there have been several benchmark studies of single motif discovery, no similar studies have previously been conducted concerning composite motif discovery. We have developed a benchmarking framework for composite motif discovery and used it to evaluate the performance of eight published module discovery tools. Benchmark datasets were constructed based on real genomic sequences containing experimentally verified regulatory modules, and the module discovery programs were asked to predict both the locations of these modules and to specify the single motifs involved. To aid the programs in their search, we provided position weight matrices corresponding to the binding motifs of the transcription factors involved. In addition, selections of decoy matrices were mixed with the genuine matrices on one dataset to test the response of programs to varying levels of noise. Although some of the methods tested tended to score somewhat better than others overall, there were still large variations between individual datasets and no single method performed consistently better than the rest in all situations. The variation in performance on individual datasets also shows that the new benchmark datasets represents a

Cheminformatics in Drug Discovery, an Industrial Perspective.

PubMed

Chen, Hongming; Kogej, Thierry; Engkvist, Ola

2018-05-18

Cheminformatics has established itself as a core discipline within large scale drug discovery operations. It would be impossible to handle the amount of data generated today in a small molecule drug discovery project without persons skilled in cheminformatics. In addition, due to increased emphasis on "Big Data", machine learning and artificial intelligence, not only in the society in general, but also in drug discovery, it is expected that the cheminformatics field will be even more important in the future. Traditional areas like virtual screening, library design and high-throughput screening analysis are highlighted in this review. Applying machine learning in drug discovery is an area that has become very important. Applications of machine learning in early drug discovery has been extended from predicting ADME properties and target activity to tasks like de novo molecular design and prediction of chemical reactions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

k-neighborhood Decentralization: A Comprehensive Solution to Index the UMLS for Large Scale Knowledge Discovery

PubMed Central

Xiang, Yang; Lu, Kewei; James, Stephen L.; Borlawsky, Tara B.; Huang, Kun; Payne, Philip R.O.

2011-01-01

The Unified Medical Language System (UMLS) is the largest thesaurus in the biomedical informatics domain. Previous works have shown that knowledge constructs comprised of transitively-associated UMLS concepts are effective for discovering potentially novel biomedical hypotheses. However, the extremely large size of the UMLS becomes a major challenge for these applications. To address this problem, we designed a k-neighborhood Decentralization Labeling Scheme (kDLS) for the UMLS, and the corresponding method to effectively evaluate the kDLS indexing results. kDLS provides a comprehensive solution for indexing the UMLS for very efficient large scale knowledge discovery. We demonstrated that it is highly effective to use kDLS paths to prioritize disease-gene relations across the whole genome, with extremely high fold-enrichment values. To our knowledge, this is the first indexing scheme capable of supporting efficient large scale knowledge discovery on the UMLS as a whole. Our expectation is that kDLS will become a vital engine for retrieving information and generating hypotheses from the UMLS for future medical informatics applications. PMID:22154838

k-Neighborhood decentralization: a comprehensive solution to index the UMLS for large scale knowledge discovery.

PubMed

Xiang, Yang; Lu, Kewei; James, Stephen L; Borlawsky, Tara B; Huang, Kun; Payne, Philip R O

2012-04-01

The Unified Medical Language System (UMLS) is the largest thesaurus in the biomedical informatics domain. Previous works have shown that knowledge constructs comprised of transitively-associated UMLS concepts are effective for discovering potentially novel biomedical hypotheses. However, the extremely large size of the UMLS becomes a major challenge for these applications. To address this problem, we designed a k-neighborhood Decentralization Labeling Scheme (kDLS) for the UMLS, and the corresponding method to effectively evaluate the kDLS indexing results. kDLS provides a comprehensive solution for indexing the UMLS for very efficient large scale knowledge discovery. We demonstrated that it is highly effective to use kDLS paths to prioritize disease-gene relations across the whole genome, with extremely high fold-enrichment values. To our knowledge, this is the first indexing scheme capable of supporting efficient large scale knowledge discovery on the UMLS as a whole. Our expectation is that kDLS will become a vital engine for retrieving information and generating hypotheses from the UMLS for future medical informatics applications. Copyright © 2011 Elsevier Inc. All rights reserved.

The Discovery of a Microarcsecond Quasar: J1819+3845.

PubMed

Dennett-Thorpe; de Bruyn AG

2000-02-01

We report on the discovery of a source that exhibits over 300% amplitude changes in radio flux density on the period of hours. This source, J1819+3845, is the most extremely variable extragalactic source known in the radio sky. We believe these properties are due to interstellar scintillation and show that the source must emit at least 55% of its flux density within a radius of fewer than 16 µas at 5 GHz. The apparent brightness temperature is greater than 5x1012 K, and the source may be explained by a relativistically moving source with a Doppler factor of approximately 15. The scattering occurs predominantly in material only a few tens of parsecs from the Earth, which explains its unusually rapid variability. If the source PKS 0405-385 is similarly affected by local scattering material, Doppler factors of approximately 1000 are not required to explain this source. The discovery of a second source whose properties are well modeled by interstellar scintillation strengthens the argument for this as the cause for much of the variation seen in intraday variables.

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.

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.

10 CFR 590.305 - Informal discovery.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Informal discovery. 590.305 Section 590.305 Energy DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Procedures § 590.305 Informal discovery. The...

Computational methods in drug discovery

PubMed Central

Leelananda, Sumudu P

2016-01-01

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

Computational methods in drug discovery.

PubMed

Leelananda, Sumudu P; Lindert, Steffen

2016-01-01

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

Analysis of the dependence of extreme rainfalls

NASA Astrophysics Data System (ADS)

Padoan, Simone; Ancey, Christophe; Parlange, Marc

2010-05-01

The aim of spatial analysis is to quantitatively describe the behavior of environmental phenomena such as precipitation levels, wind speed or daily temperatures. A number of generic approaches to spatial modeling have been developed[1], but these are not necessarily ideal for handling extremal aspects given their focus on mean process levels. The areal modelling of the extremes of a natural process observed at points in space is important in environmental statistics; for example, understanding extremal spatial rainfall is crucial in flood protection. In light of recent concerns over climate change, the use of robust mathematical and statistical methods for such analyses has grown in importance. Multivariate extreme value models and the class of maxstable processes [2] have a similar asymptotic motivation to the univariate Generalized Extreme Value (GEV) distribution , but providing a general approach to modeling extreme processes incorporating temporal or spatial dependence. Statistical methods for max-stable processes and data analyses of practical problems are discussed by [3] and [4]. This work illustrates methods to the statistical modelling of spatial extremes and gives examples of their use by means of a real extremal data analysis of Switzerland precipitation levels. [1] Cressie, N. A. C. (1993). Statistics for Spatial Data. Wiley, New York. [2] de Haan, L and Ferreria A. (2006). Extreme Value Theory An Introduction. Springer, USA. [3] Padoan, S. A., Ribatet, M and Sisson, S. A. (2009). Likelihood-Based Inference for Max-Stable Processes. Journal of the American Statistical Association, Theory & Methods. In press. [4] Davison, A. C. and Gholamrezaee, M. (2009), Geostatistics of extremes. Journal of the Royal Statistical Society, Series B. To appear.

What Does Galileo's Discovery of Jupiter's Moons Tell Us About the Process of Scientific Discovery?

NASA Astrophysics Data System (ADS)

Lawson, Anton E.

In 1610, Galileo Galilei discovered Jupiter''smoons with the aid of a new morepowerful telescope of his invention. Analysisof his report reveals that his discoveryinvolved the use of at least three cycles ofhypothetico-deductive reasoning. Galileofirst used hypothetico-deductive reasoning to generateand reject a fixed star hypothesis.He then generated and rejected an ad hocastronomers-made-a-mistake hypothesis.Finally, he generated, tested, and accepted a moonhypothesis. Galileo''s reasoningis modeled in terms of Piaget''s equilibration theory,Grossberg''s theory of neurologicalactivity, a neural network model proposed by Levine &Prueitt, and another proposedby Kosslyn & Koenig. Given that hypothetico-deductivereasoning has played a rolein other important scientific discoveries, thequestion is asked whether it plays a rolein all important scientific discoveries. In otherwords, is hypothetico-deductive reasoningthe essence of the scientific method? Possiblealternative scientific methods, such asBaconian induction and combinatorial analysis,are explored and rejected as viablealternatives. Educational implications of thishypothetico-deductive view of scienceare discussed.

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

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.

Mitigating risk in academic preclinical drug discovery

PubMed Central

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

2018-01-01

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

The future of discovery chemistry: quo vadis? Academic to industrial--the maturation of medicinal chemistry to chemical biology.

PubMed

Hoffmann, Torsten; Bishop, Cheryl

2010-04-01

At Roche, we set out to think about the future role of medicinal chemistry in drug discovery in a project involving both Roche internal stakeholders and external experts in drug discovery chemistry. To derive a coherent strategy, selected scientists were asked to take extreme positions and to derive two orthogonal strategic options: chemistry as the traditional mainstream science and chemistry as the central entrepreneurial science. We believe today's role of medicinal chemistry in industry has remained too narrow. To provide the innovation that industry requires, medicinal chemistry must play its part and diversify at pace with our increasing understanding of chemical biology and network pharmacology. 2010 Elsevier Ltd. All rights reserved.

Space Shuttle Discovery lifts off successfully

NASA Technical Reports Server (NTRS)

1998-01-01

Clouds of exhaust seem to fill the marsh near Launch Pad 39B as Space Shuttle Discovery lifts off at 2:19 p.m. EST Oct. 29 on mission STS-95. Making his second voyage into space after 36 years is Payload Specialist John H. Glenn Jr., senator from Ohio. Other crew members are Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Payload Specialist Chiaki Mukai, (M.D., Ph.D.), with the National Space Development Agency of Japan (NASDA), Mission Specialist Stephen K. Robinson, Mission Specialist Pedro Duque of Spain, representing the European Space Agency (ESA), and Mission Specialist Scott E. Parazynski. The STS-95 mission includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process. Discovery is expected to return to KSC at 11:49 a.m. EST on Nov. 7.

Space Shuttle Discovery lifts off successfully

NASA Technical Reports Server (NTRS)

1998-01-01

Tree branches on the Space Coast frame Space Shuttle Discovery's liftoff from Launch Pad 39B at 2:19 p.m. EST Oct. 29 on mission STS-95. Making his second voyage into space after 36 years is Payload Specialist John H. Glenn Jr., senator from Ohio. Other crew members are Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Payload Specialist Chiaki Mukai, (M.D., Ph.D.), with the National Space Development Agency of Japan (NASDA), Mission Specialist Stephen K. Robinson, Mission Specialist Pedro Duque of Spain, representing the European Space Agency (ESA), and Mission Specialist Scott E. Parazynski. The STS-95 mission includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process. Discovery is expected to return to KSC at 11:49 a.m. EST on Nov. 7.

Space Shuttle Discovery lifts off successfully

NASA Technical Reports Server (NTRS)

1998-01-01

Clouds of exhaust and blazing light fill Launch Pad 39B as Space Shuttle Discovery lifts off at 2:19 p.m. EST Oct. 29 on mission STS-95. Making his second voyage into space after 36 years is Payload Specialist John H. Glenn Jr., senator from Ohio. Other crew members are Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Payload Specialist Chiaki Mukai, (M.D., Ph.D.), with the National Space Development Agency of Japan (NASDA), Mission Specialist Stephen K. Robinson, Mission Specialist Pedro Duque of Spain, representing the European Space Agency (ESA), and Mission Specialist Scott E. Parazynski. The STS-95 mission includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process. Discovery is expected to return to KSC at 11:49 a.m. EST on Nov. 7.

Space Shuttle Discovery lifts off successfully

NASA Technical Reports Server (NTRS)

1998-01-01

Space Shuttle Discovery clears Launch Pad 39B at 2:19 p.m. EST Oct. 29 as it lifts off on mission STS-95. Making his second voyage into space after 36 years is Payload Specialist John H. Glenn Jr., senator from Ohio. Other crew members are Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Payload Specialist Chiaki Mukai, (M.D., Ph.D.), with the National Space Development Agency of Japan (NASDA), Mission Specialist Stephen K. Robinson, Mission Specialist Pedro Duque of Spain, representing the European Space Agency (ESA), and Mission Specialist Scott E. Parazynski. The STS-95 mission includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process. Discovery is expected to return to KSC at 11:49 a.m. EST on Nov. 7.

Accelerating the Rate of Astronomical Discovery

NASA Astrophysics Data System (ADS)

Norris, Ray P. Ruggles, Clive L. N.

2010-05-01

Special Session 5 on Accelerating the Rate of Astronomical Discovery addressed a range of potential limits to progress - paradigmatic, technological, organisational, and political - examining each issue both from modern and historical perspectives, and drawing lessons to guide future progress. A number of issues were identified which potentially regulate the flow of discoveries, such as the balance between large strongly-focussed projects and instruments, designed to answer the most fundamental questions confronting us, and the need to maintain a creative environment with room for unorthodox thinkers and bold, high risk, projects. Also important is the need to maintain historical and cultural perspectives, and the need to engage the minds of the most brilliant young people on the planet, regardless of their background, ethnicity, gender, or geography.

XVis: Visualization for the Extreme-Scale Scientific-Computation Ecosystem: Year-end report FY17.

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

Moreland, Kenneth D.; Pugmire, David; Rogers, David

The XVis project brings together the key elements of research to enable scientific discovery at extreme scale. Scientific computing will no longer be purely about how fast computations can be performed. Energy constraints, processor changes, and I/O limitations necessitate significant changes in both the software applications used in scientific computation and the ways in which scientists use them. Components for modeling, simulation, analysis, and visualization must work together in a computational ecosystem, rather than working independently as they have in the past. This project provides the necessary research and infrastructure for scientific discovery in this new computational ecosystem by addressingmore » four interlocking challenges: emerging processor technology, in situ integration, usability, and proxy analysis.« less

STS-51 Discovery launch

NASA Image and Video Library

1993-09-12

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

Evaluating Discovery Services Architectures in the Context of the Internet of Things

NASA Astrophysics Data System (ADS)

Polytarchos, Elias; Eliakis, Stelios; Bochtis, Dimitris; Pramatari, Katerina

As the "Internet of Things" is expected to grow rapidly in the following years, the need to develop and deploy efficient and scalable Discovery Services in this context is very important for its success. Thus, the ability to evaluate and compare the performance of different Discovery Services architectures is vital if we want to allege that a given design is better at meeting requirements of a specific application. The purpose of this chapter is to provide a paradigm for the evaluation of different Discovery Services for the Internet of Things in terms of efficiency, scalability and performance through the use of simulations. The methodology presented uses the application of Discovery Services to a supply chain with the Service Lookup Service Discovery Service using OMNeT++, an open source network simulation suite. Then, we delve into the simulation design and the details of our findings.

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. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Search strategy has influenced the discovery rate of human viruses.

PubMed

Rosenberg, Ronald; Johansson, Michael A; Powers, Ann M; Miller, Barry R

2013-08-20

A widely held concern is that the pace of infectious disease emergence has been increasing. We have analyzed the rate of discovery of pathogenic viruses, the preeminent source of newly discovered causes of human disease, from 1897 through 2010. The rate was highest during 1950-1969, after which it moderated. This general picture masks two distinct trends: for arthropod-borne viruses, which comprised 39% of pathogenic viruses, the discovery rate peaked at three per year during 1960-1969, but subsequently fell nearly to zero by 1980; however, the rate of discovery of nonarboviruses remained stable at about two per year from 1950 through 2010. The period of highest arbovirus discovery coincided with a comprehensive program supported by The Rockefeller Foundation of isolating viruses from humans, animals, and arthropod vectors at field stations in Latin America, Africa, and India. The productivity of this strategy illustrates the importance of location, approach, long-term commitment, and sponsorship in the discovery of emerging pathogens.

Science beyond boundary: are premature discoveries things of the past?

PubMed

Singh, Rama S

2016-06-01

Mendel's name more than of any other draws our attention to the personal side in terms of success and failure in science. Mendel lived 19 years after presenting his research findings and died without receiving any recognition for his work. Are premature discoveries things of the past, you may ask? I review the material basis of science in terms of science boundary and field accessibility and analyze the possibility of premature discoveries in different fields of science such as, for example, physics and biology. I conclude that science has reached a stage where progress is being made mostly by pushing the boundary of the known from inside than by leaping across boundaries. As more researchers become engaged in science, and as more publications become open access, on-line, and interactive, the probability of an important discovery remaining buried and going unrecognized would become exceedingly small. Of course, as examples from physics show, a new theory or an important idea can always lie low, unrecognized until it becomes re-discovered and popularized by other researchers. Thus, premature discoveries will become less likely but not forbidden.

The Neutron's Discovery - 80 Years on

NASA Astrophysics Data System (ADS)

Rogers, John D.

A brief review is given of selected highlights in scientific developments from the birth of modern nuclear physics at the end of the 19th century to the discovery of the neutron in 1932. This is followed by some important milestones in neutron and reactor physics that have led to our current understanding and implementation of nuclear technologies. The beginnings can be traced back to the discovery of X-rays by Roentgen, the identification of natural radioactivity by Becquerel and the discovery of the electron by Thomson, towards the end of the 19th Century. Rutherford was a key figure in experimental physics who determined the structure of the atom and who inspired his students at McGill, Manchester and Cambridge Universities (many of whom would become Nobel laureates) in the pursuit of their physics research. One of Rutherford's students, James Chadwick, had studied the work carried out by Bothe and Becker on alpha particle-induced disintegration of light elements which had led to their observation of high energy penetrating radiation that neither they nor the Joliot-Curies could identify. Chadwick knew that the only possible explanation was the emission of a neutron in the nuclear reaction. He carried out tests in the Cavendish Laboratory and submitted his now classical paper identifying the neutron to the periodical Nature in 1932. The discovery of the neutron and of nuclear fission in 1939 opened up new areas for scientific investigation, in, for example, astrophysics, geology, neutron and nuclear physics. The prospects for nuclear power in particular appeared to be unlimited and both civil and military applications have been actively pursued. Many new experimental facilities have been designed and built to provide intense sources of neutrons for research purposes. Work carried out in such centres is included in the programme of the 7th International Topical Meeting on Neutron Radiography, an important forum for discussion of the latest research work of this

Analysis of the extreme diversity of salivary alpha-amylase isoforms generated by physiological proteolysis using liquid chromatography-tandem mass spectrometry.

PubMed

Bailey, Ulla-Maja; Punyadeera, Chamindie; Cooper-White, Justin J; Schulz, Benjamin L

2012-12-12

Saliva is a crucial biofluid for oral health and is also of increasing importance as a non-invasive source of disease biomarkers. Salivary alpha-amylase is an abundant protein in saliva, and changes in amylase expression have been previously associated with a variety of diseases and conditions. Salivary alpha-amylase is subject to a high diversity of post-translational modifications, including physiological proteolysis in the oral cavity. Here we developed methodology for rapid sample preparation and non-targeted LC-ESI-MS/MS analysis of saliva from healthy subjects and observed an extreme diversity of alpha-amylase proteolytic isoforms. Our results emphasize the importance of consideration of post-translational events such as proteolysis in proteomic studies, biomarker discovery and validation, particularly in saliva. Copyright © 2012 Elsevier B.V. All rights reserved.

High Tc: The Discovery of RBCO

NASA Astrophysics Data System (ADS)

Chu, C. W.

2007-03-01

It was said by Emerson that ``there is no history; there is only biography.'' This is especially true when the events are recounted by a person who, himself, has been heavily involved and the line between history and autobiography can become blurred. However, it is reasonable to say that discovery itself is not a series of accidents but an inevitable product of each development stage of scientific knowledge as was also pointed out by Holden et al. (1) The discovery of RBCO (2,3) with R = Y, La, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu is no exception. In this presentation, I will briefly recount several events that were crucial to the discovery of RBCO: those before 1986 (4) that sowed the seeds in our group important to our later high temperature superconductivity effort; those in 1986 (5) that were critical to our discovery of the 93 K RBCO soon after the discovery of the 35 K high temperature superconductor by M"uller and Bednorz (6); and those in 1987 when the barrier of the liquid nitrogen boiling temperature of 77 K was finally conquered. 1. G. J. Holton et al., American Scientist 84, 364 (1996). 2. M. K. Wu et al., Phys. Rev. Lett. 58, 908 (1987). 3. P. H. Hor et al., Phys. Rev. Lett. 58, 1891 (1987). 4. C. W. Chu et al., S. S. Comm. 18, 977 (1976); C. W. Chu and V. Diatchenko, Phys. Rev. Lett. 41, 572 (1978); T. H. Lin et al., Phys. Rev. B(RC) 29, 1493 (1984); J. H. Lin et al., J. Low Temp. Phys. 58, 363 (1985). 5. C. W. Chu et al., Phys. Rev. Lett. 58, 405 (1987); C. W. Chu et al., Science 235, 567 (1987). 6. J. G. Bednorz and K. A. M"uller, Z. Phys. B64, 189 (1986).

