The discovery of the tau lepton: Part 1, The early history through 1975; Part 2, Confirmation of the discovery and measurement of major properties, 1976--1982

International Nuclear Information System (INIS)

Perl, M.L.

1994-08-01

Several previous papers have given the history of the discovery of the τ lepton at the Stanford Linear Accelerator Center (SLAC). These papers emphasized (a) the experiments which led to our 1975 publication of the first evidence for the existence of the τ, (b) the subsequent experiments which confirmed the existence of the r, and (c) the experiments which elucidated the major properties of the τ. That history will be summarized in Part 2 of this talk. In this Part 1, I describe the earlier thoughts and work of myself and my colleagues at SLAC in the 1960's and early 1970's which led to the discovery. I also describe the theoretical and experimental events in particle physics in the 1960's in which our work was immersed. I will also try to describe for the younger generations of particle physicists, the atmosphere in the 1960's. That was before the elucidation of the quark model of hadrons, before the development of the concept of particle generations The experimental paths to program we hot as clear as they are today and we had to cast a wide experimental net

The Discovery of the Tau Lepton: Part 1, The Early History Through 1975; Part 2, Confirmation of the Discovery and Measurement of Major Properties, 1976--1982

Science.gov (United States)

Perl, M. L.

1994-08-01

Several previous papers have given the history of the discovery of the {tau} lepton at the Stanford Linear Accelerator Center (SLAC). These papers emphasized (a) the experiments which led to our 1975 publication of the first evidence for the existence of the {tau}, (b) the subsequent experiments which confirmed the existence of the r, and (c) the experiments which elucidated the major properties of the {tau}. That history will be summarized in Part 2 of this talk. In this Part 1, I describe the earlier thoughts and work of myself and my colleagues at SLAC in the 1960's and early 1970's which led to the discovery. I also describe the theoretical and experimental events in particle physics in the 1960's in which our work was immersed. I will also try to describe for the younger generations of particle physicists, the atmosphere in the 1960's. That was before the elucidation of the quark model of hadrons, before the development of the concept of particle generations The experimental paths to program we hot as clear as they are today and we had to cast a wide experimental net.

What Marketing Strategy for Sacred Geometry Discoveries to Make Archaeotourism Work?

OpenAIRE

Mulaj, Isa

2015-01-01

Archaeotourism can take place in two main forms: i) on site or locations of discoveries; and ii) assembling the discoveries into museums or exhibitions. Given that the first option in Kosovo has not proven viable, a marketing strategy went on to be explored for the latter in broad terms by taking into account Bronze Age artifacts with engravings from the sacred geometry discovered by the Author of this paper during 2013-14, which were the work of ancient Illyrians. Yet, the results suggest a ...

Impaired social decision making in patients with major depressive disorder.

Science.gov (United States)

Wang, Yun; Zhou, Yuan; Li, Shu; Wang, Peng; Wu, Guo-Wei; Liu, Zhe-Ning

2014-01-23

Abnormal decision-making processes have been observed in patients with major depressive disorder (MDD). However, it is unresolved whether MDD patients show abnormalities in decision making in a social interaction context, in which decisions have actual influences on both the self-interests of the decision makers per se and those of their partners. Using a well-studied ultimatum game (UG), which is frequently used to investigate social interaction behavior, we examined whether MDD can be associated with abnormalities in social decision-making behavior by comparing the acceptance rates of MDD patients (N = 14) with those of normal controls (N = 19). The acceptance rates of the patients were lower than those of the normal controls. Additionally, unfair proposals were accepted at similar rates from computer partners and human partners in the MDD patients, unlike the acceptance rates in the normal controls, who were able to discriminatively treat unfair proposals from computer partners and human partners. Depressed patients show abnormal decision-making behavior in a social interaction context. Several possible explanations, such as increased sensitivity to fairness, negative emotional state and disturbed affective cognition, have been proposed to account for the abnormal social decision-making behavior in patients with MDD. This aberrant social decision-making behavior may provide a new perspective in the search to find biomarkers for the diagnosis and prognosis of MDD.

The need for operating guidelines and a decision making framework applicable to the discovery of non-intelligent extraterrestrial life

Science.gov (United States)

Race, Margaret S.; Randolph, Richard O.

While formal principles have been adopted for the eventuality of detecting intelligent life in our galaxy (SETI Principles), no such guidelines exist for the discovery of non-intelligent extraterrestrial life within the solar system. Current scientifically based planetary protection policies for solar system exploration address how to undertake exploration, but do not provide clear guidance on what to do if and when life is detected. Considering that martian life could be detected under several different robotic and human exploration scenarios in the coming decades, it is appropriate to anticipate how detection of non-intelligent, microbial life could impact future exploration missions and activities, especially on Mars. This paper discusses a proposed set of interim guidelines based loosely on the SETI Principles and addresses issues extending from the time of discovery through future handling and treatment of extraterrestrial life on Mars or elsewhere. Based on an analysis of both scientific and ethical considerations, there is a clear need for developing operating protocols applicable at the time of discovery and a decision making framework that anticipates future missions and activities, both robotic and human. There is growing scientific confidence that the discovery of extraterrestrial life in some form is nearly inevitable. If and when life is discovered beyond Earth, non-scientific dimensions may strongly influence decisions about the nature and scope of future missions and activities. It is appropriate to encourage international discussion and consideration of the issues prior to an event of such historical significance.

Toxins and drug discovery.

Science.gov (United States)

Harvey, Alan L

2014-12-15

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

DISCOVERY OF A MAKEMAKEAN MOON

Energy Technology Data Exchange (ETDEWEB)

Parker, Alex H.; Buie, Marc W. [Southwest Research Institute, 1050 Walnut Street, Suite 300, Boulder, CO 80302 (United States); Grundy, Will M. [Lowell Observatory, Flagstaff, AZ (United States); Noll, Keith S., E-mail: aparker@boulder.swri.edu [NASA Goddard Space Flight Center, Greenbelt, MD (United States)

2016-07-01

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

Discovery of a Makemakean Moon

Science.gov (United States)

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

2016-01-01

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

Socratic Questioning-Guided Discovery

Directory of Open Access Journals (Sweden)

M. Hakan Türkçapar

2012-04-01

Full Text Available “Socratic Method” is a way of teaching philosophical thinking and knowledge by asking questions which was used by antique period greek philosopher Socrates. Socrates was teaching knowledge to his followers by asking questions and the conversation between them was named “Socratic Dialogues”. In this meaning, no novel knowledge is taught to the individual but only what is formerly known is reminded and rediscovered. The form of socratic questioning which is used during the process of cognitive behavioral therapy is known as Guided Discovery. In this method it is aimed to make the client notice the piece of knowledge which he could notice but is not aware with a series of questions. Socratic method or guided discovery consists of several steps which are: Identifying the problem by listening to the client and making reflections, finding alternatives by examining and evaluating, reidentification by using the newly found information and questioning the old distorted belief and reaching to a conclusion and applying it. Question types used during these procedures are, questions for gaining information, questions revealing the meanings, questions revealing the beliefs, questions about behaviours during the similar past experiences, analyse questions and analytic synthesis questions. In order to make the patient feel understood it is important to be empathetic and summarising the problem during the interview. In this text, steps of Socratic Questioning-Guided Discovery will be reviewed with sample dialogues after eachstep. [JCBPR 2012; 1(1.000: 15-20

The discovery of radioactivity: the centenary

International Nuclear Information System (INIS)

Patil, S.K.

1995-01-01

In the last decade of the nineteenth century, a number of fundamental discoveries of outstanding importance were made unexpectedly which marked the beginning of a new era in physics. A cascade of spectacular discoveries began with the announcement of the discovery of x-rays by Roentgen followed by the discoveries, in quick succession, of radioactivity by Becquerel, of Zeeman effect, of electron by J.J. Thomson, and of polonium and radium by the Curies. Both x-rays and radioactivity have wide applications in scientific, medical and industrial fields and have made outstanding contribution to the advancement of human knowledge and welfare. Radioactivity is well known and no other discovery in the field of physics or chemistry has had a more profound effect on our fundamental knowledge of nature. Present article, on the occasion of the centenary of the discovery of radioactivity, makes an attempt to describe some glimpses of the history of radioactivity. (author). 59 refs

Discovery of the Collaborative Nature of Science with Undergraduate Science Majors and Non-Science Majors through the Identification of Microorganisms Enriched in Winogradsky Columns

Directory of Open Access Journals (Sweden)

Jasmine Ramirez

2015-08-01

Full Text Available Today’s science classrooms are addressing the need for non-scientists to become scientifically literate. A key aspect includes the recognition of science as a process for discovery. This process relies upon interdisciplinary collaboration. We designed a semester-long collaborative exercise that allows science majors taking a general microbiology course and non-science majors taking an introductory environmental science course to experience collaboration in science by combining their differing skill sets to identify microorganisms enriched in Winogradsky columns. These columns are self-sufficient ecosystems that allow researchers to study bacterial populations under specified environmental conditions. Non-science majors identified phototrophic bacteria enriched in the column by analyzing the signature chlorophyll absorption spectra whereas science majors used 16S rRNA gene sequencing to identify the general bacterial diversity. Students then compiled their results and worked together to generate lab reports with their final conclusions identifying the microorganisms present in their column. Surveys and lab reports were utilized to evaluate the learning objectives of this activity. In pre-surveys, nonmajors’ and majors’ answers diverged considerably, with majors providing responses that were more accurate and more in line with the working definition of collaboration. In post-surveys, the answers between majors and nonmajors converged, with both groups providing accurate responses. Lab reports showed that students were able to successfully identify bacteria present in the columns. These results demonstrate that laboratory exercises designed to group students across disciplinary lines can be an important tool in promoting science education across disciplines. Editor's Note:The ASM advocates that students must successfully demonstrate the ability to explain and practice safe laboratory techniques. For more information, read the laboratory

The Johns Hopkins Bloomberg School of Public Health: A Brief History of a Century of Epidemiologic Discovery.