PANORAMA: An approach to performance modeling and diagnosis of extreme-scale workflows

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

Deelman, Ewa; Carothers, Christopher; Mandal, Anirban

Here we report that computational science is well established as the third pillar of scientific discovery and is on par with experimentation and theory. However, as we move closer toward the ability to execute exascale calculations and process the ensuing extreme-scale amounts of data produced by both experiments and computations alike, the complexity of managing the compute and data analysis tasks has grown beyond the capabilities of domain scientists. Therefore, workflow management systems are absolutely necessary to ensure current and future scientific discoveries. A key research question for these workflow management systems concerns the performance optimization of complex calculation andmore » data analysis tasks. The central contribution of this article is a description of the PANORAMA approach for modeling and diagnosing the run-time performance of complex scientific workflows. This approach integrates extreme-scale systems testbed experimentation, structured analytical modeling, and parallel systems simulation into a comprehensive workflow framework called Pegasus for understanding and improving the overall performance of complex scientific workflows.« less

PANORAMA: An approach to performance modeling and diagnosis of extreme-scale workflows

DOE PAGES

Deelman, Ewa; Carothers, Christopher; Mandal, Anirban; ...

2015-07-14

Here we report that computational science is well established as the third pillar of scientific discovery and is on par with experimentation and theory. However, as we move closer toward the ability to execute exascale calculations and process the ensuing extreme-scale amounts of data produced by both experiments and computations alike, the complexity of managing the compute and data analysis tasks has grown beyond the capabilities of domain scientists. Therefore, workflow management systems are absolutely necessary to ensure current and future scientific discoveries. A key research question for these workflow management systems concerns the performance optimization of complex calculation andmore » data analysis tasks. The central contribution of this article is a description of the PANORAMA approach for modeling and diagnosing the run-time performance of complex scientific workflows. This approach integrates extreme-scale systems testbed experimentation, structured analytical modeling, and parallel systems simulation into a comprehensive workflow framework called Pegasus for understanding and improving the overall performance of complex scientific workflows.« less

Discovery touches down after successful mission STS-95

NASA Technical Reports Server (NTRS)

1998-01-01

After nine days and 3.6 million miles in space, orbiter Discovery prepares to land on runway 33 at the Shuttle Landing Facility. Discovery returns to Earth with its crew of seven after successfully completing mission STS-95. The STS-95 crew members are Mission Commander Curtis L. Brown Jr.; Pilot Steven W. Lindsey; Mission Specialist Scott E. Parazynski; Mission Specialist Stephen K. Robinson; Payload Specialist John H. Glenn Jr., a senator from Ohio; Mission Specialist Pedro Duque of Spain, with the European Space Agency (ESA); and Payload Specialist Chiaki Mukai, with the National Space Development Agency of Japan (NASDA). The mission included research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

Discovery touches down after successful mission STS-95

NASA Technical Reports Server (NTRS)

1998-01-01

Orbiter Discovery lowers its nose wheel after touching down on runway 33 at the Shuttle Landing Facility. Discovery returns to Earth with its crew of seven after successfully completing mission STS-95, lasting nearly nine days and 3.6 million miles. The STS-95 crew is composed of Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Mission Specialist Scott E. Parazynski, Mission Specialist Stephen K. Robinson, Payload Specialist John H. Glenn Jr., senator from Ohio, Mission Specialist Pedro Duque, with the European Space Agency (ESA), and Payload Specialist Chiaki Mukai, with the National Space Development Agency of Japan (NASDA). The mission included research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

Discovery touches down after successful mission STS-95

NASA Technical Reports Server (NTRS)

1998-01-01

Orbiter Discovery touches down in a cloud of smoke on runway 33 at the Shuttle Landing Facility. Discovery returns to Earth with its crew of seven after successfully completing mission STS-95, lasting nearly nine days and 3.6 million miles. The crew members are Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Mission Specialist Scott E. Parazynski, Mission Specialist Stephen K. Robinson, Payload Specialist John H. Glenn Jr., senator from Ohio, Mission Specialist Pedro Duque, with the European Space Agency (ESA), and Payload Specialist Chiaki Mukai, with the National Space Development Agency of Japan (NASDA). The mission included research payloads such as the Spartan solar- observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

Extreme Environment Simulation - Current and New Capabilities to Simulate Venus and Other Planetary Bodies

NASA Technical Reports Server (NTRS)

Kremic, Tibor; Vento, Dan; Lalli, Nick; Palinski, Timothy

2014-01-01

Science, technology, and planetary mission communities have a growing interest in components and systems that are capable of working in extreme (high) temperature and pressure conditions. Terrestrial applications range from scientific research, aerospace, defense, automotive systems, energy storage and power distribution, deep mining and others. As the target environments get increasingly extreme, capabilities to develop and test the sensors and systems designed to operate in such environments will be required. An application of particular importance to the planetary science community is the ability for a robotic lander to survive on the Venus surface where pressures are nearly 100 times that of Earth and temperatures approach 500C. The scientific importance and relevance of Venus missions are stated in the current Planetary Decadal Survey. Further, several missions to Venus were proposed in the most recent Discovery call. Despite this interest, the ability to accurately simulate Venus conditions at a scale that can test and validate instruments and spacecraft systems and accurately simulate the Venus atmosphere has been lacking. This paper discusses and compares the capabilities that are known to exist within and outside the United States to simulate the extreme environmental conditions found in terrestrial or planetary surfaces including the Venus atmosphere and surface. The paper then focuses on discussing the recent additional capability found in the NASA Glenn Extreme Environment Rig (GEER). The GEER, located at the NASA Glenn Research Center in Cleveland, Ohio, is designed to simulate not only the temperature and pressure extremes described, but can also accurately reproduce the atmospheric compositions of bodies in the solar system including those with acidic and hazardous elements. GEER capabilities and characteristics are described along with operational considerations relevant to potential users. The paper presents initial operating results and concludes

Extreme droughts affecting Mediterranean tree species' growth and water-use efficiency: the importance of timing.

PubMed

Forner, Alicia; Valladares, Fernando; Bonal, Damien; Granier, André; Grossiord, Charlotte; Aranda, Ismael

2018-03-15

It has been known for a long time that drought intensity is a critical variable in determining water stress of Mediterranean tree species. However, not as much attention has been paid to other drought characteristics, for example the timing of the dry periods. We investigated the impact of the timing and intensity of extreme droughts on growing season length, growth and water-use efficiency of three tree species, Pinus nigra ssp. Salzmannii J.F. Arnold, Quercus ilex ssp. ballota (Desf.) Samp. and Quercus faginea Lam. coexisting in a continental Mediterranean ecosystem. Over the study period (2009-13), intense droughts were observed at annual and seasonal scales, particularly during 2011 and 2012. In 2012, an atypically dry winter and spring was followed by an intense summer drought. Quercus faginea growth was affected more by drought timing than by drought intensity, probably because of its winter-deciduous leaf habit. Pinus nigra showed a lower decrease in secondary growth than observed in the two Quercus species in extremely dry years. Resilience to extreme droughts was different among species, with Q. faginea showing poorer recovery of growth after very dry years. The highest intra- and inter-annual plasticity in water-use efficiency was observed in P. nigra, which maintained a more water-saving strategy. Our results revealed that the timing of extreme drought events can affect tree function to a larger extent than drought intensity, especially in deciduous species. Legacy effects of drought over months and years significantly strengthened the impact of drought timing and intensity on tree function.

Life in hot acid: Pathway analyses in extremely thermoacidophilic archaea

PubMed Central

Auernik, Kathryne S.; Cooper, Charlotte R.; Kelly, Robert M.

2013-01-01

SUMMARY The extremely thermoacidophilic archaea are a particularly intriguing group of microorganisms that must simultaneously cope with biologically extreme pHs (≤ 4) and temperatures (Topt ≥ 60°C) in their natural environments. Their expandi ng biotechnological significance relates to their role in biomining of base and precious metals and their unique mechanisms of survival in hot acid, at both the cellular and biomolecular levels. Recent developments, such as advances in understanding of heavy metal tolerance mechanisms, implementation of a genetic system, and discovery of a new carbon fixation pathway, have been facilitated by availability of genome sequence data and molecular genetic systems. As a result, new insights into the metabolic pathways and physiological features that define extreme thermoacidophily have been obtained, in some cases suggesting prospects for biotechnological opportunities. PMID:18760359

How extreme is extreme hourly precipitation?

NASA Astrophysics Data System (ADS)

Papalexiou, Simon Michael; Dialynas, Yannis G.; Pappas, Christoforos

2016-04-01

The importance of accurate representation of precipitation at fine time scales (e.g., hourly), directly associated with flash flood events, is crucial in hydrological design and prediction. The upper part of a probability distribution, known as the distribution tail, determines the behavior of extreme events. In general, and loosely speaking, tails can be categorized in two families: the subexponential and the hyperexponential family, with the first generating more intense and more frequent extremes compared to the latter. In past studies, the focus has been mainly on daily precipitation, with the Gamma distribution being the most popular model. Here, we investigate the behaviour of tails of hourly precipitation by comparing the upper part of empirical distributions of thousands of records with three general types of tails corresponding to the Pareto, Lognormal, and Weibull distributions. Specifically, we use thousands of hourly rainfall records from all over the USA. The analysis indicates that heavier-tailed distributions describe better the observed hourly rainfall extremes in comparison to lighter tails. Traditional representations of the marginal distribution of hourly rainfall may significantly deviate from observed behaviours of extremes, with direct implications on hydroclimatic variables modelling and engineering design.

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.

Space Shuttle Discovery lifts off successfully

NASA Technical Reports Server (NTRS)

1998-01-01

Framed by the foliage of the Canaveral National Sea Shore, Space Shuttle Discovery soars through bright blue skies as it lifts off from Launch Pad 39B at 2:19 p.m. EST Oct. 29 on mission STS-95. Making his second voyage into space after 36 years is Payload Specialist John H. Glenn Jr., senator from Ohio. Other crew members are Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Payload Specialist Chiaki Mukai, (M.D., Ph.D.), with the National agency for Space Development (NASDA), Mission Specialist Stephen K. Robinson, Mission Specialist Pedro Duque of Spain, representing the European Space Agency (ESA), and Mission Specialist Scott E. Parazynski. The STS-95 mission includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process. Discovery is expected to return to KSC at 11:49 a.m. EST on Nov. 7.

Extremely frequency-widened terahertz wave generation using Cherenkov-type radiation.

PubMed

Suizu, Koji; Koketsu, Kaoru; Shibuya, Takayuki; Tsutsui, Toshihiro; Akiba, Takuya; Kawase, Kodo

2009-04-13

Terahertz (THz) wave generation based on nonlinear frequency conversion is promising way for realizing a tunable monochromatic bright THz-wave source. Such a development of efficient and wide tunable THz-wave source depends on discovery of novel brilliant nonlinear crystal. Important factors of a nonlinear crystal for THz-wave generation are, 1. High nonlinearity and 2. Good transparency at THz frequency region. Unfortunately, many nonlinear crystals have strong absorption at THz frequency region. The fact limits efficient and wide tunable THz-wave generation. Here, we show that Cherenkov radiation with waveguide structure is an effective strategy for achieving efficient and extremely wide tunable THz-wave source. We fabricated MgO-doped lithium niobate slab waveguide with 3.8 microm of thickness and demonstrated difference frequency generation of THz-wave generation with Cherenkov phase matching. Extremely frequency-widened THz-wave generation, from 0.1 to 7.2 THz, without no structural dips successfully obtained. The tuning frequency range of waveguided Cherenkov radiation source was extremely widened compare to that of injection seeded-Terahertz Parametric Generator. The tuning range obtained in this work for THz-wave generation using lithium niobate crystal was the widest value in our knowledge. The highest THz-wave energy obtained was about 3.2 pJ, and the energy conversion efficiency was about 10(-5) %. The method can be easily applied for many conventional nonlinear crystals, results in realizing simple, reasonable, compact, high efficient and ultra broad band THz-wave sources.

Metabolomics for Biomarker Discovery: Moving to the Clinic

PubMed Central

Zhang, Aihua; Sun, Hui; Yan, Guangli; Wang, Ping; Wang, Xijun

2015-01-01

To improve the clinical course of diseases, more accurate diagnostic and assessment methods are required as early as possible. In order to achieve this, metabolomics offers new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has become an important tool in clinical research and the diagnosis of human disease and has been applied to discovery and identification of the perturbed pathways. It provides a powerful approach to discover biomarkers in biological systems and offers a holistic approach with the promise to clinically enhance diagnostics. When carried out properly, it could provide insight into the understanding of the underlying mechanisms of diseases, help to identify patients at risk of disease, and predict the response to specific treatments. Currently, metabolomics has become an important tool in clinical research and the diagnosis of human disease and becomes a hot topic. This review will highlight the importance and benefit of metabolomics for identifying biomarkers that accurately screen potential biomarkers of diseases. PMID:26090402

Discovery of a population of bulgeless galaxies with extremely red MID-IR colors: Obscured AGN activity in the low-mass regime?

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

Satyapal, S.; Secrest, N. J.; McAlpine, W.

2014-04-01

In contrast to massive, bulge hosting galaxies, very few supermassive black holes (SMBHs) are known in either low-mass or bulgeless galaxies. Such a population could provide clues to the origins of SMBHs and to secular pathways for their growth. Using the all-sky Wide-field Infrared Survey Explorer (WISE ) survey, and bulge-to-disk decompositions from the Sloan Digital Sky Survey (SDSS) Data Release 7, we report the discovery of a population of local (z < 0.3) bulgeless disk galaxies with extremely red mid-infrared colors which are highly suggestive of a dominant active galactic nucleus (AGN), despite having no optical AGN signatures inmore » their SDSS spectra. Using various mid-infrared selection criteria from the literature, there are between 30 and over 300 bulgeless galaxies with possible AGNs. Other known scenarios that can heat the dust to high temperatures do not appear to explain the observed colors of this sample. If these galaxies are confirmed to host AGNs, this study will provide a breakthrough in characterizing the properties of SMBHs in the low bulge mass regime and in understanding their relation with their host galaxies. Mid-infrared selection identifies AGNs that dominate their host galaxy's emission and therefore reveal a different AGN population than that uncovered by optical studies. We find that the fraction of all galaxies identified as candidate AGNs by WISE is highest at lower stellar masses and drops dramatically in higher mass galaxies, in striking contrast to the findings from optical studies.« less

Network-based discovery through mechanistic systems biology. Implications for applications--SMEs and drug discovery: where the action is.

PubMed

Benson, Neil

2015-08-01

Phase II attrition remains the most important challenge for drug discovery. Tackling the problem requires improved understanding of the complexity of disease biology. Systems biology approaches to this problem can, in principle, deliver this. This article reviews the reports of the application of mechanistic systems models to drug discovery questions and discusses the added value. Although we are on the journey to the virtual human, the length, path and rate of learning from this remain an open question. Success will be dependent on the will to invest and make the most of the insight generated along the way. Copyright © 2015 Elsevier Ltd. All rights reserved.

The future of quantum dots in drug discovery.

PubMed

Lin, Guimiao; Yin, Feng; Yong, Ken-Tye

2014-09-01

The rapid development of drug discovery today is inseparable from the interaction of advanced particle technologies and new drug synthesis protocols. Quantum dots (QDs) are regarded as a unique class of fluorescent labels, with unique optical properties such as high brightness and long-term colloidal and optical stability; these are suitable for optical imaging, drug delivery and optical tracking, fluorescence immunoassay and other medicinal applications. More importantly, QD possesses a rich surface chemistry property that is useful for incorporating various drug molecules, targeting ligands, and additional contrast agents (e.g., MRI, PET, etc.) onto the nanoparticle surface for achieving targeted and traceable drug delivery therapy at both cellular and systemic levels. In recent times, the advancement of QD technology has promoted the use of functionalized nanocrystals for in vivo applications. Such research is paving the way for drug discovery using various bioconjugated QD formulations. In this editorial, the authors highlight the current research progress and future applications of QDs in drug discovery.

Quantifying the Ease of Scientific Discovery

PubMed Central

Arbesman, Samuel

2012-01-01

It has long been known that scientific output proceeds on an exponential increase, or more properly, a logistic growth curve. The interplay between effort and discovery is clear, and the nature of the functional form has been thought to be due to many changes in the scientific process over time. Here I show a quantitative method for examining the ease of scientific progress, another necessary component in understanding scientific discovery. Using examples from three different scientific disciplines – mammalian species, chemical elements, and minor planets – I find the ease of discovery to conform to an exponential decay. In addition, I show how the pace of scientific discovery can be best understood as the outcome of both scientific output and ease of discovery. A quantitative study of the ease of scientific discovery in the aggregate, such as done here, has the potential to provide a great deal of insight into both the nature of future discoveries and the technical processes behind discoveries in science. PMID:22328796

Quantifying the Ease of Scientific Discovery.

PubMed

Arbesman, Samuel

2011-02-01

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

XVis: Visualization for the Extreme-Scale Scientific-Computation Ecosystem: Mid-year report FY17 Q2

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

Moreland, Kenneth D.; Pugmire, David; Rogers, David

The XVis project brings together the key elements of research to enable scientific discovery at extreme scale. Scientific computing will no longer be purely about how fast computations can be performed. Energy constraints, processor changes, and I/O limitations necessitate significant changes in both the software applications used in scientific computation and the ways in which scientists use them. Components for modeling, simulation, analysis, and visualization must work together in a computational ecosystem, rather than working independently as they have in the past. This project provides the necessary research and infrastructure for scientific discovery in this new computational ecosystem by addressingmore » four interlocking challenges: emerging processor technology, in situ integration, usability, and proxy analysis.« less

XVis: Visualization for the Extreme-Scale Scientific-Computation Ecosystem. Mid-year report FY16 Q2

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

Moreland, Kenneth D.; Sewell, Christopher; Childs, Hank

The XVis project brings together the key elements of research to enable scientific discovery at extreme scale. Scientific computing will no longer be purely about how fast computations can be performed. Energy constraints, processor changes, and I/O limitations necessitate significant changes in both the software applications used in scientific computation and the ways in which scientists use them. Components for modeling, simulation, analysis, and visualization must work together in a computational ecosystem, rather than working independently as they have in the past. This project provides the necessary research and infrastructure for scientific discovery in this new computational ecosystem by addressingmore » four interlocking challenges: emerging processor technology, in situ integration, usability, and proxy analysis.« less

XVis: Visualization for the Extreme-Scale Scientific-Computation Ecosystem: Year-end report FY15 Q4.

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

Moreland, Kenneth D.; Sewell, Christopher; Childs, Hank

The XVis project brings together the key elements of research to enable scientific discovery at extreme scale. Scientific computing will no longer be purely about how fast computations can be performed. Energy constraints, processor changes, and I/O limitations necessitate significant changes in both the software applications used in scientific computation and the ways in which scientists use them. Components for modeling, simulation, analysis, and visualization must work together in a computational ecosystem, rather than working independently as they have in the past. This project provides the necessary research and infrastructure for scientific discovery in this new computational ecosystem by addressingmore » four interlocking challenges: emerging processor technology, in situ integration, usability, and proxy analysis.« less

Molecular dynamics-driven drug discovery: leaping forward with confidence.

PubMed

Ganesan, Aravindhan; Coote, Michelle L; Barakat, Khaled

2017-02-01

Given the significant time and financial costs of developing a commercial drug, it remains important to constantly reform the drug discovery pipeline with novel technologies that can narrow the candidates down to the most promising lead compounds for clinical testing. The past decade has witnessed tremendous growth in computational capabilities that enable in silico approaches to expedite drug discovery processes. Molecular dynamics (MD) has become a particularly important tool in drug design and discovery. From classical MD methods to more sophisticated hybrid classical/quantum mechanical (QM) approaches, MD simulations are now able to offer extraordinary insights into ligand-receptor interactions. In this review, we discuss how the applications of MD approaches are significantly transforming current drug discovery and development efforts. Copyright © 2016 Elsevier Ltd. All rights reserved.