Science.gov (United States)

Sommer, Alfred

2016-03-01

During its first century, the Johns Hopkins University Bloomberg School of Public Health has been home to several faculty members who have played leading roles in defining and expanding the field and science of epidemiology. They have done so by training leaders in the field, creating new methods and applications, and making relevant discoveries in the worlds of infectious and chronic diseases. These methodologic innovations and discoveries underlie many of today's major health policies and practices. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Biomarker Gene Signature Discovery Integrating Network Knowledge

Directory of Open Access Journals (Sweden)

Holger Fröhlich

2012-02-01

Full Text Available Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step towards a better personalized medicine. During the last decade various methods, mainly coming from the machine learning or statistical domain, have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Here we review the current state of research in this field by giving an overview about so-far proposed approaches.

Get Involved in Planetary Discoveries through New Worlds, New Discoveries

Science.gov (United States)

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

2013-01-01

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

MAJOR MERGERS WITH SMALL GALAXIES: THE DISCOVERY OF A MAGELLANIC-TYPE GALAXY AT z = 0.12

International Nuclear Information System (INIS)

Koch, Andreas; Frank, Matthias J.; Pasquali, Anna; Rich, R. Michael; Rabitz, Andreas

2015-01-01

We report on the serendipitous discovery of a star-forming galaxy at redshift z = 0.116 with morphological features that indicate an ongoing merger. This object exhibits two clearly separated components with significantly different colors, plus a possible tidal stream. Follow-up spectroscopy of the bluer component revealed a low star-forming activity of 0.09 M ⊙ yr −1 and a high metallicity of 12 + log(O/H) = 8.6. Based on comparison with mass–star formation-rate and mass–metallicity relations, and on fitting of spectral energy distributions, we obtain a stellar mass of 3 × 10 9 M ⊙ , which renders this object comparable to the Large Magellanic Cloud. Thus our finding provides a further piece of evidence of a major merger already acting on small, dwarf-galaxy-like scales

MAJOR MERGERS WITH SMALL GALAXIES: THE DISCOVERY OF A MAGELLANIC-TYPE GALAXY AT z = 0.12

Energy Technology Data Exchange (ETDEWEB)

Koch, Andreas; Frank, Matthias J. [Zentrum für Astronomie der Universität Heidelberg, Landessternwarte, Königstuhl 12, D-69117 Heidelberg (Germany); Pasquali, Anna [Zentrum für Astronomie der Universität Heidelberg, Astronomisches Rechen-Institut, Mönchhofstrasse 12, D-69117 Heidelberg (Germany); Rich, R. Michael [University of California Los Angeles, Department of Physics and Astronomy, Los Angeles, CA (United States); Rabitz, Andreas, E-mail: akoch@lsw.uni-heidelberg.de [Leibniz-Institut für Astrophysik Potsdam, An der Sternwarte 16, D-14482 Potsdam (Germany)

2015-12-20

We report on the serendipitous discovery of a star-forming galaxy at redshift z = 0.116 with morphological features that indicate an ongoing merger. This object exhibits two clearly separated components with significantly different colors, plus a possible tidal stream. Follow-up spectroscopy of the bluer component revealed a low star-forming activity of 0.09 M{sub ⊙} yr{sup −1} and a high metallicity of 12 + log(O/H) = 8.6. Based on comparison with mass–star formation-rate and mass–metallicity relations, and on fitting of spectral energy distributions, we obtain a stellar mass of 3 × 10{sup 9} M{sub ⊙}, which renders this object comparable to the Large Magellanic Cloud. Thus our finding provides a further piece of evidence of a major merger already acting on small, dwarf-galaxy-like scales.

Gray matter volume and rapid decision-making in major depressive disorder.