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…

[From discovery to innovation: the example of hypereosinophilic syndrome].

PubMed

Goldman, M

2007-01-01

Biomedical research is extremely productive so that each day new discoveries reveal novel (mechanisms and) molecular pathways of diseases. However, the number of innovative therapies approved each year by regulatory authorities is decreasing. The causes of this "innovation breakdown" are multiple and should be explored both in academic institutions and in the industrial world. New initiatives are underway in the Walloon Region to improve this situation, such as the setting up of the BioWin Health Cluster gathering pharmaceutical and biotechnology enterprises and university laboratories. This new vision of the partnership between academia and the private sector should be based on strong fundamental research activities. We illustrate this concept by discussing recent advances in the diagnosis and treatment of the hypereosinophilic syndrome.

The Discovery of Reverse Transcriptase.

PubMed

Coffin, John M; Fan, Hung

2016-09-29

In 1970 the independent and simultaneous discovery of reverse transcriptase in retroviruses (then RNA tumor viruses) by David Baltimore and Howard Temin revolutionized molecular biology and laid the foundations for retrovirology and cancer biology. In this historical review we describe the formulation of the controversial provirus hypothesis by Temin, which ultimately was proven by his discovery of reverse transcriptase in Rous sarcoma virus virions. Baltimore arrived at the same discovery through his studies on replication of RNA-containing viruses, starting with poliovirus and then moving to vesicular stomatitis virus, where he discovered a virion RNA polymerase. Subsequent studies of reverse transcriptase led to the elucidation of the mechanism of retrovirus replication, the discovery of oncogenes, the advent of molecular cloning, the search for human cancer viruses, and the discovery and treatment of HIV/AIDS.

The role of extreme events in evolution

NASA Astrophysics Data System (ADS)

Combes, Claude

2008-09-01

Evolutionists have often had a marked tendency to think that, in the course of time, planetary events were not very different from those occurring during a human life. However, when a 'non-human' timescale is used, the history of our planet appears profoundly and frequently disturbed by extreme events. These events, even not always instantaneous, impose - because of their amplitude - a severe sorting, not between individuals of a species, but between species, or even between phyla. In the face of an extreme event, intraspecific diversity counts little: it is the interspecific diversity that makes the difference. As shown by mass extinctions, extreme events open ecological niches and redistribute the cards of life, giving survivors opportunities to radiate. The capacity to cope with extreme ecological conditions favours certain species in ecosystems, not certain individuals in populations. This is not a macroevolutionary process in terms of acquiring new adaptations, but a macroevolutionary process in terms of sorting entire sections of life. The most important is perhaps that the current 'mediatisation' of a limited number of mass extinctions dissimulates less important extinctions caused by less extreme and more localized events that were possibly responsible for many changes in the composition and structure of communities throughout the evolution. The term of 'pre-adaptation' has been neglected, because it gives an impression of finalism, but it expresses well that, when an unexpected event occurs, a particular species has or has not the 'right genes' to continue to sustain viable populations. The role of extreme events in modifying the course of evolution should not be underestimated.

The extreme melt across the Greenland ice sheet in 2012

NASA Astrophysics Data System (ADS)

Nghiem, S. V.; Hall, D. K.; Mote, T. L.; Tedesco, M.; Albert, M. R.; Keegan, K.; Shuman, C. A.; DiGirolamo, N. E.; Neumann, G.

2012-10-01

The discovery of the 2012 extreme melt event across almost the entire surface of the Greenland ice sheet is presented. Data from three different satellite sensors - including the Oceansat-2 scatterometer, the Moderate-resolution Imaging Spectroradiometer, and the Special Sensor Microwave Imager/Sounder - are combined to obtain composite melt maps, representing the most complete melt conditions detectable across the ice sheet. Satellite observations reveal that melt occurred at or near the surface of the Greenland ice sheet across 98.6% of its entire extent on 12 July 2012, including the usually cold polar areas at high altitudes like Summit in the dry snow facies of the ice sheet. This melt event coincided with an anomalous ridge of warm air that became stagnant over Greenland. As seen in melt occurrences from multiple ice core records at Summit reported in the published literature, such a melt event is rare with the last significant one occurring in 1889 and the next previous one around seven centuries earlier in the Medieval Warm Period. Given its rarity, the 2012 extreme melt across Greenland provides an exceptional opportunity for new studies in broad interdisciplinary geophysical research.

DISCOVERY OF RR LYRAE STARS IN THE NUCLEAR BULGE OF THE MILKY WAY

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

Minniti, Dante; Ramos, Rodrigo Contreras; Zoccali, Manuela

Galactic nuclei, such as that of the Milky Way, are extreme regions with high stellar densities, and in most cases, the hosts of a supermassive black hole. One of the scenarios proposed for the formation of the Galactic nucleus is merging of primordial globular clusters. An implication of this model is that this region should host stars that are characteristically found in old Milky Way globular clusters. RR Lyrae stars are primary distance indicators, well known representatives of old and metal-poor stellar populations, and therefore are regularly found in globular clusters. Here we report the discovery of a dozen RRmore » Lyrae type ab stars in the vicinity of the Galactic center, i.e., in the so-called nuclear stellar bulge of the Milky Way. This discovery provides the first direct observational evidence that the Galactic nuclear stellar bulge contains ancient stars (>10 Gyr old). Based on this we conclude that merging globular clusters likely contributed to the build-up of the high stellar density in the nuclear stellar bulge of the Milky Way.« less

Cancer epigenetics drug discovery and development: the challenge of hitting the mark

PubMed Central

Campbell, Robert M.; Tummino, Peter J.

2014-01-01

Over the past several years, there has been rapidly expanding evidence of epigenetic dysregulation in cancer, in which histone and DNA modification play a critical role in tumor growth and survival. These findings have gained the attention of the drug discovery and development community, and offer the potential for a second generation of cancer epigenetic agents for patients following the approved “first generation” of DNA methylation (e.g., Dacogen, Vidaza) and broad-spectrum HDAC inhibitors (e.g., Vorinostat, Romidepsin). This Review provides an analysis of prospects for discovery and development of novel cancer agents that target epigenetic proteins. We will examine key examples of epigenetic dysregulation in tumors as well as challenges to epigenetic drug discovery with emerging biology and novel classes of drug targets. We will also highlight recent successes in cancer epigenetics drug discovery and consider important factors for clinical success in this burgeoning area. PMID:24382391

Academic drug discovery: current status and prospects.

PubMed

Everett, Jeremy R

2015-01-01

The contraction in pharmaceutical drug discovery operations in the past decade has been counter-balanced by a significant rise in the number of academic drug discovery groups. In addition, pharmaceutical companies that used to operate in completely independent, vertically integrated operations for drug discovery, are now collaborating more with each other, and with academic groups. We are in a new era of drug discovery. This review provides an overview of the current status of academic drug discovery groups, their achievements and the challenges they face, together with perspectives on ways to achieve improved outcomes. Academic groups have made important contributions to drug discovery, from its earliest days and continue to do so today. However, modern drug discovery and development is exceedingly complex, and has high failure rates, principally because human biology is complex and poorly understood. Academic drug discovery groups need to play to their strengths and not just copy what has gone before. However, there are lessons to be learnt from the experiences of the industrial drug discoverers and four areas are highlighted for attention: i) increased validation of targets; ii) elimination of false hits from high throughput screening (HTS); iii) increasing the quality of molecular probes; and iv) investing in a high-quality informatics infrastructure.

Viral pathogen discovery

PubMed Central

Chiu, Charles Y

2015-01-01

Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease. PMID:23725672

Discovery prepares to land after successful mission STS-95

NASA Technical Reports Server (NTRS)

1998-01-01

Orbiter Discovery prepares to land on runway 33 at the Shuttle Landing Facility. Discovery returns to Earth with its crew of seven after successfully completing mission STS-95, lasting nearly nine days and 3.6 million miles. The crew members are Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Mission Specialist Scott E. Parazynski, Mission Specialist Stephen K. Robinson, Payload Specialist John H. Glenn Jr., senator from Ohio, Mission Specialist Pedro Duque, with the European Space Agency (ESA), and Payload Specialist Chiaki Mukai, with the National Space Development Agency of Japan (NASDA). The mission included research payloads such as the Spartan solar- observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

Understanding the importance of transient resonances in extreme mass ratio inspirals

NASA Astrophysics Data System (ADS)

Berry, C. P. L.; Cole, R. H.; Cañizares, P.; Gair, J. R.

2017-05-01

Extreme mass ratio inspirals (EMRIs) occur when a compact object orbits a much larger one, like a solar-mass black hole around a supermassive black hole. The orbit has 3 frequencies which evolve through the inspiral. If the orbital radial frequency and polar frequency become commensurate, the system passes through a transient resonance. Evolving through resonance causes a jump in the evolution of the orbital parameters. We study these jumps and their impact on EMRI gravitational-wave detection. Jumps are smaller for lower eccentricity orbits; since most EMRIs have small eccentricities when passing through resonances, we expect that the impact on detection will be small. Neglecting the effects of transient resonances leads to a loss of ∼ 4% of detectable signals for an astrophysically motivated population of EMRIs.

The Impact of Students' Exploration Strategies on Discovery Learning Using Computer-Based Simulations

ERIC Educational Resources Information Center

Dalgarno, Barney; Kennedy, Gregor; Bennett, Sue

2014-01-01

Discovery-based learning designs incorporating active exploration are common within instructional software. However, researchers have highlighted empirical evidence showing that "pure" discovery learning is of limited value and strategies which reduce complexity and provide guidance to learners are important if potential learning…

HE 0430-2457: a post-merger extremely low-mass pre-white dwarf in a wide binary posing as an extreme horizontal branch star

NASA Astrophysics Data System (ADS)

Vos, Joris; Zorotovic, Monica; Vučković, Maja; Schreiber, Matthias R.; Østensen, Roy

2018-06-01

We report the discovery of HE 0430-2457, the first extremely low-mass pre-white dwarf (ELM pre-WD) in a long period binary (P = 771 ± 3 d). The spectroscopic parameters of the primary are determined to be Teff = 26 200 ± 1500 K and log g = 5.40 ± 0.35, placing it in the region occupied by core He-burning hot subdwarf B stars. By comparing the spectroscopic parameters of the K-type companion to stellar models, and using the mass ratio, the mass of the hot primary is determined to be 0.23 M⊙. Given that this is too low for core He-burning, the primary in HE 0430-2457 is not an extreme horizontal branch (EHB) star but a pre-WD of the ELM type. As the lifetime of ELM pre-WDs in this region of the Hertzsprung Russel diagram populated by EHBs is thought to be very short, they are not considered to be part of the observed EHBs. However, the discovery of this system indicates that the percentage of ELM pre-WDs in the observed EHB population might be higher than previously thought. Binary evolution models indicate that HE 0430-2457 is likely formed by a merger of the inner binary in a hierarchical triple system.

A Simultaneous Discovery: The Case of Johannes Stark and Antonino Lo Surdo

NASA Astrophysics Data System (ADS)

Leone, Matteo; Paoletti, Alessandro; Robotti, Nadia

2004-09-01

In 1913 the German physicist Johannes Stark (1874 1957) and the Italian physicist Antonino Lo Surdo (1880 1949)discovered virtually simultaneously and independently that hydrogen spectral lines are split into components by an external electric field. Both of their discoveries ensued from studies on the same phenomenon, the Doppler effect in canal rays, but they arose in different theoretical contexts. Stark had been working within the context of the emerging quantum theory, following a research program aimed at studying the effect of an electric field on spectral lines. Lo Surdo had been working within the context of the classical theory, and his was an accidental discovery. Both discoveries, however, played important roles in the history of physics: Stark’s discovery contributed to the establishment of both the old and the new quantum theories; Lo Surdo’s discovery led Antonio Garbasso (1871 1933)to introduce research on the quantum theory into Italian physics. Ironically, soon after their discoveries, both Stark and Lo Surdo rejected developments in modern physics and allied themselves with the political and racial programs of Hitler and Mussolini.

Payload canister for Discovery is lifted in place for transfer

NASA Technical Reports Server (NTRS)

1998-01-01

At left, the payload canister for Space Shuttle Discovery is lifted from its canister movement vehicle to the top of the Rotating Service Structure on Launch Pad 39-B. Discovery (right), sitting atop the Mobile Launch Platform and next to the Fixed Service Structure (FSS), is scheduled for launch on Oct. 29, 1998, for the STS-95 mission. That mission includes the International Extreme Ultraviolet Hitchhiker (IEH-3), the Hubble Space Telescope Orbital Systems Test Platform, the Spartan solar- observing deployable spacecraft, and the SPACEHAB single module with experiments on space flight and the aging process. At the top of the FSS can be seen the 80-foot lightning mast . The 4- foot-high lightning rod on top helps prevent lightning current from passing directly through the Space Shuttle and the structures on the pad.

Genomics and transcriptomics in drug discovery.

PubMed

Dopazo, Joaquin

2014-02-01

The popularization of genomic high-throughput technologies is causing a revolution in biomedical research and, particularly, is transforming the field of drug discovery. Systems biology offers a framework to understand the extensive human genetic heterogeneity revealed by genomic sequencing in the context of the network of functional, regulatory and physical protein-drug interactions. Thus, approaches to find biomarkers and therapeutic targets will have to take into account the complex system nature of the relationships of the proteins with the disease. Pharmaceutical companies will have to reorient their drug discovery strategies considering the human genetic heterogeneity. Consequently, modeling and computational data analysis will have an increasingly important role in drug discovery. Copyright © 2013 Elsevier Ltd. All rights reserved.

Discovery of the Closest Hot Subdwarf Binary with White Dwarf Companion

NASA Astrophysics Data System (ADS)

Geier, S.; Marsh, T. R.; Dunlap, B. H.; Barlow, B. N.; Schaffenroth, V.; Ziegerer, E.; Heber, U.; Kupfer, T.; Maxted, P. F. L.; Miszalski, B.; Shporer, A.; Telting, J. H.; Ostensen, R. H.; O'Toole, S. J.; Gänsicke, B. T.; Napiwotzki, R.

2013-01-01

We report the discovery of an extremely close, eclipsing binary system. A white dwarf is orbited by a core He-burning compact hot subdwarf star with a period as short as ≃ 0.04987 d making this system the most compact hot subdwarf binary discovered so far. The subdwarf will start to transfer helium-rich material on short timescales of less than 50 Myr. The ignition of He-burning at the surface may trigger carbon-burning in the core although the WD is less massive than the Chandrasekhar limit (> 0.74 M⊙) making this binary a possible progenitor candidate for a supernova type Ia event.

Polygenic determinants in extremes of high-density lipoprotein cholesterol.

PubMed

Dron, Jacqueline S; Wang, Jian; Low-Kam, Cécile; Khetarpal, Sumeet A; Robinson, John F; McIntyre, Adam D; Ban, Matthew R; Cao, Henian; Rhainds, David; Dubé, Marie-Pierre; Rader, Daniel J; Lettre, Guillaume; Tardif, Jean-Claude; Hegele, Robert A

2017-11-01

HDL cholesterol (HDL-C) remains a superior biochemical predictor of CVD risk, but its genetic basis is incompletely defined. In patients with extreme HDL-C concentrations, we concurrently evaluated the contributions of multiple large- and small-effect genetic variants. In a discovery cohort of 255 unrelated lipid clinic patients with extreme HDL-C levels, we used a targeted next-generation sequencing panel to evaluate rare variants in known HDL metabolism genes, simultaneously with common variants bundled into a polygenic trait score. Two additional cohorts were used for validation and included 1,746 individuals from the Montréal Heart Institute Biobank and 1,048 individuals from the University of Pennsylvania. Findings were consistent between cohorts: we found rare heterozygous large-effect variants in 18.7% and 10.9% of low- and high-HDL-C patients, respectively. We also found common variant accumulation, indicated by extreme polygenic trait scores, in an additional 12.8% and 19.3% of overall cases of low- and high-HDL-C extremes, respectively. Thus, the genetic basis of extreme HDL-C concentrations encountered clinically is frequently polygenic, with contributions from both rare large-effect and common small-effect variants. Multiple types of genetic variants should be considered as contributing factors in patients with extreme dyslipidemia. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Polygenic determinants in extremes of high-density lipoprotein cholesterol[S

PubMed Central

Dron, Jacqueline S.; Wang, Jian; Low-Kam, Cécile; Khetarpal, Sumeet A.; Robinson, John F.; McIntyre, Adam D.; Ban, Matthew R.; Cao, Henian; Rhainds, David; Dubé, Marie-Pierre; Rader, Daniel J.; Lettre, Guillaume; Tardif, Jean-Claude

2017-01-01

HDL cholesterol (HDL-C) remains a superior biochemical predictor of CVD risk, but its genetic basis is incompletely defined. In patients with extreme HDL-C concentrations, we concurrently evaluated the contributions of multiple large- and small-effect genetic variants. In a discovery cohort of 255 unrelated lipid clinic patients with extreme HDL-C levels, we used a targeted next-generation sequencing panel to evaluate rare variants in known HDL metabolism genes, simultaneously with common variants bundled into a polygenic trait score. Two additional cohorts were used for validation and included 1,746 individuals from the Montréal Heart Institute Biobank and 1,048 individuals from the University of Pennsylvania. Findings were consistent between cohorts: we found rare heterozygous large-effect variants in 18.7% and 10.9% of low- and high-HDL-C patients, respectively. We also found common variant accumulation, indicated by extreme polygenic trait scores, in an additional 12.8% and 19.3% of overall cases of low- and high-HDL-C extremes, respectively. Thus, the genetic basis of extreme HDL-C concentrations encountered clinically is frequently polygenic, with contributions from both rare large-effect and common small-effect variants. Multiple types of genetic variants should be considered as contributing factors in patients with extreme dyslipidemia. PMID:28870971

Moving in extreme environments: what's extreme and who decides?

PubMed

Cotter, James David; Tipton, Michael J

2014-01-01

Humans work, rest and play in immensely varied extreme environments. The term 'extreme' typically refers to insufficiency or excess of one or more stressors, such as thermal energy or gravity. Individuals' behavioural and physiological capacity to endure and enjoy such environments varies immensely. Adverse effects of acute exposure to these environments are readily identifiable (e.g. heat stroke or bone fracture), whereas adverse effects of chronic exposure (e.g. stress fractures or osteoporosis) may be as important but much less discernable. Modern societies have increasingly sought to protect people from such stressors and, in that way, minimise their adverse effects. Regulations are thus established, and advice is provided on what is 'acceptable' exposure. Examples include work/rest cycles in the heat, hydration regimes, rates of ascent to and duration of stay at altitude and diving depth. While usually valuable and well intentioned, it is important to realise the breadth and importance of limitations associated with such guidelines. Regulations and advisories leave less room for self-determination, learning and perhaps adaptation. Regulations based on stress (e.g. work/rest cycles relative to WBGT) are more practical but less direct than those based on strain (e.g. core temperature), but even the latter can be substantively limited (e.g. by lack of criterion validation and allowance for behavioural regulation in the research on which they are based). Extreme Physiology & Medicine is publishing a series of reviews aimed at critically examining the issues involved with self- versus regulation-controlled human movement acutely and chronically in extreme environments. These papers, arising from a research symposium in 2013, are about the impact of people engaging in such environments and the effect of rules and guidelines on their safety, enjoyment, autonomy and productivity. The reviews will cover occupational heat stress, sporting heat stress, hydration, diving

19 CFR 210.61 - Discovery and compulsory process.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery and compulsory process. 210.61 Section 210.61 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Temporary Relief § 210.61 Discovery and compulsory...

19 CFR 210.27 - General provisions governing discovery.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false General provisions governing discovery. 210.27 Section 210.27 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Discovery and Compulsory Process § 210.27 General...

Ecological Guild Evolution and the Discovery of the World's Smallest Vertebrate

PubMed Central

Rittmeyer, Eric N.; Allison, Allen; Gründler, Michael C.; Thompson, Derrick K.; Austin, Christopher C.

2012-01-01

Living vertebrates vary drastically in body size, yet few taxa reach the extremely minute size of some frogs and teleost fish. Here we describe two new species of diminutive terrestrial frogs from the megadiverse hotspot island of New Guinea, one of which represents the smallest known vertebrate species, attaining an average body size of only 7.7 mm. Both new species are members of the recently described genus Paedophryne, the four species of which are all among the ten smallest known frog species, making Paedophryne the most diminutive genus of anurans. This discovery highlights intriguing ecological similarities among the numerous independent origins of diminutive anurans, suggesting that minute frogs are not mere oddities, but represent a previously unrecognized ecological guild. PMID:22253785

Early prediction of extreme stratospheric polar vortex states based on causal precursors

NASA Astrophysics Data System (ADS)

Kretschmer, Marlene; Runge, Jakob; Coumou, Dim

2017-08-01

Variability in the stratospheric polar vortex (SPV) can influence the tropospheric circulation and thereby winter weather. Early predictions of extreme SPV states are thus important to improve forecasts of winter weather including cold spells. However, dynamical models are usually restricted in lead time because they poorly capture low-frequency processes. Empirical models often suffer from overfitting problems as the relevant physical processes and time lags are often not well understood. Here we introduce a novel empirical prediction method by uniting a response-guided community detection scheme with a causal discovery algorithm. This way, we objectively identify causal precursors of the SPV at subseasonal lead times and find them to be in good agreement with known physical drivers. A linear regression prediction model based on the causal precursors can explain most SPV variability (r2 = 0.58), and our scheme correctly predicts 58% (46%) of extremely weak SPV states for lead times of 1-15 (16-30) days with false-alarm rates of only approximately 5%. Our method can be applied to any variable relevant for (sub)seasonal weather forecasts and could thus help improving long-lead predictions.

The Greatest Mathematical Discovery?

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

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 aboutmore » 500 CE.« less

Solution NMR Spectroscopy in Target-Based Drug Discovery.

PubMed

Li, Yan; Kang, Congbao

2017-08-23

Solution NMR spectroscopy is a powerful tool to study protein structures and dynamics under physiological conditions. This technique is particularly useful in target-based drug discovery projects as it provides protein-ligand binding information in solution. Accumulated studies have shown that NMR will play more and more important roles in multiple steps of the drug discovery process. In a fragment-based drug discovery process, ligand-observed and protein-observed NMR spectroscopy can be applied to screen fragments with low binding affinities. The screened fragments can be further optimized into drug-like molecules. In combination with other biophysical techniques, NMR will guide structure-based drug discovery. In this review, we describe the possible roles of NMR spectroscopy in drug discovery. We also illustrate the challenges encountered in the drug discovery process. We include several examples demonstrating the roles of NMR in target-based drug discoveries such as hit identification, ranking ligand binding affinities, and mapping the ligand binding site. We also speculate the possible roles of NMR in target engagement based on recent processes in in-cell NMR spectroscopy.

Natural products discovery from micro-organisms in the post-genome era.

PubMed

Ikeda, Haruo

2017-01-01

With the decision to award the Nobel Prize in Physiology or Medicine to Drs. S. Ōmura, W.C. Campbell, and Y. Tu, the importance and usefulness of natural drug discovery and development have been revalidated. Since the end of the twentieth century, many genome analyses of organisms have been conducted, and accordingly, numerous microbial genomes have been decoded. In particular, genomic studies of actinomycetes, micro-organisms that readily produce natural products, led to the discovery of biosynthetic gene clusters responsible for producing natural products. New explorations for natural products through a comprehensive approach combining genomic information with conventional methods show great promise for the discovery of new natural products and even systematic generation of unnaturally occurring compounds.

"Drug" Discovery with the Help of Organic Chemistry.

PubMed

Itoh, Yukihiro; Suzuki, Takayoshi

2017-01-01

The first step in "drug" discovery is to find compounds binding to a potential drug target. In modern medicinal chemistry, the screening of a chemical library, structure-based drug design, and ligand-based drug design, or a combination of these methods, are generally used for identifying the desired compounds. However, they do not necessarily lead to success and there is no infallible method for drug discovery. Therefore, it is important to explore medicinal chemistry based on not only the conventional methods but also new ideas. So far, we have found various compounds as drug candidates. In these studies, some strategies based on organic chemistry have allowed us to find drug candidates, through 1) construction of a focused library using organic reactions and 2) rational design of enzyme inhibitors based on chemical reactions catalyzed by the target enzyme. Medicinal chemistry based on organic chemical reactions could be expected to supplement the conventional methods. In this review, we present drug discovery with the help of organic chemistry showing examples of our explorative studies on histone deacetylase inhibitors and lysine-specific demethylase 1 inhibitors.

Discovery and bio-optimization of human antibody therapeutics using the XenoMouse® transgenic mouse platform.

PubMed

Foltz, Ian N; Gunasekaran, Kannan; King, Chadwick T

2016-03-01

Since the late 1990s, the use of transgenic animal platforms has transformed the discovery of fully human therapeutic monoclonal antibodies. The first approved therapy derived from a transgenic platform--the epidermal growth factor receptor antagonist panitumumab to treat advanced colorectal cancer--was developed using XenoMouse(®) technology. Since its approval in 2006, the science of discovering and developing therapeutic monoclonal antibodies derived from the XenoMouse(®) platform has advanced considerably. The emerging array of antibody therapeutics developed using transgenic technologies is expected to include antibodies and antibody fragments with novel mechanisms of action and extreme potencies. In addition to these impressive functional properties, these antibodies will be designed to have superior biophysical properties that enable highly efficient large-scale manufacturing methods. Achieving these new heights in antibody drug discovery will ultimately bring better medicines to patients. Here, we review best practices for the discovery and bio-optimization of monoclonal antibodies that fit functional design goals and meet high manufacturing standards. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tryggvason and Robinson examine Discovery after landing

NASA Technical Reports Server (NTRS)

1997-01-01

STS-85 Payload Specialist and Canadian Space Agency astronaut Bjarni V. Tryggvason (left) and Mission Specialist Stephen K. Robinson examine the Space Shuttle orbiter Discovery after the space plane landed on Runway 33 at KSCs Shuttle Landing Facility Aug. 19 to complete the 11-day, 20-hour and 27-minute-long STS-85 mission. Also on board were Commander Curtis L. Brown, Jr., Pilot Kent V. Rominger, Payload Commander N. Jan Davis and Mission Specialist Robert L. Curbeam, Jr. During the 86th Space Shuttle mission, the crew deployed the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere-Shuttle Pallet Satellite-2 (CRISTA-SPAS-2) free-flyer to conduct research on the Earths middle atmosphere, retrieving it on flight day 9. The crew also conducted investigations with the Manipulator Flight Demonstration (MFD), Technology Applications and Science-1 (TAS- 1) and International Extreme Ultraviolet Hitchhiker-2 (IEH-2) experiments. This was the 39th landing at KSC in the history of the Space Shuttle program and the 11th touchdown for Discovery at the space center.

DISCOVERY OF PULSATIONS, INCLUDING POSSIBLE PRESSURE MODES, IN TWO NEW EXTREMELY LOW MASS, He-CORE WHITE DWARFS

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

Hermes, J. J.; Montgomery, M. H.; Winget, D. E.

2013-03-10

We report the discovery of the second and third pulsating extremely low mass (ELM) white dwarfs (WDs), SDSS J111215.82+111745.0 (hereafter J1112) and SDSS J151826.68+065813.2 (hereafter J1518). Both have masses < 0.25 M{sub Sun} and effective temperatures below 10, 000 K, establishing these putatively He-core WDs as a cooler class of pulsating hydrogen-atmosphere WDs (DAVs, or ZZ Ceti stars). The short-period pulsations evidenced in the light curve of J1112 may also represent the first observation of acoustic (p-mode) pulsations in any WD, which provide an exciting opportunity to probe this WD in a complimentary way compared to the long-period g-modes thatmore » are also present. J1112 is a T{sub eff} =9590 {+-} 140 K and log g =6.36 {+-} 0.06 WD. The star displays sinusoidal variability at five distinct periodicities between 1792 and 2855 s. In this star, we also see short-period variability, strongest at 134.3 s, well short of the expected g-modes for such a low-mass WD. The other new pulsating WD, J1518, is a T{sub eff} =9900 {+-} 140 K and log g =6.80 {+-} 0.05 WD. The light curve of J1518 is highly non-sinusoidal, with at least seven significant periods between 1335 and 3848 s. Consistent with the expectation that ELM WDs must be formed in binaries, these two new pulsating He-core WDs, in addition to the prototype SDSS J184037.78+642312.3, have close companions. However, the observed variability is inconsistent with tidally induced pulsations and is so far best explained by the same hydrogen partial-ionization driving mechanism at work in classic C/O-core ZZ Ceti stars.« less

Mainstream Media and Social Media Reactions to the Discovery of Extraterrestrial Life

NASA Astrophysics Data System (ADS)

Jones, Morris

The rise of online social media (such as Facebook and Twitter) has overturned traditional top-down and stovepiped channels for mass communications. As social media have risen, traditional media sources have been steadily crippled by economic problems, resulting in a loss of capabilities and credibility. Information can propagate rapidly without the inclusion of traditional editorial checks and controls. Mass communications strategies for any type of major announcement must account for this new media landscape. Scientists announcing the discovery of extraterrestrial life will trigger a multifaceted and unpredictable percolation of the story through the public sphere. They will also potentially struggle with misinformation, rumours and hoaxes. The interplay of official announcements with the discussions of an extraterrestrial discovery on social media has parallels with traditional theories of mass communications. A wide spectrum of different messages is likely to be received by different segments of the community, based on their usage patterns of various media and online communications. The presentation and interpretation of a discovery will be hotly debated and contested within online media environments. In extreme cases, this could lead to "editorial wars" on collaborative media projects as well as cyber-attacks on certain online services and individuals. It is unlikely that a clear and coherent message can be propagated to a near-universal level. This has the potential to contribute to inappropriate reactions in some sectors of the community. Preventing unnecessary panic will be a priority. In turn, the monitoring of online and social media will provide a useful tool for assessing public reactions to a discovery of extraterrestrial life. This will help to calibrate public communications strategies following in the wake of an initial announcement.

STS-85 Mission Specialist Robinson prepares to enter Discovery

NASA Technical Reports Server (NTRS)

1997-01-01

STS-85 Mission Specialist Stephen K. Robinson prepares to enter the Space Shuttle orbiter Discovery at Launch Complex 39A just prior to launch, scheduled for 10:41 a.m. EDT. The primary payload on this mission is the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere-Shuttle Pallet Satellite-2 (CRISTA-SPAS-2) free-flyer. The CRISTA-SPAS-2 will be deployed on flight day 1 to study trace gases in the Earths atmosphere as a part of NASAs Mission to Planet Earth program. Also aboard the free-flying research platform will be the Middle Atmosphere High Resolution Spectrograph Instrument (MAHRSI). Other payloads on the 11-day mission include the Manipulator Flight Demonstration (MFD), a Japanese Space Agency-sponsored experiment. Also in Discoverys payload bay are the Technology Applications and Science-1 (TAS-1) and International Extreme Ultraviolet Hitchhiker-2 (IEH-2) experiments.

Geospatial Crypto Reconnaissance: A Campus Self-Discovery Game

ERIC Educational Resources Information Center

Lallie, Harjinder Singh

2015-01-01

Campus discovery is an important feature of a university student induction process. Approaches towards campus discovery differ from course to course and can comprise guided tours that are often lengthy and uninspiring, or self-guided tours that run the risk of students failing to complete them. This paper describes a campus self-discovery…

The promise of disease gene discovery in South Asia

PubMed Central

Nakatsuka, Nathan; Moorjani, Priya; Rai, Niraj; Sarkar, Biswanath; Tandon, Arti; Patterson, Nick; Bhavani, Gandham SriLakshmi; Girisha, Katta Mohan; Mustak, Mohammed S; Srinivasan, Sudha; Kaushik, Amit; Vahab, Saadi Abdul; Jagadeesh, Sujatha M.; Satyamoorthy, Kapaettu; Singh, Lalji; Reich, David; Thangaraj, Kumarasamy

2017-01-01

The more than 1.5 billion people who live in South Asia are correctly viewed not as a single large population, but as many small endogamous groups. We assembled genome-wide data from over 2,800 individuals from over 260 distinct South Asian groups. We identify 81 unique groups, of which 14 have estimated census sizes of more than a million, that descend from founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events. We identify multiple examples of recessive diseases in South Asia that are the result of such founder events. This study highlights an under-appreciated opportunity for reducing disease burden among South Asians through the discovery of and testing for recessive disease genes. PMID:28714977

Overcoming the challenges of drug discovery for neglected tropical diseases: the A·WOL experience.

PubMed

Johnston, Kelly L; Ford, Louise; Taylor, Mark J

2014-03-01

Neglected tropical diseases (NTDs) are a group of 17 diseases that typically affect poor people in tropical countries. Each has been neglected for decades in terms of funding, research, and policy, but the recent grouping of them into one unit, which can be targeted using integrated control measures, together with increased advocacy has helped to place them on the global health agenda. The World Health Organization has set ambitious goals to control or eliminate 10 NTDs by 2020 and launched a roadmap in January 2012 to guide this global plan. The result of the launch meeting, which brought together representatives from the pharmaceutical industry, donors, and politicians, was the London Declaration: a series of commitments to provide more drugs, research, and funds to achieve the 2020 goals. Drug discovery and development for these diseases are extremely challenging, and this article highlights these challenges in the context of the London Declaration, before focusing on an example of a drug discovery and development program for the NTDs onchocerciasis and lymphatic filariasis (the anti-Wolbachia consortium, A·WOL).

Spatial extremes modeling applied to extreme precipitation data in the state of Paraná

NASA Astrophysics Data System (ADS)

Olinda, R. A.; Blanchet, J.; dos Santos, C. A. C.; Ozaki, V. A.; Ribeiro, P. J., Jr.

2014-11-01

Most of the mathematical models developed for rare events are based on probabilistic models for extremes. Although the tools for statistical modeling of univariate and multivariate extremes are well developed, the extension of these tools to model spatial extremes includes an area of very active research nowadays. A natural approach to such a modeling is the theory of extreme spatial and the max-stable process, characterized by the extension of infinite dimensions of multivariate extreme value theory, and making it possible then to incorporate the existing correlation functions in geostatistics and therefore verify the extremal dependence by means of the extreme coefficient and the Madogram. This work describes the application of such processes in modeling the spatial maximum dependence of maximum monthly rainfall from the state of Paraná, based on historical series observed in weather stations. The proposed models consider the Euclidean space and a transformation referred to as space weather, which may explain the presence of directional effects resulting from synoptic weather patterns. This method is based on the theorem proposed for de Haan and on the models of Smith and Schlather. The isotropic and anisotropic behavior of these models is also verified via Monte Carlo simulation. Estimates are made through pairwise likelihood maximum and the models are compared using the Takeuchi Information Criterion. By modeling the dependence of spatial maxima, applied to maximum monthly rainfall data from the state of Paraná, it was possible to identify directional effects resulting from meteorological phenomena, which, in turn, are important for proper management of risks and environmental disasters in countries with its economy heavily dependent on agribusiness.

The Significance of Acid/Base Properties in Drug Discovery

PubMed Central

Manallack, David T.; Prankerd, Richard J.; Yuriev, Elizabeth; Oprea, Tudor I.; Chalmers, David K.

2013-01-01

While drug discovery scientists take heed of various guidelines concerning drug-like character, the influence of acid/base properties often remains under-scrutinised. Ionisation constants (pKa values) are fundamental to the variability of the biopharmaceutical characteristics of drugs and to underlying parameters such as logD and solubility. pKa values affect physicochemical properties such as aqueous solubility, which in turn influences drug formulation approaches. More importantly, absorption, distribution, metabolism, excretion and toxicity (ADMET) are profoundly affected by the charge state of compounds under varying pH conditions. Consideration of pKa values in conjunction with other molecular properties is of great significance and has the potential to be used to further improve the efficiency of drug discovery. Given the recent low annual output of new drugs from pharmaceutical companies, this review will provide a timely reminder of an important molecular property that influences clinical success. PMID:23099561

Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling.

PubMed

Mariman, Edwin C M; Bouwman, Freek G; Aller, Erik E J G; van Baak, Marleen A; Wang, Ping

2015-06-01

The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rate<0.05). Six novel rare deleterious missense variants were found in the genes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling. Copyright © 2015 the American Physiological Society.

A renaissance of neural networks in drug discovery.

PubMed

Baskin, Igor I; Winkler, David; Tetko, Igor V

2016-08-01

Neural networks are becoming a very popular method for solving machine learning and artificial intelligence problems. The variety of neural network types and their application to drug discovery requires expert knowledge to choose the most appropriate approach. In this review, the authors discuss traditional and newly emerging neural network approaches to drug discovery. Their focus is on backpropagation neural networks and their variants, self-organizing maps and associated methods, and a relatively new technique, deep learning. The most important technical issues are discussed including overfitting and its prevention through regularization, ensemble and multitask modeling, model interpretation, and estimation of applicability domain. Different aspects of using neural networks in drug discovery are considered: building structure-activity models with respect to various targets; predicting drug selectivity, toxicity profiles, ADMET and physicochemical properties; characteristics of drug-delivery systems and virtual screening. Neural networks continue to grow in importance for drug discovery. Recent developments in deep learning suggests further improvements may be gained in the analysis of large chemical data sets. It's anticipated that neural networks will be more widely used in drug discovery in the future, and applied in non-traditional areas such as drug delivery systems, biologically compatible materials, and regenerative medicine.

Important science--it's all about the SPIN.

PubMed

Casadevall, Arturo; Fang, Ferric C

2009-10-01

The importance of a scientific finding can be difficult to ascertain because it requires both subjective judgment and foresight. We propose criteria, based upon whether a discovery is sizeable (S), practical (P), integrated (I), and new (N), that can be used individually or collectively to systematically assess the importance of a finding.

The prepared mind. [Serendipitous discovery of demulsifier

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

Thompson, N.E.S.

Products derived from the work of scientists with serendipity, or an imagined faculty for making fluke discoveries by looking for one thing and finding another, include the well-known examples of Teflon, penicillin, X-rays, Velcro, nylon, saccharin, and Nutrasweet. This dream of every scientist came true for the author in the discovery of a dithiocarbamate compound that could be used as a water-clarifying agent for oil fields that produce water. The new agent enables oil companies to discharge water produced in offshore drilling facilities without upsetting the clarity of the aquatic environment. The EPA limit for oil in discharged water ismore » 48 ppm. Failure to maintain this limit will result in shutdown of the platform. The alternative is to pipe the produced water to onshore facilities for treatment before discharge, which costs a good bit more. The serendipitous discovery of the dithiocarbamate compound discussed here as a unique water-clarifying agent has also led to important fundamental advances. The new agent allows producers to use existing water treatment equipment and remain in compliance with the latest limits on oil content. This compound has made it more economical to operate offshore oil and gas production facilities in the Gulf of Mexico and the North Sea.« less

Discovery Mechanisms for the Sensor Web

PubMed Central

Jirka, Simon; Bröring, Arne; Stasch, Christoph

2009-01-01

This paper addresses the discovery of sensors within the OGC Sensor Web Enablement framework. Whereas services like the OGC Web Map Service or Web Coverage Service are already well supported through catalogue services, the field of sensor networks and the according discovery mechanisms is still a challenge. The focus within this article will be on the use of existing OGC Sensor Web components for realizing a discovery solution. After discussing the requirements for a Sensor Web discovery mechanism, an approach will be presented that was developed within the EU funded project “OSIRIS”. This solution offers mechanisms to search for sensors, exploit basic semantic relationships, harvest sensor metadata and integrate sensor discovery into already existing catalogues. PMID:22574038

The discovery of the causes of leprosy: A computational analysis

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

Corruble, V.; Ganascia, J.G.

1996-12-31

The role played by the inductive inference has been studied extensively in the field of Scientific Discovery. The work presented here tackles the problem of induction in medical research. The discovery of the causes of leprosy is analyzed and simulated using computational means. An inductive algorithm is proposed, which is successful in simulating some essential steps in the progress of the understanding of the disease. It also allows us to simulate the false reasoning of previous centuries through the introduction of some medical a priori inherited form archaic medicine. Corroborating previous research, this problem illustrates the importance of the socialmore » and cultural environment on the way the inductive inference is performed in medicine.« less

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.…

Discovery and Nurturance of Giftedness in the Culturally Different.

ERIC Educational Resources Information Center

Torrance, E. Paul

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

Extremal problems for topological indices in combinatorial chemistry.

PubMed

Tichy, Robert F; Wagner, Stephan

2005-09-01

Topological indices of molecular graphs are related to several physicochemical characteristics; recently, the inverse problem for some of these indices has been studied, and it has some applications in the design of combinatorial libraries for drug discovery. It is thus very natural to study also extremal problems for these indices, i.e., finding graphs having minimal or maximal index. In this paper, these questions will be discussed for three different indices, namely the sigma-index, the c-index and the Z-index, with emphasis on the sigma-index.

Statistical characteristics of breakthrough discoveries in science using the metaphor of black and white swans

NASA Astrophysics Data System (ADS)

Zeng, Carl J.; Qi, Eric P.; Li, Simon S.; Stanley, H. Eugene; Ye, Fred Y.

2017-12-01

A publication that reports a breakthrough discovery in a particular scientific field is referred to as a ;black swan;, and the most highly-cited papers previously published in the same field ;white swans;. Important scientific progress occurs when ;white swans; meet a ;black swan;, and the citation patterns of the ;white swans; change. This metaphor combines scientific discoveries and scientometric data and suggests that breakthrough scientific discoveries are either ;black swans; or ;grey-black swans;.

Compound scale-up at the discovery-development interface.

PubMed

Nikitenko, Antonia A

2006-11-01

As a result of an economically challenging environment within the pharmaceutical industry, pharmaceutical companies and their departments must increase productivity and cut costs to stay in line with the market. Discovery-led departments such as the medicinal chemistry and lead optimization groups focus on synthesizing large varieties of compounds in minimal amounts, while the chemical development groups must then deliver a few chosen leads employing an optimized synthesis method and using multi-kilogram quantities of material. A research group at the discovery-development interface has the task of medium-scale synthesis which is important in the lead selection stage. The primary objective of this group is the initial scale-up of promising leads for extensive physicochemical and biological testing. The challenge of the interface group involves overcoming synthetic issues within the rigid, accelerated timelines.

Microbial Diversity in Extreme Marine Habitats and Their Biomolecules

PubMed Central

Poli, Annarita; Finore, Ilaria; Romano, Ida; Gioiello, Alessia; Lama, Licia; Nicolaus, Barbara

2017-01-01

Extreme marine environments have been the subject of many studies and scientific publications. For many years, these environmental niches, which are characterized by high or low temperatures, high-pressure, low pH, high salt concentrations and also two or more extreme parameters in combination, have been thought to be incompatible to any life forms. Thanks to new technologies such as metagenomics, it is now possible to detect life in most extreme environments. Starting from the discovery of deep sea hydrothermal vents up to the study of marine biodiversity, new microorganisms have been identified, and their potential uses in several applied fields have been outlined. Thermophile, halophile, alkalophile, psychrophile, piezophile and polyextremophile microorganisms have been isolated from these marine environments; they proliferate thanks to adaptation strategies involving diverse cellular metabolic mechanisms. Therefore, a vast number of new biomolecules such as enzymes, polymers and osmolytes from the inhabitant microbial community of the sea have been studied, and there is a growing interest in the potential returns of several industrial production processes concerning the pharmaceutical, medical, environmental and food fields. PMID:28509857

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. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Discovery learning with SAVI approach in geometry learning

NASA Astrophysics Data System (ADS)

Sahara, R.; Mardiyana; Saputro, D. R. S.

2018-05-01

Geometry is one branch of mathematics that an important role in learning mathematics in the schools. This research aims to find out about Discovery Learning with SAVI approach to achievement of learning geometry. This research was conducted at Junior High School in Surakarta city. Research data were obtained through test and questionnaire. Furthermore, the data was analyzed by using two-way Anova. The results showed that Discovery Learning with SAVI approach gives a positive influence on mathematics learning achievement. Discovery Learning with SAVI approach provides better mathematics learning outcomes than direct learning. In addition, students with high self-efficacy categories have better mathematics learning achievement than those with moderate and low self-efficacy categories, while student with moderate self-efficacy categories are better mathematics learning achievers than students with low self-efficacy categories. There is an interaction between Discovery Learning with SAVI approach and self-efficacy toward student's mathematics learning achievement. Therefore, Discovery Learning with SAVI approach can improve mathematics learning achievement.

On the pulse of discovery

NASA Astrophysics Data System (ADS)

2017-12-01

What started 50 years ago as a `smudge' on paper has flourished into a fundamental field of astrophysics replete with unexpected applications and exciting discoveries. To celebrate the discovery of pulsars, we look at the past, present and future of pulsar astrophysics.

Discovery of abundant hydrothermal venting on the ultraslow-spreading Gakkel ridge in the Arctic Ocean.

PubMed

Edmonds, H N; Michael, P J; Baker, E T; Connelly, D P; Snow, J E; Langmuir, C H; Dick, H J B; Mühe, R; German, C R; Graham, D W

2003-01-16

Submarine hydrothermal venting along mid-ocean ridges is an important contributor to ridge thermal structure, and the global distribution of such vents has implications for heat and mass fluxes from the Earth's crust and mantle and for the biogeography of vent-endemic organisms. Previous studies have predicted that the incidence of hydrothermal venting would be extremely low on ultraslow-spreading ridges (ridges with full spreading rates <2 cm x yr(-1)-which make up 25 per cent of the global ridge length), and that such vent systems would be hosted in ultramafic in addition to volcanic rocks. Here we present evidence for active hydrothermal venting on the Gakkel ridge, which is the slowest spreading (0.6-1.3 cm x yr(-1)) and least explored mid-ocean ridge. On the basis of water column profiles of light scattering, temperature and manganese concentration along 1,100 km of the rift valley, we identify hydrothermal plumes dispersing from at least nine to twelve discrete vent sites. Our discovery of such abundant venting, and its apparent localization near volcanic centres, requires a reassessment of the geologic conditions that control hydrothermal circulation on ultraslow-spreading ridges.

Teaching the Fundamentals of Biological Research with Primary Literature: Learning from the Discovery of the Gastric Proton Pump

ERIC Educational Resources Information Center

Zhu, Lixin

2011-01-01

For the purpose of teaching collegians the fundamentals of biological research, literature explaining the discovery of the gastric proton pump was presented in a 50-min lecture. The presentation included detailed information pertaining to the discovery process. This study was chosen because it demonstrates the importance of having a broad range of…

Copper homeostasis gene discovery in Drosophila melanogaster.

PubMed

Norgate, Melanie; Southon, Adam; Zou, Sige; Zhan, Ming; Sun, Yu; Batterham, Phil; Camakaris, James

2007-06-01

Recent studies have shown a high level of conservation between Drosophila melanogaster and mammalian copper homeostasis mechanisms. These studies have also demonstrated the efficiency with which this species can be used to characterize novel genes, at both the cellular and whole organism level. As a versatile and inexpensive model organism, Drosophila is also particularly useful for gene discovery applications and thus has the potential to be extremely useful in identifying novel copper homeostasis genes and putative disease genes. In order to assess the suitability of Drosophila for this purpose, three screening approaches have been investigated. These include an analysis of the global transcriptional response to copper in both adult flies and an embryonic cell line using DNA microarray analysis. Two mutagenesis-based screens were also utilized. Several candidate copper homeostasis genes have been identified through this work. In addition, the results of each screen were carefully analyzed to identify any factors influencing efficiency and sensitivity. These are discussed here with the aim of maximizing the efficiency of future screens and the most suitable approaches are outlined. Building on this information, there is great potential for the further use of Drosophila for copper homeostasis gene discovery.

Discovery of an extremely weak magnetic field in the white dwarf LTT 16093 = WD 2047+372

NASA Astrophysics Data System (ADS)

Landstreet, J. D.; Bagnulo, S.; Martin, A.; Valyavin, G.

2016-06-01

Context. Magnetic fields have been detected in several hundred white dwarfs, with strengths ranging from a few kG to several hundred MG. Only a few of the known fields have a mean magnetic field modulus below about 1 MG. Aims: We are searching for new examples of magnetic white dwarfs with very weak fields, and trying to model the few known examples. Our search is intended to be sensitive enough to detect fields at the few kG level. Methods: We have been surveying bright white dwarfs for very weak fields using spectropolarimeters at the Canada-France-Hawaii telescope, the William Herschel Telescope (WHT), the European Southern Observatory, and the Russian Special Astrophysical Observatory. We discuss in some detail tests of the WHT spectropolarimeter ISIS using the known magnetic strong-field Ap star HD 215441 (Babcock's star) and the long-period Ap star HD 201601 (γ Equ). Results: We report the discovery of a field with a mean field modulus of about 57 kG in the white dwarf LTT 16093 = WD 2047+372. The field is clearly detected through the Zeeman splitting of Hα seen in two separate circularly polarised spectra from two different spectropolarimeters. Zeeman circular polarisation is also detected, but only barely above the 3σ level. Conclusions: The discovery of this field is significant because it is the third weakest field ever unambiguously discovered in a white dwarf, while still being large enough that we should be able to model the field structure in some detail with future observations. Based on observations made with the William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias, and on observations obtained at the Canada-France-Hawaii Telescope (CFHT) which is operated by the National Research Council of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France, and

The in silico drug discovery toolbox: applications in lead discovery and optimization.

PubMed

Bruno, Agostino; Costantino, Gabriele; Sartori, Luca; Radi, Marco

2017-11-06

Discovery and development of a new drug is a long lasting and expensive journey that takes around 15 years from starting idea to approval and marketing of new medication. Despite the R&D expenditures have been constantly increasing in the last few years, number of new drugs introduced into market has been steadily declining. This is mainly due to preclinical and clinical safety issues, which still represent about 40% of drug discontinuation. From this point of view, it is clear that if we want to increase drug-discovery success rate and reduce costs associated with development of a new drug, a comprehensive evaluation/prediction of potential safety issues should be conducted as soon as possible during early drug discovery phase. In the present review, we will analyse the early steps of drug-discovery pipeline, describing the sequence of steps from disease selection to lead optimization and focusing on the most common in silico tools used to assess attrition risks and build a mitigation plan. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Relationships Between the Trends of Mean and Extreme Precipitation

NASA Technical Reports Server (NTRS)

Zhou, Yaping; Lau, William K.-M.

2017-01-01

This study provides a better understanding of the relationships between the trends of mean and extreme precipitation in two observed precipitation data sets: the Climate Prediction Center Unified daily precipitation data set and the Global Precipitation Climatology Program (GPCP) pentad data set. The study employs three kinds of definitions of extreme precipitation: (1) percentile, (2) standard deviation and (3) generalize extreme value (GEV) distribution analysis for extreme events based on local statistics. Relationship between trends in the mean and extreme precipitation is identified with a novel metric, i.e. area aggregated matching ratio (AAMR) computed on regional and global scales. Generally, more (less) extreme events are likely to occur in regions with a positive (negative) mean trend. The match between the mean and extreme trends deteriorates for increasingly heavy precipitation events. The AAMR is higher in regions with negative mean trends than in regions with positive mean trends, suggesting a higher likelihood of severe dry events, compared with heavy rain events in a warming climate. AAMR is found to be higher in tropics and oceans than in the extratropics and land regions, reflecting a higher degree of randomness and more important dynamical rather than thermodynamical contributions of extreme events in the latter regions.

Statistical interpretation of machine learning-based feature importance scores for biomarker discovery.

PubMed

Huynh-Thu, Vân Anh; Saeys, Yvan; Wehenkel, Louis; Geurts, Pierre

2012-07-01

Univariate statistical tests are widely used for biomarker discovery in bioinformatics. These procedures are simple, fast and their output is easily interpretable by biologists but they can only identify variables that provide a significant amount of information in isolation from the other variables. As biological processes are expected to involve complex interactions between variables, univariate methods thus potentially miss some informative biomarkers. Variable relevance scores provided by machine learning techniques, however, are potentially able to highlight multivariate interacting effects, but unlike the p-values returned by univariate tests, these relevance scores are usually not statistically interpretable. This lack of interpretability hampers the determination of a relevance threshold for extracting a feature subset from the rankings and also prevents the wide adoption of these methods by practicians. We evaluated several, existing and novel, procedures that extract relevant features from rankings derived from machine learning approaches. These procedures replace the relevance scores with measures that can be interpreted in a statistical way, such as p-values, false discovery rates, or family wise error rates, for which it is easier to determine a significance level. Experiments were performed on several artificial problems as well as on real microarray datasets. Although the methods differ in terms of computing times and the tradeoff, they achieve in terms of false positives and false negatives, some of them greatly help in the extraction of truly relevant biomarkers and should thus be of great practical interest for biologists and physicians. As a side conclusion, our experiments also clearly highlight that using model performance as a criterion for feature selection is often counter-productive. Python source codes of all tested methods, as well as the MATLAB scripts used for data simulation, can be found in the Supplementary Material.

SpS5: Accelerating the Rate of Astronomical Discovery

NASA Astrophysics Data System (ADS)

Norris, Ray P.

2010-11-01

Special Session 5 on Accelerating the Rate of Astronomical Discovery addressed a range of potential limits to progress: paradigmatic, technological, organizational, and political. It examined each issue both from modern and historical perspectives, and drew lessons to guide future progress. A number of issues were identified which may regulate the flow of discoveries, such as the balance between large strongly-focussed projects and instruments, designed to answer the most fundamental questions confronting us, and the need to maintain a creative environment with room for unorthodox thinkers and bold, high risk, projects. Also important is the need to maintain historical and cultural perspectives, and the need to engage the minds of the most brilliant young people on the planet, regardless of their background, ethnicity, gender, or geography.

Organs-on-chips at the frontiers of drug discovery

PubMed Central

Esch, Eric W.; Bahinski, Anthony; Huh, Dongeun

2016-01-01

Improving the effectiveness of preclinical predictions of human drug responses is critical to reducing costly failures in clinical trials. Recent advances in cell biology, microfabrication and microfluidics have enabled the development of microengineered models of the functional units of human organs — known as organs-on-chips — that could provide the basis for preclinical assays with greater predictive power. Here, we examine the new opportunities for the application of organ-on-chip technologies in a range of areas in preclinical drug discovery, such as target identification and validation, target-based screening, and phenotypic screening. We also discuss emerging drug discovery opportunities enabled by organs-on-chips, as well as important challenges in realizing the full potential of this technology. PMID:25792263

Upper Extremity Amputations and Prosthetics

PubMed Central

Ovadia, Steven A.; Askari, Morad

2015-01-01

Upper extremity amputations are most frequently indicated by severe traumatic injuries. The location of the injury will determine the level of amputation. Preservation of extremity length is often a goal. The amputation site will have important implications on the functional status of the patient and options for prosthetic reconstruction. Advances in amputation techniques and prosthetic reconstructions promote improved quality of life. In this article, the authors review the principles of upper extremity amputation, including techniques, amputation sites, and prosthetic reconstructions. PMID:25685104

Cardiovascular consequences of extreme prematurity: the EPICure study.

PubMed

McEniery, Carmel M; Bolton, Charlotte E; Fawke, Joseph; Hennessy, Enid; Stocks, Janet; Wilkinson, Ian B; Cockcroft, John R; Marlow, Neil

2011-07-01

The long-term consequences of extreme prematurity are becoming increasingly important, given recent improvements in neonatal intensive care. The aim of the current study was to examine the cardiovascular consequences of extreme prematurity in 11-year-olds born at or before 25 completed weeks of gestation. Age and sex-matched classmates were recruited as controls. Information concerning perinatal and maternal history was collected, and current anthropometric characteristics were measured in 219 children born extremely preterm and 153 classmates. A subset of the extremely preterm children (n = 68) and classmates (n = 90) then underwent detailed haemodynamic investigations, including measurement of supine blood pressure (BP), aortic pulse wave velocity (aPWV, a measure of aortic stiffness) and augmentation index (AIx, a measure of arterial pressure wave reflections). Seated brachial systolic and diastolic BP were not different between extremely preterm children and classmates (P = 0.3 for both), although there was a small, significant elevation in supine mean and diastolic BP in the extremely preterm children (P < 0.05 for both). Arterial pressure wave reflections were significantly elevated in the extremely preterm children (P < 0.001) and this persisted after adjusting for confounding variables. However, aortic stiffness was not different between the groups (P = 0.1). These data suggest that extreme prematurity is associated with altered arterial haemodynamics in children, not evident from the examination of brachial BP alone. Moreover, the smaller, preresistance and resistance vessels rather than large elastic arteries appear to be most affected. Children born extremely preterm may be at increased future cardiovascular risk.

A General Framework for Discovery and Classification in Astronomy

NASA Astrophysics Data System (ADS)

Dick, Steven J.

2012-09-01

An analysis of the discovery of 82 classes of astronomical objects reveals 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 nebulae), 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 detected, as in the case of gas and ice giant planets, and, infamously, Pluto as a dwarf planet. Others are inferred rather than detected, including most classes of stars.

Open Drug Discovery Toolkit (ODDT): a new open-source player in the drug discovery field.

PubMed

Wójcikowski, Maciej; Zielenkiewicz, Piotr; Siedlecki, Pawel

2015-01-01

There has been huge progress in the open cheminformatics field in both methods and software development. Unfortunately, there has been little effort to unite those methods and software into one package. We here describe the Open Drug Discovery Toolkit (ODDT), which aims to fulfill the need for comprehensive and open source drug discovery software. The Open Drug Discovery Toolkit was developed as a free and open source tool for both computer aided drug discovery (CADD) developers and researchers. ODDT reimplements many state-of-the-art methods, such as machine learning scoring functions (RF-Score and NNScore) and wraps other external software to ease the process of developing CADD pipelines. ODDT is an out-of-the-box solution designed to be easily customizable and extensible. Therefore, users are strongly encouraged to extend it and develop new methods. We here present three use cases for ODDT in common tasks in computer-aided drug discovery. Open Drug Discovery Toolkit is released on a permissive 3-clause BSD license for both academic and industrial use. ODDT's source code, additional examples and documentation are available on GitHub (https://github.com/oddt/oddt).

The Extreme Case of Magnetars

NASA Technical Reports Server (NTRS)

Kouveliotou, Chryssa

2011-01-01

Magnetars are magnetically powered rotating neutron stars with extreme magnetic fields (over 10(exp 14) Gauss). They were discovered in the X- and gamma-rays where they predominantly emit their radiation. Very few sources (roughly 18) have been found since their discovery in 1987. NASA's Fermi Gamma-ray Space Telescope was launched June 11, 2009; since then the Fermi Gamma-ray Burst Monitor (GBM) recorded emission from four magnetar sources. Two of these were brand new sources, SGR J0501+4516, discovered with Swift and extensively monitored with Swift and GBM, SGR J0418+5729, discovered with GBM and the Interplanetary Network (IPN). A third was SGR J1550-5418, a source originally classified as an Anomalous X-ray Pulsar (AXP 1E1547.0-5408), but exhibiting a very prolific outburst with over 400 events recorded in January 2009. In my talk I will give a short history of magnetars and describe how this, once relatively esoteric field, has emerged as a link between several astrophysical areas including Gamma-Ray Bursts. Finally, I will describe the exciting new results of Fermi in this field and the current status of our knowledge of the magnetar population properties and magnetic fields.

A Unique Sample of Extreme-BCG Clusters at 0.2 < z < 0.5

NASA Astrophysics Data System (ADS)

Garmire, Gordon

2017-09-01

The recently-discovered Phoenix cluster harbors the most extreme BCG in the known universe. Despite the cluster's high mass and X-ray luminosity, it was consistently identified by surveys as an isolated AGN, due to the bright central point source and the compact cool core. Armed with hindsight, we have undertaken an all-sky survey based on archival X-ray, OIR, and radio data to identify other similarly-extreme systems that were likewise missed. A pilot study demonstrated that this strategy works, leading to the discovery of a new, massive cluster at z 0.2 which was missed by previous X-ray surveys due to the presence of a bright central QSO. We propose here to observe 6 new clusters from our complete northern-sky survey, which harbor some of the most extreme central galaxies known.

Extreme halophilic archaea derive from two distinct methanogen Class II lineages.

PubMed

Aouad, Monique; Taib, Najwa; Oudart, Anne; Lecocq, Michel; Gouy, Manolo; Brochier-Armanet, Céline

2018-04-20

Phylogenetic analyses of conserved core genes have disentangled most of the ancient relationships in Archaea. However, some groups remain debated, like the DPANN, a deep-branching super-phylum composed of nanosized archaea with reduced genomes. Among these, the Nanohaloarchaea require high-salt concentrations for growth. Their discovery in 2012 was significant because they represent, together with Halobacteria (a Class belonging to Euryarchaeota), the only two described lineages of extreme halophilic archaea. The phylogenetic position of Nanohaloarchaea is highly debated, being alternatively proposed as the sister-lineage of Halobacteria or a member of the DPANN super-phylum. Pinpointing the phylogenetic position of extreme halophilic archaea is important to improve our knowledge of the deep evolutionary history of Archaea and the molecular adaptive processes and evolutionary paths that allowed their emergence. Using comparative genomic approaches, we identified 258 markers carrying a reliable phylogenetic signal. By combining strategies limiting the impact of biases on phylogenetic inference, we showed that Nanohaloarchaea and Halobacteria represent two independent lines that derived from two distinct but related methanogens Class II lineages. This implies that adaptation to high salinity emerged twice independently in Archaea and indicates that their emergence within DPANN in previous studies is likely the consequence of a tree reconstruction artifact, challenging the existence of this super-phylum. Copyright © 2018. Published by Elsevier Inc.

Changing the Scale and Efficiency of Chemical Warfare Countermeasure Discovery Using the Zebrafish

PubMed Central

Peterson, Randall T.; MacRae, Calum A.

2013-01-01

As the scope of potential chemical warfare agents grows rapidly and as the diversity of potential threat scenarios expands with non-state actors, so a need for innovative approaches to countermeasure development has emerged. In the last few years, the utility of the zebrafish as a model organism that is amenable to high-throughput screening has become apparent and this system has been applied to the unbiased discovery of chemical warfare countermeasures. This review summarizes the in vivo screening approach that has been pioneered in the countermeasure discovery arena, and highlights the successes to date as well as the potential challenges in moving the field forward. Importantly, the establishment of a zebrafish platform for countermeasure discovery would offer a rapid response system for the development of antidotes to the continuous stream of new potential chemical warfare agents. PMID:24273586

How extreme are extremes?

NASA Astrophysics Data System (ADS)

Cucchi, Marco; Petitta, Marcello; Calmanti, Sandro

2016-04-01

High temperatures have an impact on the energy balance of any living organism and on the operational capabilities of critical infrastructures. Heat-wave indicators have been mainly developed with the aim of capturing the potential impacts on specific sectors (agriculture, health, wildfires, transport, power generation and distribution). However, the ability to capture the occurrence of extreme temperature events is an essential property of a multi-hazard extreme climate indicator. Aim of this study is to develop a standardized heat-wave indicator, that can be combined with other indices in order to describe multiple hazards in a single indicator. The proposed approach can be used in order to have a quantified indicator of the strenght of a certain extreme. As a matter of fact, extremes are usually distributed in exponential or exponential-exponential functions and it is difficult to quickly asses how strong was an extreme events considering only its magnitude. The proposed approach simplify the quantitative and qualitative communication of extreme magnitude

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…

Simulating the drug discovery pipeline: a Monte Carlo approach

PubMed Central

2012-01-01

Background The early drug discovery phase in pharmaceutical research and development marks the beginning of a long, complex and costly process of bringing a new molecular entity to market. As such, it plays a critical role in helping to maintain a robust downstream clinical development pipeline. Despite its importance, however, to our knowledge there are no published in silico models to simulate the progression of discrete virtual projects through a discovery milestone system. Results Multiple variables were tested and their impact on productivity metrics examined. Simulations predict that there is an optimum number of scientists for a given drug discovery portfolio, beyond which output in the form of preclinical candidates per year will remain flat. The model further predicts that the frequency of compounds to successfully pass the candidate selection milestone as a function of time will be irregular, with projects entering preclinical development in clusters marked by periods of low apparent productivity. Conclusions The model may be useful as a tool to facilitate analysis of historical growth and achievement over time, help gauge current working group progress against future performance expectations, and provide the basis for dialogue regarding working group best practices and resource deployment strategies. PMID:23186040

Data Resources for the Computer-Guided Discovery of Bioactive Natural Products.

PubMed

Chen, Ya; de Bruyn Kops, Christina; Kirchmair, Johannes

2017-09-25

Natural products from plants, animals, marine life, fungi, bacteria, and other organisms are an important resource for modern drug discovery. Their biological relevance and structural diversity make natural products good starting points for drug design. Natural product-based drug discovery can benefit greatly from computational approaches, which are a valuable precursor or supplementary method to in vitro testing. We present an overview of 25 virtual and 31 physical natural product libraries that are useful for applications in cheminformatics, in particular virtual screening. The overview includes detailed information about each library, the extent of its structural information, and the overlap between different sources of natural products. In terms of chemical structures, there is a large overlap between freely available and commercial virtual natural product libraries. Of particular interest for drug discovery is that at least ten percent of known natural products are readily purchasable and many more natural products and derivatives are available through on-demand sourcing, extraction and synthesis services. Many of the readily purchasable natural products are of small size and hence of relevance to fragment-based drug discovery. There are also an increasing number of macrocyclic natural products and derivatives becoming available for screening.

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

Automated discovery systems and the inductivist controversy

NASA Astrophysics Data System (ADS)

Giza, Piotr

2017-09-01

The paper explores possible influences that some developments in the field of branches of AI, called automated discovery and machine learning systems, might have upon some aspects of the old debate between Francis Bacon's inductivism and Karl Popper's falsificationism. Donald Gillies facetiously calls this controversy 'the duel of two English knights', and claims, after some analysis of historical cases of discovery, that Baconian induction had been used in science very rarely, or not at all, although he argues that the situation has changed with the advent of machine learning systems. (Some clarification of terms machine learning and automated discovery is required here. The key idea of machine learning is that, given data with associated outcomes, software can be trained to make those associations in future cases which typically amounts to inducing some rules from individual cases classified by the experts. Automated discovery (also called machine discovery) deals with uncovering new knowledge that is valuable for human beings, and its key idea is that discovery is like other intellectual tasks and that the general idea of heuristic search in problem spaces applies also to discovery tasks. However, since machine learning systems discover (very low-level) regularities in data, throughout this paper I use the generic term automated discovery for both kinds of systems. I will elaborate on this later on). Gillies's line of argument can be generalised: thanks to automated discovery systems, philosophers of science have at their disposal a new tool for empirically testing their philosophical hypotheses. Accordingly, in the paper, I will address the question, which of the two philosophical conceptions of scientific method is better vindicated in view of the successes and failures of systems developed within three major research programmes in the field: machine learning systems in the Turing tradition, normative theory of scientific discovery formulated by Herbert Simon

Predictors of timing of pregnancy discovery.

PubMed

McCarthy, Molly; Upadhyay, Ushma; Biggs, M Antonia; Anthony, Renaisa; Holl, Jennifer; Roberts, Sarah Cm

2018-04-01

Earlier pregnancy discovery is important in the context of prenatal and abortion care. We evaluated characteristics associated with later pregnancy discovery among women seeking abortion care. Data come from a survey of women seeking abortion care at four family planning facilities in Utah. The participants completed a survey during the state-mandated abortion information visit they are required to complete prior to having an abortion. The outcome in this study was pregnancy discovery before versus after 6 weeks since respondents' last menstrual period (LMP). We used logistic regression to estimate the relationship between sociodemographic and health-related independent variables of interest and pregnancy discovery before versus after 6 weeks. Among the 458 women in the sample, 28% discovered their pregnancy later than 6 weeks since LMP. Most (n=366, 80%) knew the exact date of their LMP and a significant minority estimated it (n=92, 20%). Those who estimated the date of their LMP had higher odds of later pregnancy discovery than those who knew the exact date (adjusted odds ratio (aOR)=1.81[1.07-3.07]). Those who used illicit drugs weekly, daily, or almost daily had higher odds of later pregnancy discovery (aOR=6.33[2.44, 16.40]). Women who did not track their menstrual periods and those who frequently used drugs had higher odds of discovering their pregnancies later. Women who estimated the date of their LMP and who frequently used drugs may benefit from strategies to help them recognize their pregnancies earlier and link them to care when they discover their pregnancies later. Copyright © 2017 Elsevier Inc. All rights reserved.

Tuning the electronic and the crystalline structure of LaBi by pressure: From extreme magnetoresistance to superconductivity

DOE PAGES

Tafti, F. F.; Torikachvili, M. S.; Stillwell, R. L.; ...

2017-01-10

Here, extreme magnetoresistance (XMR) in topological semimetals is a recent discovery which attracts attention due to its robust appearance in a growing number of materials. To search for a relation between XMR and superconductivity, we study the effect of pressure on LaBi. By increasing pressure, we observe the disappearance of XMR followed by the appearance of superconductivity at P ≈ 3.5 GPa. We find a region of coexistence between superconductivity and XMR in LaBi in contrast to other superconducting XMR materials. The suppression of XMR is correlated with increasing zero-field resistance instead of decreasing in-field resistance. At higher pressures, Pmore » ≈ 11 GPa, we find a structural transition from the face-centered cubic lattice to a primitive tetragonal lattice, in agreement with theoretical predictions. The relationship between extreme magnetoresistance, superconductivity, and structural transition in LaBi is discussed.« less

Robustness of disaggregate oil and gas discovery forecasting models

USGS Publications Warehouse

Attanasi, E.D.; Schuenemeyer, J.H.

1989-01-01

The trend in forecasting oil and gas discoveries has been to develop and use models that allow forecasts of the size distribution of future discoveries. From such forecasts, exploration and development costs can more readily be computed. Two classes of these forecasting models are the Arps-Roberts type models and the 'creaming method' models. This paper examines the robustness of the forecasts made by these models when the historical data on which the models are based have been subject to economic upheavals or when historical discovery data are aggregated from areas having widely differing economic structures. Model performance is examined in the context of forecasting discoveries for offshore Texas State and Federal areas. The analysis shows how the model forecasts are limited by information contained in the historical discovery data. Because the Arps-Roberts type models require more regularity in discovery sequence than the creaming models, prior information had to be introduced into the Arps-Roberts models to accommodate the influence of economic changes. The creaming methods captured the overall decline in discovery size but did not easily allow introduction of exogenous information to compensate for incomplete historical data. Moreover, the predictive log normal distribution associated with the creaming model methods appears to understate the importance of the potential contribution of small fields. ?? 1989.

Self-Consistent Atmosphere Models of the Most Extreme Hot Jupiters

NASA Astrophysics Data System (ADS)

Lothringer, Joshua; Barman, Travis

2018-01-01

We present a detailed look at self-consistent PHOENIX atmosphere models of the most highly irradiated hot Jupiters known to exist. These hot Jupiters typically have equilibrium temperatures approaching and sometimes exceeding 3000 K, orbiting A, F, and early-G type stars on orbits less than 0.03 AU (10x closer than Mercury is to the Sun). The most extreme example, KELT-9b, is the hottest known hot Jupiter with a measured dayside temperature of 4600 K. Many of the planets we model have recently attracted attention with high profile discoveries, including temperature inversions in WASP-33b and WASP-121, changing phase curve offsets possibly caused by magnetohydrodymanic effects in HAT-P-7b, and TiO in WASP-19b. Our modeling provides a look at the a priori expectations for these planets and helps us understand these recent discoveries. We show that, in the hottest cases, all molecules are dissociated down to relatively high pressures. These planets may have detectable temperature inversions, more akin to thermospheres than stratospheres in that an optical absorber like TiO or VO is not needed. Instead, the inversions are created by a lack of cooling in the IR combined with heating from atoms and ions at UV and blue optical wavelengths. We also reevaluate some of the assumptions that have been made in retrieval analyses of these planets.

Discovery Systems

NASA Technical Reports Server (NTRS)

Pell, Barney

2003-01-01

A viewgraph presentation on NASA's Discovery Systems Project is given. The topics of discussion include: 1) NASA's Computing Information and Communications Technology Program; 2) Discovery Systems Program; and 3) Ideas for Information Integration Using the Web.

KELT-FUN and the discovery of KELT-18b

NASA Astrophysics Data System (ADS)

McLeod, Kim K.; Melton, Casey; Stassun, Keivan G.; KELT Collaboration

2017-01-01

The Kilodegree Extremely Little Telescope (KELT) project is a ground-based, wide-field, synoptic sky survey whose primary goal is to discover exoplanets around bright (8 < V < 11) host stars. KELT photometric observations are carried out using two small robotic telescopes: KELT-North in Arizona, operating since 2005; and KELT-South in South Africa, operating since 2009. Once a transit candidate is identified by the survey telescopes, KELT relies on its Follow Up Network (KELT-FUN) of observatories to vet and characterize the systems by obtaining more precise light curves and radial-velocities. KELT-FUN now includes nearly 50 telescopes around the world and the photometric follow-up is carried out by a diverse set of partners at universities, small colleges, high schools, and private amateur facilities, often with the help of students. We describe KELT-FUN operations and announce the discovery of KELT-18b, a strongly-irradiated hot Jupiter orbiting a mid-F star.

Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities.

PubMed

Patham, Bhargavi; Duffy, Josh; Lane, Ariel; Davis, Richard C; Wipf, Peter; Fewell, Sheara W; Brodsky, Jeffrey L; Mensa-Wilmot, Kojo

2009-04-15

HAT (human African trypanosomiasis), caused by the protozoan parasite Trypanosoma brucei, is an emerging disease for which new drugs are needed. Expression of plasma membrane proteins [e.g. VSG (variant surface glycoprotein)] is crucial for the establishment and maintenance of an infection by T. brucei. Transport of a majority of proteins to the plasma membrane involves their translocation into the ER (endoplasmic reticulum). Thus inhibition of protein import into the ER of T. brucei would be a logical target for discovery of lead compounds against trypanosomes. We have developed a TbRM (T. brucei microsome) system that imports VSG_117 post-translationally. Using this system, MAL3-101, equisetin and CJ-21,058 were discovered to be small molecule inhibitors of VSG_117 translocation into the ER. These agents also killed bloodstream T. brucei in vitro; the concentrations at which 50% of parasites were killed (IC50) were 1.5 microM (MAL3-101), 3.3 microM (equisetin) and 7 microM (CJ-21,058). Thus VSG_117 import into TbRMs is a rapid and novel assay to identify 'new chemical entities' (e.g. MAL3-101, equisetin and CJ-21,058) for anti-trypanosome drug development.

Future Sky Surveys: New Discovery Frontiers

NASA Astrophysics Data System (ADS)

Tyson, J. Anthony; Borne, Kirk D.

2012-03-01

Driven by the availability of new instrumentation, there has been an evolution in astronomical science toward comprehensive investigations of new phenomena. Major advances in our understanding of the Universe over the history of astronomy have often arisen from dramatic improvements in our capability to observe the sky to greater depth, in previously unexplored wavebands, with higher precision, or with improved spatial, spectral, or temporal resolution. Substantial progress in the important scientific problems of the next decade (determining the nature of dark energy and dark matter, studying the evolution of galaxies and the structure of our own Milky Way, opening up the time domain to discover faint variable objects, and mapping both the inner and outer Solar System) can be achieved through the application of advanced data mining methods and machine learning algorithms operating on the numerous large astronomical databases that will be generated from a variety of revolutionary future sky surveys. Over the next decade, astronomy will irrevocably enter the era of big surveys and of really big telescopes. New sky surveys (some of which will produce petabyte-scale data collections) will begin their operations, and one or more very large telescopes (ELTs = Extremely Large Telescopes) will enter the construction phase. These programs and facilities will generate a remarkable wealth of data of high complexity, endowed with enormous scientific knowledge discovery potential. New parameter spaces will be opened, in multiple wavelength domains as well as the time domain, across wide areas of the sky, and down to unprecedented faint source flux limits. The synergies of grand facilities, massive data collections, and advanced machine learning algorithms will come together to enable discoveries within most areas of astronomical science, including Solar System, exo-planets, star formation, stellar populations, stellar death, galaxy assembly, galaxy evolution, quasar evolution

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...

Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method

PubMed Central

Niks, Irene; Gevers, Josette

2018-01-01

Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care. PMID:29438350

Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method.

PubMed

Niks, Irene; de Jonge, Jan; Gevers, Josette; Houtman, Irene

2018-02-13

Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care.

14 CFR 406.143 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 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 are...

14 CFR 406.143 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 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 are...

14 CFR 406.143 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 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 are...

14 CFR 406.143 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 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 are...

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 are...

Technology perspectives in the future exploration of extreme environments

NASA Astrophysics Data System (ADS)

Cutts, J.; Balint, T.; Kolawa, El.; Peterson, C.

2007-08-01

Solar System exploration is driven by high priority science goals and objectives at diverse destinations, as described in the NRC Decadal Survey and in NASA's 2006 Solar System Exploration (SSE) Roadmap. Proposed missions to these targets encounter extreme environments, including high or low temperatures, high pressure, corrosion, high heat flux, radiation and thermal cycling. These conditions are often coupled, such as low temperature and high radiation at Europa; and high temperature and high pressure near the surface of Venus. Mitigation of these environmental conditions frequently reaches beyond technologies developed for terrestrial applications, for example, by the automotive and oil industries. Therefore, space agencies require dedicated technology developments to enable these future missions. Within NASA, proposed missions are divided into three categories. Competed small (Discovery class) and medium (New Frontiers class) missions are cost capped, thus limiting significant technology developments. Therefore, large (Flagship class) missions are required not only to tackle key science questions which can't be addressed by smaller missions, but also to develop mission enabling technologies that can feed forward to smaller missions as well. In a newly completed extreme environment technology assessment at NASA, we evaluated technologies from the current State of Practice (SoP) to advanced concepts for proposed missions over the next decades. Highlights of this report are discussed here, including systems architectures, such as hybrid systems; protection systems; high temperature electronics; power generation and storage; mobility technologies; sample acquisition and mechanisms; and the need to test these technologies in relevant environments. It is expected that the findings - documented in detail in NASA's Extreme Environments Technologies report - would help identifying future technology investment areas, and in turn enable or enhance planned SSE missions

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

Recent development in software and automation tools for high-throughput discovery bioanalysis.

PubMed

Shou, Wilson Z; Zhang, Jun

2012-05-01

Bioanalysis with LC-MS/MS has been established as the method of choice for quantitative determination of drug candidates in biological matrices in drug discovery and development. The LC-MS/MS bioanalytical support for drug discovery, especially for early discovery, often requires high-throughput (HT) analysis of large numbers of samples (hundreds to thousands per day) generated from many structurally diverse compounds (tens to hundreds per day) with a very quick turnaround time, in order to provide important activity and liability data to move discovery projects forward. Another important consideration for discovery bioanalysis is its fit-for-purpose quality requirement depending on the particular experiments being conducted at this stage, and it is usually not as stringent as those required in bioanalysis supporting drug development. These aforementioned attributes of HT discovery bioanalysis made it an ideal candidate for using software and automation tools to eliminate manual steps, remove bottlenecks, improve efficiency and reduce turnaround time while maintaining adequate quality. In this article we will review various recent developments that facilitate automation of individual bioanalytical procedures, such as sample preparation, MS/MS method development, sample analysis and data review, as well as fully integrated software tools that manage the entire bioanalytical workflow in HT discovery bioanalysis. In addition, software tools supporting the emerging high-resolution accurate MS bioanalytical approach are also discussed.

Analyzing phenological extreme events over the past five decades in Germany

NASA Astrophysics Data System (ADS)

Schleip, Christoph; Menzel, Annette; Estrella, Nicole; Graeser, Philipp

2010-05-01

, 1990 and 2007 whereas exceptionally extreme late events are seen in the year 1970. Summer phases such as fruit ripening exhibit stronger shifts to early extremes than spring phases. Leaf colouring phases reveal increasing probability for late extremes. The with GEV estimated 100-year event of Picea, Pinus and Larix amount to extreme early events of about -27, -31.48 and -32.79 days, respectively. If we assume non-stationary minimum data we get a more extreme 100-year event of about -35.40 for Picea but associated with wider confidence intervals. The GEV is simply another probability distribution but for purposes of extreme analysis in phenology it should be considered as equally important as (if not more important than) the Gaussian PDF approach.

Unveiling the extreme nature of the hyper faint galaxy Virgo I

NASA Astrophysics Data System (ADS)

Crnojevic, Denija

2017-08-01

We request HST/ACS imaging to obtain a deep color-magnitude diagram of the newly discovered candidate Milky Way satellite Virgo I. With an estimated absolute magnitude of only M_V -0.8 and a Galactocentric radius of 90 kpc, Virgo I is one of the faintest and most distant dwarfs ever observed, and could be identified as a prototype ''hyper'' faint galaxy. The detailed characterization of the smallest inhabited dark matter subhalos is crucial to guide hierarchical galaxy formation models, and in particular to constrain reionization, the nature of the dark matter particle, etc. With the advent of deep wide-field, ground-based surveys, the potential of uncovering these lowest-mass galaxies is quickly turning into reality, as demonstrated by the discovery in the past two years of tens of new Local Group members in the ultra-faint regime (M_V>-8). Virgo I represents a new record in galaxy physical properties, and urges us to be prepared for the likely emergence of an entirely new class of such objects in the era of future wide-field surveys (e.g., LSST). Only high resolution HST observations can enable us to confirm the nature of Virgo I, providing significantly more accurate estimates for its distance and structural properties, when compared to the discovery Subaru/HyperSuprimeCam imaging. Our proposed dataset will constitute a fundamental step in the upcoming hunt for galaxies with similarly extreme properties.

Resource Discovery for Extreme Scale Collaboration (RDESC) Final Report - RPI/TWC - Year 3

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

Fox, Peter

The amount of data produced in the practice of science is growing rapidly. Despite the accumulation and demand for scientific data, relatively little is actually made available for the broader scientific community. We surmise that the root of the problem is the perceived difficulty to electronically publish scientific data and associated metadata in a way that makes it discoverable. We propose to exploit Semantic Web technologies and practices to make (meta)data discoverable and easy to publish. We share our experiences in curating metadata to illustrate both the flexibility of our approach and the pain of discovering data in the currentmore » research environment. We also make recommendations by concrete example of how data publishers can provide their (meta)data by adding some limited, additional markup to HTML pages on the Web. With little additional effort from data publishers, the difficulty of data discovery/access/sharing can be greatly reduced and the impact of research data greatly enhanced.« less

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.

Thermodynamics of extremal rotating thin shells in an extremal BTZ spacetime and the extremal black hole entropy

NASA Astrophysics Data System (ADS)

Lemos, José P. S.; Minamitsuji, Masato; Zaslavskii, Oleg B.

2017-02-01

In a (2 +1 )-dimensional spacetime with a negative cosmological constant, the thermodynamics and the entropy of an extremal rotating thin shell, i.e., an extremal rotating ring, are investigated. The outer and inner regions with respect to the shell are taken to be the Bañados-Teitelbom-Zanelli (BTZ) spacetime and the vacuum ground state anti-de Sitter spacetime, respectively. By applying the first law of thermodynamics to the extremal thin shell, one shows that the entropy of the shell is an arbitrary well-behaved function of the gravitational area A+ alone, S =S (A+). When the thin shell approaches its own gravitational radius r+ and turns into an extremal rotating BTZ black hole, it is found that the entropy of the spacetime remains such a function of A+, both when the local temperature of the shell at the gravitational radius is zero and nonzero. It is thus vindicated by this analysis that extremal black holes, here extremal BTZ black holes, have different properties from the corresponding nonextremal black holes, which have a definite entropy, the Bekenstein-Hawking entropy S (A+)=A/+4G , where G is the gravitational constant. It is argued that for extremal black holes, in particular for extremal BTZ black holes, one should set 0 ≤S (A+)≤A/+4G;i.e., the extremal black hole entropy has values in between zero and the maximum Bekenstein-Hawking entropy A/+4 G . Thus, rather than having just two entropies for extremal black holes, as previous results have debated, namely, 0 and A/+4 G , it is shown here that extremal black holes, in particular extremal BTZ black holes, may have a continuous range of entropies, limited by precisely those two entropies. Surely, the entropy that a particular extremal black hole picks must depend on past processes, notably on how it was formed. A remarkable relation between the third law of thermodynamics and the impossibility for a massive body to reach the velocity of light is also found. In addition, in the procedure, it

Exploring the Role of Receptor Flexibility in Structure-Based Drug Discovery

PubMed Central

Feixas, Ferran; Lindert, Steffen; Sinko, William; McCammon, J. Andrew

2015-01-01

The proper understanding of biomolecular recognition mechanisms that take place in a drug target is of paramount importance to improve the efficiency of drug discovery and development. The intrinsic dynamic character of proteins has a strong influence on biomolecular recognition mechanisms and models such as conformational selection have been widely used to account for this dynamic association process. However, conformational changes occurring in the receptor prior and upon association with other molecules are diverse and not obvious to predict when only a few structures of the receptor are available. In view of the prominent role of protein flexibility in ligand binding and its implications for drug discovery, it is of great interest to identify receptor conformations that play a major role in biomolecular recognition before starting rational drug design efforts. In this review, we discuss a number of recent advances in computer-aided drug discovery techniques that have been proposed to incorporate receptor flexibility into structure-based drug design. The allowance for receptor flexibility provided by computational techniques such as molecular dynamics simulations or enhanced sampling techniques helps to improve the accuracy of methods used to estimate binding affinities and, thus, such methods can contribute to the discovery of novel drug leads. PMID:24332165

Generalized extreme gust wind speeds distributions

USGS Publications Warehouse

Cheng, E.; Yeung, C.

2002-01-01

Since summer 1996, the US wind engineers are using the extreme gust (or 3-s gust) as the basic wind speed to quantify the destruction of extreme winds. In order to better understand these destructive wind forces, it is important to know the appropriate representations of these extreme gust wind speeds. Therefore, the purpose of this study is to determine the most suitable extreme value distributions for the annual extreme gust wind speeds recorded in large selected areas. To achieve this objective, we are using the generalized Pareto distribution as the diagnostic tool for determining the types of extreme gust wind speed distributions. The three-parameter generalized extreme value distribution function is, thus, reduced to either Type I Gumbel, Type II Frechet or Type III reverse Weibull distribution function for the annual extreme gust wind speeds recorded at a specific site.With the considerations of the quality and homogeneity of gust wind data collected at more than 750 weather stations throughout the United States, annual extreme gust wind speeds at selected 143 stations in the contiguous United States were used in the study. ?? 2002 Elsevier Science Ltd. All rights reserved.

A Millennial Challenge: Extremism in Uncertain Times

PubMed Central

Fiske, Susan T.

2014-01-01

This comment highlights the relevance and importance of the uncertainty-extremism topic, both scientifically and societally, identifies common themes, locates this work in a wider scientific and social context, describes what we now know and what we still do not, acknowledges some limitations, foreshadowing future directions, and discusses some potential policy relevance. Common themes emerge around the importance of social justice as sound anti-extremism policy. PMID:24511155

Controlling extreme events on complex networks

NASA Astrophysics Data System (ADS)

Chen, Yu-Zhong; Huang, Zi-Gang; Lai, Ying-Cheng

2014-08-01

Extreme events, a type of collective behavior in complex networked dynamical systems, often can have catastrophic consequences. To develop effective strategies to control extreme events is of fundamental importance and practical interest. Utilizing transportation dynamics on complex networks as a prototypical setting, we find that making the network ``mobile'' can effectively suppress extreme events. A striking, resonance-like phenomenon is uncovered, where an optimal degree of mobility exists for which the probability of extreme events is minimized. We derive an analytic theory to understand the mechanism of control at a detailed and quantitative level, and validate the theory numerically. Implications of our finding to current areas such as cybersecurity are discussed.

Chemical Discovery

ERIC Educational Resources Information Center

Brown, Herbert C.

1974-01-01

The role of discovery in the advance of the science of chemistry and the factors that are currently operating to handicap that function are considered. Examples are drawn from the author's work with boranes. The thesis that exploratory research and discovery should be encouraged is stressed. (DT)

"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…

Nutrition security under extreme events

NASA Astrophysics Data System (ADS)

Martinez, A.

2017-12-01

Nutrition security under extreme events. Zero hunger being one of the Sustainable Development Goal from the United Nations, food security has become a trending research topic. However extreme events impact on global food security is not yet 100% understood and there is a lack of comprehension of the underlying mechanisms of global food trade and nutrition security to improve countries resilience to extreme events. In a globalized world, food is still a highly regulated commodity and a strategic resource. A drought happening in a net food-exporter will have little to no effect on its own population but the repercussion on net food-importers can be extreme. In this project, we propose a methodology to describe and quantify the impact of a local drought to human health at a global scale. For this purpose, nutrition supply and global trade data from FAOSTAT have been used with domestic food production from national agencies and FAOSTAT, global precipitation from the Climate Research Unit and health data from the World Health Organization. A modified Herfindahl-Hirschman Index (HHI) has been developed to measure the level of resilience of one country to a drought happening in another country. This index describes how a country is dependent of importation and how diverse are its importation. Losses of production and exportation due to extreme events have been calculated using yield data and a simple food balance at country scale. Results show that countries the most affected by global droughts are the one with the highest dependency to one exporting country. Changes induced by droughts also disturbed their domestic proteins, fat and calories supply resulting most of the time in a higher intake of calories or fat over proteins.

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Discovery. 44.24 Section 44.24 Mineral... Discovery. Parties shall be governed in their conduct of discovery by appropriate provisions of the Federal... discovery. Alternative periods of time for discovery may be prescribed by the presiding administrative law...

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Discovery. 44.24 Section 44.24 Mineral... Discovery. Parties shall be governed in their conduct of discovery by appropriate provisions of the Federal... discovery. Alternative periods of time for discovery may be prescribed by the presiding administrative law...

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Discovery. 44.24 Section 44.24 Mineral... Discovery. Parties shall be governed in their conduct of discovery by appropriate provisions of the Federal... discovery. Alternative periods of time for discovery may be prescribed by the presiding administrative law...

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Discovery. 44.24 Section 44.24 Mineral... Discovery. Parties shall be governed in their conduct of discovery by appropriate provisions of the Federal... discovery. Alternative periods of time for discovery may be prescribed by the presiding administrative law...

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Discovery. 44.24 Section 44.24 Mineral... Discovery. Parties shall be governed in their conduct of discovery by appropriate provisions of the Federal... discovery. Alternative periods of time for discovery may be prescribed by the presiding administrative law...

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Discovery. 224.21 Section 224.21 Foreign....21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... parties, discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery...

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Discovery. 224.21 Section 224.21 Foreign....21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... parties, discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery...

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Discovery. 224.21 Section 224.21 Foreign....21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... parties, discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery...

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Discovery. 224.21 Section 224.21 Foreign....21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... parties, discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery...

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 224.21 Section 224.21 Foreign....21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of... parties, discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery...

Extreme insular dwarfism evolved in a mammoth.

PubMed

Herridge, Victoria L; Lister, Adrian M

2012-08-22

The insular dwarfism seen in Pleistocene elephants has come to epitomize the island rule; yet our understanding of this phenomenon is hampered by poor taxonomy. For Mediterranean dwarf elephants, where the most extreme cases of insular dwarfism are observed, a key systematic question remains unresolved: are all taxa phyletic dwarfs of a single mainland species Palaeoloxodon antiquus (straight-tusked elephant), or are some referable to Mammuthus (mammoths)? Ancient DNA and geochronological evidence have been used to support a Mammuthus origin for the Cretan 'Palaeoloxodon' creticus, but these studies have been shown to be flawed. On the basis of existing collections and recent field discoveries, we present new, morphological evidence for the taxonomic status of 'P'. creticus, and show that it is indeed a mammoth, most probably derived from Early Pleistocene Mammuthus meridionalis or possibly Late Pliocene Mammuthus rumanus. We also show that Mammuthus creticus is smaller than other known insular dwarf mammoths, and is similar in size to the smallest dwarf Palaeoloxodon species from Sicily and Malta, making it the smallest mammoth species known to have existed. These findings indicate that extreme insular dwarfism has evolved to a similar degree independently in two elephant lineages.

From bench to patient: model systems in drug discovery

PubMed Central

Breyer, Matthew D.; Look, A. Thomas; Cifra, Alessandra

2015-01-01

ABSTRACT Model systems, including laboratory animals, microorganisms, and cell- and tissue-based systems, are central to the discovery and development of new and better drugs for the treatment of human disease. In this issue, Disease Models & Mechanisms launches a Special Collection that illustrates the contribution of model systems to drug discovery and optimisation across multiple disease areas. This collection includes reviews, Editorials, interviews with leading scientists with a foot in both academia and industry, and original research articles reporting new and important insights into disease therapeutics. This Editorial provides a summary of the collection's current contents, highlighting the impact of multiple model systems in moving new discoveries from the laboratory bench to the patients' bedsides. PMID:26438689

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Discovery. 25.21 Section 25.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Discovery. 25.21 Section 25.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Discovery. 25.21 Section 25.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

5 CFR 185.122 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Discovery. 185.122 Section 185.122... § 185.122 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Discovery. 25.21 Section 25.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

5 CFR 185.122 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Discovery. 185.122 Section 185.122... § 185.122 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

5 CFR 185.122 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Discovery. 185.122 Section 185.122... § 185.122 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

5 CFR 185.122 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Discovery. 185.122 Section 185.122... § 185.122 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discovery. 25.21 Section 25.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the ALJ. The ALJ shall regulate the timing of discovery. (d...

39 CFR 952.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 39 Postal Service 1 2014-07-01 2014-07-01 false Discovery. 952.21 Section 952.21 Postal Service... AND LOTTERY ORDERS § 952.21 Discovery. (a) Voluntary discovery. The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure...

39 CFR 952.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 39 Postal Service 1 2013-07-01 2013-07-01 false Discovery. 952.21 Section 952.21 Postal Service... AND LOTTERY ORDERS § 952.21 Discovery. (a) Voluntary discovery. The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure...

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 3 2014-04-01 2014-04-01 false Discovery. 356.20 Section 356.20 Customs Duties... § 356.20 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery... sanctions proceeding. (b) Limitations on discovery. The administrative law judge shall place such limits...

39 CFR 952.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 39 Postal Service 1 2012-07-01 2012-07-01 false Discovery. 952.21 Section 952.21 Postal Service... AND LOTTERY ORDERS § 952.21 Discovery. (a) Voluntary discovery. The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure...

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 3 2013-04-01 2013-04-01 false Discovery. 356.20 Section 356.20 Customs Duties... § 356.20 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery... sanctions proceeding. (b) Limitations on discovery. The administrative law judge shall place such limits...

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 3 2012-04-01 2012-04-01 false Discovery. 356.20 Section 356.20 Customs Duties... § 356.20 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery... sanctions proceeding. (b) Limitations on discovery. The administrative law judge shall place such limits...

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 3 2011-04-01 2011-04-01 false Discovery. 356.20 Section 356.20 Customs Duties... § 356.20 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery... sanctions proceeding. (b) Limitations on discovery. The administrative law judge shall place such limits...

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 356.20 Section 356.20 Customs Duties... § 356.20 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery... sanctions proceeding. (b) Limitations on discovery. The administrative law judge shall place such limits...

37 CFR 42.224 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Discovery. 42.224 Section 42... Post-Grant Review § 42.224 Discovery. Notwithstanding the discovery provisions of subpart A: (a) Requests for additional discovery may be granted upon a showing of good cause as to why the discovery is...

37 CFR 42.224 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Discovery. 42.224 Section 42... Post-Grant Review § 42.224 Discovery. Notwithstanding the discovery provisions of subpart A: (a) Requests for additional discovery may be granted upon a showing of good cause as to why the discovery is...

The discovery and nature of the optical transient CSS100217:102913+404220

DOE PAGES

Drake, A. J.; Djorgovski, S. G.; Mahabal, A.; ...

2011-06-22

We report on the discovery and observations of the extremely luminous optical transient CSS100217:102913+404220 (CSS100217 hereafter). Spectroscopic observations showed that this transient was coincident with a galaxy at redshift z = 0.147 and reached an apparent magnitude of V ~ 16.3. After correcting for foreground Galactic extinction we determine the absolute magnitude to be M V = –22.7 approximately 45 days after maximum light. Over a period of 287 rest-frame days, this event had an integrated bolometric luminosity of 1.3 × 10 52 erg based on time-averaged bolometric corrections of ~15 from V- and R-band observations. Analysis of the pre-outburstmore » Sloan Digital Sky Survey (SDSS) spectrum of the source shows features consistent with a narrow-line Seyfert 1 galaxy. High-resolution Hubble Space Telescope and Keck follow-up observations show that the event occurred within 150 pc of the nucleus of the galaxy, suggesting a possible link to the active nuclear region. However, the rapid outburst along with photometric and spectroscopic evolution are much more consistent with a luminous supernova. Line diagnostics suggest that the host galaxy is undergoing significant star formation. We use extensive follow-up of the event along with archival Catalina Sky Survey NEO search and SDSS data to investigate the three most likely sources of such an event: (1) an extremely luminous supernova, (2) the tidal disruption of a star by the massive nuclear black hole, and (3) variability of the central active galactic nucleus (AGN). We find that CSS100217 was likely an extremely luminous Type IIn supernova and occurred within the range of the narrow-line region of an AGN. Here, we discuss how similar events may have been missed in past supernova surveys because of confusion with AGN activity.« less

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 3 2014-04-01 2014-04-01 false Discovery. 207.109 Section 207.109 Customs Duties... and Committee Proceedings § 207.109 Discovery. (a) Discovery methods. All parties may obtain discovery under such terms and limitations as the administrative law judge may order. Discovery may be by one or...

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 3 2011-04-01 2011-04-01 false Discovery. 207.109 Section 207.109 Customs Duties... and Committee Proceedings § 207.109 Discovery. (a) Discovery methods. All parties may obtain discovery under such terms and limitations as the administrative law judge may order. Discovery may be by one or...

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 3 2013-04-01 2013-04-01 false Discovery. 207.109 Section 207.109 Customs Duties... and Committee Proceedings § 207.109 Discovery. (a) Discovery methods. All parties may obtain discovery under such terms and limitations as the administrative law judge may order. Discovery may be by one or...

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 3 2012-04-01 2012-04-01 false Discovery. 207.109 Section 207.109 Customs Duties... and Committee Proceedings § 207.109 Discovery. (a) Discovery methods. All parties may obtain discovery under such terms and limitations as the administrative law judge may order. Discovery may be by one or...

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

XVIS: Visualization for the Extreme-Scale Scientific-Computation Ecosystem Final Scientific/Technical Report

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

Geveci, Berk; Maynard, Robert

The XVis project brings together the key elements of research to enable scientific discovery at extreme scale. Scientific computing will no longer be purely about how fast computations can be performed. Energy constraints, processor changes, and I/O limitations necessitate significant changes in both the software applications used in scientific computation and the ways in which scientists use them. Components for modeling, simulation, analysis, and visualization must work together in a computational ecosystem, rather than working independently as they have in the past. The XVis project brought together collaborators from predominant DOE projects for visualization on accelerators and combining their respectivemore » features into a new visualization toolkit called VTK-m.« less

Tales from the Paleoclimate Underground: Lessons Learned from Reconstructing Extreme Events

NASA Astrophysics Data System (ADS)

Frappier, A. E.

2017-12-01

Tracing patterns of paleoclimate extremes over the past two millennia is becoming ever more important in the effort to understand and predict costly weather hazards and their varied societal impacts. I present three paleoclimate vignettes from the past ten years of different paleotempestology projects I have worked on closely, illustrating our collective challenges and productive pathways in reconstructing rainfall extremes: temporal, spatial, and combining information from disparate proxies. Finally, I aim to share new results from modeling multiple extremes and hazards in Yucatan, a climate change hotspot.

Biomarker Discovery by Novel Sensors Based on Nanoproteomics Approaches

PubMed Central

Dasilva, Noelia; Díez, Paula; Matarraz, Sergio; González-González, María; Paradinas, Sara; Orfao, Alberto; Fuentes, Manuel

2012-01-01

During the last years, proteomics has facilitated biomarker discovery by coupling high-throughput techniques with novel nanosensors. In the present review, we focus on the study of label-based and label-free detection systems, as well as nanotechnology approaches, indicating their advantages and applications in biomarker discovery. In addition, several disease biomarkers are shown in order to display the clinical importance of the improvement of sensitivity and selectivity by using nanoproteomics approaches as novel sensors. PMID:22438764

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.

Choosing experiments to accelerate collective discovery

PubMed Central

Rzhetsky, Andrey; Foster, Jacob G.; Foster, Ian T.

2015-01-01

A scientist’s choice of research problem affects his or her personal career trajectory. Scientists’ combined choices affect the direction and efficiency of scientific discovery as a whole. In this paper, we infer preferences that shape problem selection from patterns of published findings and then quantify their efficiency. We represent research problems as links between scientific entities in a knowledge network. We then build a generative model of discovery informed by qualitative research on scientific problem selection. We map salient features from this literature to key network properties: an entity’s importance corresponds to its degree centrality, and a problem’s difficulty corresponds to the network distance it spans. Drawing on millions of papers and patents published over 30 years, we use this model to infer the typical research strategy used to explore chemical relationships in biomedicine. This strategy generates conservative research choices focused on building up knowledge around important molecules. These choices become more conservative over time. The observed strategy is efficient for initial exploration of the network and supports scientific careers that require steady output, but is inefficient for science as a whole. Through supercomputer experiments on a sample of the network, we study thousands of alternatives and identify strategies much more efficient at exploring mature knowledge networks. We find that increased risk-taking and the publication of experimental failures would substantially improve the speed of discovery. We consider institutional shifts in grant making, evaluation, and publication that would help realize these efficiencies. PMID:26554009

Knowledge Discovery and Data Mining: An Overview

NASA Technical Reports Server (NTRS)

Fayyad, U.

1995-01-01

The process of knowledge discovery and data mining is the process of information extraction from very large databases. Its importance is described along with several techniques and considerations for selecting the most appropriate technique for extracting information from a particular data set.

Rainfall extremes from TRMM data and the Metastatistical Extreme Value Distribution

NASA Astrophysics Data System (ADS)

Zorzetto, Enrico; Marani, Marco

2017-04-01

A reliable quantification of the probability of weather extremes occurrence is essential for designing resilient water infrastructures and hazard mitigation measures. However, it is increasingly clear that the presence of inter-annual climatic fluctuations determines a substantial long-term variability in the frequency of occurrence of extreme events. This circumstance questions the foundation of the traditional extreme value theory, hinged on stationary Poisson processes or on asymptotic assumptions to derive the Generalized Extreme Value (GEV) distribution. We illustrate here, with application to daily rainfall, a new approach to extreme value analysis, the Metastatistical Extreme Value Distribution (MEVD). The MEVD relaxes the above assumptions and is based on the whole distribution of daily rainfall events, thus allowing optimal use of all available observations. Using a global dataset of rain gauge observations, we show that the MEVD significantly outperforms the Generalized Extreme Value distribution, particularly for long average recurrence intervals and when small samples are available. The latter property suggests MEVD to be particularly suited for applications to satellite rainfall estimates, which only cover two decades, thus making extreme value estimation extremely challenging. Here we apply MEVD to the TRMM TMPA 3B42 product, an 18-year dataset of remotely-sensed daily rainfall providing a quasi-global coverage. Our analyses yield a global scale mapping of daily rainfall extremes and of their distributional tail properties, bridging the existing large gaps in ground-based networks. Finally, we illustrate how our global-scale analysis can provide insight into how properties of local rainfall regimes affect tail estimation uncertainty when using the GEV or MEVD approach. We find a dependence of the estimation uncertainty, for both the GEV- and MEV-based approaches, on the average annual number and on the inter-annual variability of rainy days. In

On the Discovery of Evolving Truth

PubMed Central

Li, Yaliang; Li, Qi; Gao, Jing; Su, Lu; Zhao, Bo; Fan, Wei; Han, Jiawei

2015-01-01

In the era of big data, information regarding the same objects can be collected from increasingly more sources. Unfortunately, there usually exist conflicts among the information coming from different sources. To tackle this challenge, truth discovery, i.e., to integrate multi-source noisy information by estimating the reliability of each source, has emerged as a hot topic. In many real world applications, however, the information may come sequentially, and as a consequence, the truth of objects as well as the reliability of sources may be dynamically evolving. Existing truth discovery methods, unfortunately, cannot handle such scenarios. To address this problem, we investigate the temporal relations among both object truths and source reliability, and propose an incremental truth discovery framework that can dynamically update object truths and source weights upon the arrival of new data. Theoretical analysis is provided to show that the proposed method is guaranteed to converge at a fast rate. The experiments on three real world applications and a set of synthetic data demonstrate the advantages of the proposed method over state-of-the-art truth discovery methods. PMID:26705502

39 CFR 963.14 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 39 Postal Service 1 2012-07-01 2012-07-01 false Discovery. 963.14 Section 963.14 Postal Service... PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a... such discovery as he or she deems reasonable and necessary. Discovery may include one or more of the...

39 CFR 963.14 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 39 Postal Service 1 2013-07-01 2013-07-01 false Discovery. 963.14 Section 963.14 Postal Service... PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a... such discovery as he or she deems reasonable and necessary. Discovery may include one or more of the...

39 CFR 963.14 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 39 Postal Service 1 2014-07-01 2014-07-01 false Discovery. 963.14 Section 963.14 Postal Service... PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a... such discovery as he or she deems reasonable and necessary. Discovery may include one or more of the...

39 CFR 963.14 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 39 Postal Service 1 2011-07-01 2011-07-01 false Discovery. 963.14 Section 963.14 Postal Service... PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a... such discovery as he or she deems reasonable and necessary. Discovery may include one or more of the...

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... PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a... such discovery as he or she deems reasonable and necessary. Discovery may include one or more of the...

Predicting crystal structures and properties of matter under extreme conditions via quantum mechanics: The pressure is on

DOE PAGES

Zurek, Eva; Grochala, Wojciech

2014-11-27

Experimental studies of compressed matter are now routinely conducted at pressures exceeding 1 mln atm (100 GPa) and occasionally they even surpass 10 mln atm (1 TPa). The structure and properties of solids that have been so significantly squeezed differ considerably from those know at ambient pressures (1 atm), often times leading to new and unexpected physics. Chemical reactivity is also substantially altered in the extreme pressure regime. In this feature paper we describe how synergy between theory and experiment can pave the road towards new experimental discoveries. Because chemical rules-of-thumb established at 1 atm often fail to predict themore » structures of solids under high pressure, automated crystal structure prediction (CSP) methods have been increasingly employed. After outlining the most important CSP techniques, we showcase a few examples from the recent literature that exemplify just how useful theory can be as an aid in the interpretation of experimental data, describe exciting theoretical predictions that are guiding experiment, and discuss when the computational methods that are currently routinely employed fail. Lastly, we forecast important problems that will be targeted by theory as theoretical methods undergo rapid development, along with the simultaneous increase of computational power.« less

Meeting report on the Alzheimer’s Drug Discovery Foundation 14th International Conference on Alzheimer’s Drug Discovery

PubMed Central

2014-01-01

The Alzheimer’s Drug Discovery Foundation’s 14th International Conference on Alzheimer’s Drug Discovery was held on 9 and 10 September in Jersey City, NJ, USA. This annual meeting highlights novel therapeutic approaches supported by the Alzheimer’s Drug Discovery Foundation in development for Alzheimer’s disease and related dementias.

From damage to discovery via virtual unwrapping: Reading the scroll from En-Gedi

PubMed Central

Seales, William Brent; Parker, Clifford Seth; Segal, Michael; Tov, Emanuel; Shor, Pnina; Porath, Yosef

2016-01-01

Computer imaging techniques are commonly used to preserve and share readable manuscripts, but capturing writing locked away in ancient, deteriorated documents poses an entirely different challenge. This software pipeline—referred to as “virtual unwrapping”—allows textual artifacts to be read completely and noninvasively. The systematic digital analysis of the extremely fragile En-Gedi scroll (the oldest Pentateuchal scroll in Hebrew outside of the Dead Sea Scrolls) reveals the writing hidden on its untouchable, disintegrating sheets. Our approach for recovering substantial ink-based text from a damaged object results in readable columns at such high quality that serious critical textual analysis can occur. Hence, this work creates a new pathway for subsequent textual discoveries buried within the confines of damaged materials. PMID:27679821

Trellis Tone Modulation Multiple-Access for Peer Discovery in D2D Networks

PubMed Central

Lim, Chiwoo; Kim, Sang-Hyo

2018-01-01

In this paper, a new non-orthogonal multiple-access scheme, trellis tone modulation multiple-access (TTMMA), is proposed for peer discovery of distributed device-to-device (D2D) communication. The range and capacity of discovery are important performance metrics in peer discovery. The proposed trellis tone modulation uses single-tone transmission and achieves a long discovery range due to its low Peak-to-Average Power Ratio (PAPR). The TTMMA also exploits non-orthogonal resource assignment to increase the discovery capacity. For the multi-user detection of superposed multiple-access signals, a message-passing algorithm with supplementary schemes are proposed. With TTMMA and its message-passing demodulation, approximately 1.5 times the number of devices are discovered compared to the conventional frequency division multiple-access (FDMA)-based discovery. PMID:29673167

Trellis Tone Modulation Multiple-Access for Peer Discovery in D2D Networks.

PubMed

Lim, Chiwoo; Jang, Min; Kim, Sang-Hyo

2018-04-17

In this paper, a new non-orthogonal multiple-access scheme, trellis tone modulation multiple-access (TTMMA), is proposed for peer discovery of distributed device-to-device (D2D) communication. The range and capacity of discovery are important performance metrics in peer discovery. The proposed trellis tone modulation uses single-tone transmission and achieves a long discovery range due to its low Peak-to-Average Power Ratio (PAPR). The TTMMA also exploits non-orthogonal resource assignment to increase the discovery capacity. For the multi-user detection of superposed multiple-access signals, a message-passing algorithm with supplementary schemes are proposed. With TTMMA and its message-passing demodulation, approximately 1.5 times the number of devices are discovered compared to the conventional frequency division multiple-access (FDMA)-based discovery.

MSClique: Multiple Structure Discovery through the Maximum Weighted Clique Problem.

PubMed

Sanroma, Gerard; Penate-Sanchez, Adrian; Alquézar, René; Serratosa, Francesc; Moreno-Noguer, Francesc; Andrade-Cetto, Juan; González Ballester, Miguel Ángel

2016-01-01

We present a novel approach for feature correspondence and multiple structure discovery in computer vision. In contrast to existing methods, we exploit the fact that point-sets on the same structure usually lie close to each other, thus forming clusters in the image. Given a pair of input images, we initially extract points of interest and extract hierarchical representations by agglomerative clustering. We use the maximum weighted clique problem to find the set of corresponding clusters with maximum number of inliers representing the multiple structures at the correct scales. Our method is parameter-free and only needs two sets of points along with their tentative correspondences, thus being extremely easy to use. We demonstrate the effectiveness of our method in multiple-structure fitting experiments in both publicly available and in-house datasets. As shown in the experiments, our approach finds a higher number of structures containing fewer outliers compared to state-of-the-art methods.

Simple animal models for amyotrophic lateral sclerosis drug discovery.

PubMed

Patten, Shunmoogum A; Parker, J Alex; Wen, Xiao-Yan; Drapeau, Pierre

2016-08-01

Simple animal models have enabled great progress in uncovering the disease mechanisms of amyotrophic lateral sclerosis (ALS) and are helping in the selection of therapeutic compounds through chemical genetic approaches. Within this article, the authors provide a concise overview of simple model organisms, C. elegans, Drosophila and zebrafish, which have been employed to study ALS and discuss their value to ALS drug discovery. In particular, the authors focus on innovative chemical screens that have established simple organisms as important models for ALS drug discovery. There are several advantages of using simple animal model organisms to accelerate drug discovery for ALS. It is the authors' particular belief that the amenability of simple animal models to various genetic manipulations, the availability of a wide range of transgenic strains for labelling motoneurons and other cell types, combined with live imaging and chemical screens should allow for new detailed studies elucidating early pathological processes in ALS and subsequent drug and target discovery.

Quantifying the relationship between extreme air pollution events and extreme weather events

NASA Astrophysics Data System (ADS)

Zhang, Henian; Wang, Yuhang; Park, Tae-Won; Deng, Yi

2017-05-01

Extreme weather events can strongly affect surface air quality, which has become a major environmental factor to affect human health. Here, we examined the relationship between extreme ozone and PM2.5 (particular matter with an aerodynamic diameter less than 2.5 μm) events and the representative meteorological parameters such as daily maximum temperature (Tmax), minimum relative humidity (RHmin), and minimum wind speed (Vmin), using the location-specific 95th or 5th percentile threshold derived from historical reanalysis data (30 years for ozone and 10 years for PM2.5). We found that ozone and PM2.5 extremes were decreasing over the years, reflecting EPA's tightened standards and effort on reducing the corresponding precursor's emissions. Annual ozone and PM2.5 extreme days were highly correlated with Tmax and RHmin, especially in the eastern U.S. They were positively (negatively) correlated with Vmin in urban (rural and suburban) stations. The overlapping ratios of ozone extreme days with Tmax were fairly constant, about 32%, and tended to be high in fall and low in winter. Ozone extreme days were most sensitive to Tmax, then RHmin, and least sensitive to Vmin. The majority of ozone extremes occurred when Tmax was between 300 K and 320 K, RHmin was less than 40%, and Vmin was less than 3 m/s. The number of annual extreme PM2.5 days was highly positively correlated with the extreme RHmin/Tmax days, with correlation coefficient between PM2.5/RHmin highest in urban and suburban regions and the correlation coefficient between PM2.5/Tmax highest in rural area. Tmax has more impact on PM2.5 extreme over the eastern U.S. Extreme PM2.5 days were more likely to occur at low RH conditions in the central and southeastern U.S., especially during spring time, and at high RH conditions in the northern U.S. and the Great Plains. Most extreme PM2.5 events occurred when Tmax was between 300 K and 320 K and RHmin was between 10% and 50%. Extreme PM2.5 days usually occurred when

Hierarchical virtual screening approaches in small molecule drug discovery.

PubMed

Kumar, Ashutosh; Zhang, Kam Y J

2015-01-01

Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery. Copyright © 2014 Elsevier Inc. All rights reserved.

Choosing experiments to accelerate collective discovery

DOE PAGES

Rzhetsky, Andrey; Foster, Jacob G.; Foster, Ian T.; ...

2015-11-24

Scientists perform a tiny subset of all possible experiments. What characterizes the experiments they choose? What are the consequences of those choices for the pace of scientific discovery? We model scientific knowledge as a network and science as a sequence of experiments designed to gradually uncover it. By analyzing millions of biomedical articles published over 30 y, we find that biomedical scientists pursue conservative research strategies exploring the local neighborhood of central, important molecules. Although such strategies probably serve scientific careers, we show that they slow scientific advance, especially in mature fields, where more risk and less redundant experimentation wouldmore » accelerate discovery of the network. Lastly, we also consider institutional arrangements that could help science pursue these more efficient strategies.« less

Predicate Oriented Pattern Analysis for Biomedical Knowledge Discovery

PubMed Central

Shen, Feichen; Liu, Hongfang; Sohn, Sunghwan; Larson, David W.; Lee, Yugyung

2017-01-01

In the current biomedical data movement, numerous efforts have been made to convert and normalize a large number of traditional structured and unstructured data (e.g., EHRs, reports) to semi-structured data (e.g., RDF, OWL). With the increasing number of semi-structured data coming into the biomedical community, data integration and knowledge discovery from heterogeneous domains become important research problem. In the application level, detection of related concepts among medical ontologies is an important goal of life science research. It is more crucial to figure out how different concepts are related within a single ontology or across multiple ontologies by analysing predicates in different knowledge bases. However, the world today is one of information explosion, and it is extremely difficult for biomedical researchers to find existing or potential predicates to perform linking among cross domain concepts without any support from schema pattern analysis. Therefore, there is a need for a mechanism to do predicate oriented pattern analysis to partition heterogeneous ontologies into closer small topics and do query generation to discover cross domain knowledge from each topic. In this paper, we present such a model that predicates oriented pattern analysis based on their close relationship and generates a similarity matrix. Based on this similarity matrix, we apply an innovated unsupervised learning algorithm to partition large data sets into smaller and closer topics and generate meaningful queries to fully discover knowledge over a set of interlinked data sources. We have implemented a prototype system named BmQGen and evaluate the proposed model with colorectal surgical cohort from the Mayo Clinic. PMID:28983419

19 CFR 210.33 - Failure to make or cooperate in discovery; sanctions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Failure to make or cooperate in discovery; sanctions. 210.33 Section 210.33 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Discovery and Compulsory Process...

A discovery of extremely-enriched boehmite from coal in the Junger Coalfield, the northeastern Ordos Basin

USGS Publications Warehouse

Dai, S.; Ren, D.; Li, S.; Chou, C.

2006-01-01

The authors found an extremely-enriched boehmite and its associated minerals for the first time in the super-thick No. 6 coal seam from the Junger Coalfield in the northeastern Ordos Basin by using technologies including the X-ray diffraction analysis (XRD), scanning electron microscope equipped with an energy dispersive X-ray spectrometer, and optical microscope. The content of boehmite is as high as 13.1%, and the associated minerals are goyazite, zircon, rutile, goethite, galena, clausthalite, and selenio-galena. The heavy minerals assemblage is similar to that in the bauxite of the Benxi Formation from North China. The high boehmite in coal is mainly from weathering crust bauxite of the Benxi Formation from the northeastern coal-accumulation basin. The gibbsite colloidstone solution was removed from bauxite to the peat mire, and boehmite was formed via compaction and dehydration of gibbsite colloidstone solution in the period of peat accumulation and early period of diagenesis.

Drug discovery in the next millennium.

PubMed

Ohlstein, E H; Ruffolo, R R; Elliott, J D

2000-01-01

Selection and validation of novel molecular targets have become of paramount importance in light of the plethora 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. This review addresses these technological advances as well as several new areas that have been created by necessity to deal with this new paradigm, such as bioinformatics, cheminformatics, and functional genomics. With many of these key components of future drug discovery now in place, it is possible to map out a critical path for this process that will be used into the new millennium.

From bench to patient: model systems in drug discovery.

PubMed

Breyer, Matthew D; Look, A Thomas; Cifra, Alessandra

2015-10-01

Model systems, including laboratory animals, microorganisms, and cell- and tissue-based systems, are central to the discovery and development of new and better drugs for the treatment of human disease. In this issue, Disease Models & Mechanisms launches a Special Collection that illustrates the contribution of model systems to drug discovery and optimisation across multiple disease areas. This collection includes reviews, Editorials, interviews with leading scientists with a foot in both academia and industry, and original research articles reporting new and important insights into disease therapeutics. This Editorial provides a summary of the collection's current contents, highlighting the impact of multiple model systems in moving new discoveries from the laboratory bench to the patients' bedsides. © 2015. Published by The Company of Biologists Ltd.

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 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 in...

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 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 in...

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 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 in...

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 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 in...

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 in...

Revisiting lab-on-a-chip technology for drug discovery.

PubMed

Neuži, Pavel; Giselbrecht, Stefan; Länge, Kerstin; Huang, Tony Jun; Manz, Andreas

2012-08-01

The field of microfluidics or lab-on-a-chip technology aims to improve and extend the possibilities of bioassays, cell biology and biomedical research based on the idea of miniaturization. Microfluidic systems allow more accurate modelling of physiological situations for both fundamental research and drug development, and enable systematic high-volume testing for various aspects of drug discovery. Microfluidic systems are in development that not only model biological environments but also physically mimic biological tissues and organs; such 'organs on a chip' could have an important role in expediting early stages of drug discovery and help reduce reliance on animal testing. This Review highlights the latest lab-on-a-chip technologies for drug discovery and discusses the potential for future developments in this field.

A platform for the discovery of new macrolide antibiotics

NASA Astrophysics Data System (ADS)

Seiple, Ian B.; Zhang, Ziyang; Jakubec, Pavol; Langlois-Mercier, Audrey; Wright, Peter M.; Hog, Daniel T.; Yabu, Kazuo; Allu, Senkara Rao; Fukuzaki, Takehiro; Carlsen, Peter N.; Kitamura, Yoshiaki; Zhou, Xiang; Condakes, Matthew L.; Szczypiński, Filip T.; Green, William D.; Myers, Andrew G.

2016-05-01

The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture.

Discovery of potent HIV-1 non-nucleoside reverse transcriptase inhibitors from arylthioacetanilide structural motif.

PubMed

Li, Wenxin; Li, Xiao; De Clercq, Erik; Zhan, Peng; Liu, Xinyong

2015-09-18

The poor pharmacokinetics, side effects and particularly the rapid emergence of drug resistance compromise the efficiency of the clinically used anti-HIV drugs. Therefore, the discovery of novel and effective NNRTIs is still an extremely primary mission. Arylthioacetanilide family is one of the highly active HIV-1 NNRTIs against wide-type (WT) HIV-1 and a wide range of drug-resistant mutant strains. Especially, VRX-480773 and RDEA806 have been chosen as candidates for further clinical studies. In this article, we review the discovery and development of the arylthioacetanilides, and, especially, pay much attention to the structural modifications, SARs conclusions and molecular modeling. Moreover, several medicinal chemistry strategies to overcome drug resistance involved in the optimization process of arylthioacetanilides are highlighted, providing valuable clues for further investigations. Copyright © 2015 Elsevier Masson SAS. All rights reserved.