Science.gov (United States)

Nakano, Masayuki; Matsuo, Koji; Nakashima, Mami; Matsubara, Toshio; Harada, Kenichiro; Egashira, Kazuteru; Masaki, Hiroaki; Takahashi, Kanji; Watanabe, Yoshifumi

2014-01-03

Reduced motivation and blunted decision-making are key features of major depressive disorder (MDD). Patients with MDD show abnormal decision-making when given negative feedback regarding a reward. The brain mechanisms underpinning this behavior remain unclear. In the present study, we examined the association between rapid decision-making with negative feedback and brain volume in MDD. Thirty-six patients with MDD and 54 age-, sex- and IQ-matched healthy subjects were studied. Subjects performed a rapid decision-making monetary task in which participants could make high- or low-risk choices. We compared between the 2 groups the probability that a high-risk choice followed negative feedback. In addition, we used voxel-based morphometry (VBM) to compare between group differences in gray matter volume, and the correlation between the probability for high-risk choices and brain volume. Compared to the healthy group, the MDD group showed significantly lower probabilities for high-risk choices following negative feedback. VBM analysis revealed that the MDD group had less gray matter volume in the right medial prefrontal cortex and orbitofrontal cortex (OFC) compared to the healthy group. The right OFC volume was negatively correlated with the probability that a high-risk choice followed negative feedback in patients with MDD. We did not observe these trends in healthy subjects. Patients with MDD show reduced motivation for monetary incentives when they were required to make rapid decisions following negative feedback. We observed a correlation between this reduced motivation and gray matter volume in the medial and ventral prefrontal cortex, which suggests that these brain regions are likely involved in the pathophysiology of aberrant decision-making in MDD. © 2013.

Rough – Granular Computing knowledge discovery models

Directory of Open Access Journals (Sweden)

Mohammed M. Eissa

2016-11-01

Full Text Available Medical domain has become one of the most important areas of research in order to richness huge amounts of medical information about the symptoms of diseases and how to distinguish between them to diagnose it correctly. Knowledge discovery models play vital role in refinement and mining of medical indicators to help medical experts to settle treatment decisions. This paper introduces four hybrid Rough – Granular Computing knowledge discovery models based on Rough Sets Theory, Artificial Neural Networks, Genetic Algorithm and Rough Mereology Theory. A comparative analysis of various knowledge discovery models that use different knowledge discovery techniques for data pre-processing, reduction, and data mining supports medical experts to extract the main medical indicators, to reduce the misdiagnosis rates and to improve decision-making for medical diagnosis and treatment. The proposed models utilized two medical datasets: Coronary Heart Disease dataset and Hepatitis C Virus dataset. The main purpose of this paper was to explore and evaluate the proposed models based on Granular Computing methodology for knowledge extraction according to different evaluation criteria for classification of medical datasets. Another purpose is to make enhancement in the frame of KDD processes for supervised learning using Granular Computing methodology.

The rays of life, centennial of discovery of Radium

International Nuclear Information System (INIS)

Constantin, Enrique; Plazas, Maria C.

1999-01-01

The authors make a recount from the discovery of the rays X for William Conrad Roentgen, in November of 1.985, until our days of the main discoveries and advances in medicine, having like base the radium and their importance in the treatment of the cancer

10 CFR 2.709 - Discovery against NRC staff.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Discovery against NRC staff. 2.709 Section 2.709 Energy... Rules for Formal Adjudications § 2.709 Discovery against NRC staff. (a)(1) In a proceeding in which the NRC staff is a party, the NRC staff will make available one or more witnesses, designated by the...

Proteomic and metabolomic approaches to biomarker discovery

CERN Document Server

Issaq, Haleem J

2013-01-01

Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

Donor Motivations and Decision Making: Understanding the Major Gift Development Process from a Donor's Perspective

Science.gov (United States)

Morrison, Anna Lee

2015-01-01

Higher education is faced with a challenge to its traditional funding structure. As a result, academic programs must seek alternative sources of support. Chief among these sources is philanthropy in the form of major gifts. Insight into donor motivations and decision making when approached to consider a major gift may help to maximize the success…

Causality discovery technology

Science.gov (United States)

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

2012-11-01

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

Mathematical modeling for novel cancer drug discovery and development.

Science.gov (United States)

Zhang, Ping; Brusic, Vladimir

2014-10-01

Mathematical modeling enables: the in silico classification of cancers, the prediction of disease outcomes, optimization of therapy, identification of promising drug targets and prediction of resistance to anticancer drugs. In silico pre-screened drug targets can be validated by a small number of carefully selected experiments. This review discusses the basics of mathematical modeling in cancer drug discovery and development. The topics include in silico discovery of novel molecular drug targets, optimization of immunotherapies, personalized medicine and guiding preclinical and clinical trials. Breast cancer has been used to demonstrate the applications of mathematical modeling in cancer diagnostics, the identification of high-risk population, cancer screening strategies, prediction of tumor growth and guiding cancer treatment. Mathematical models are the key components of the toolkit used in the fight against cancer. The combinatorial complexity of new drugs discovery is enormous, making systematic drug discovery, by experimentation, alone difficult if not impossible. The biggest challenges include seamless integration of growing data, information and knowledge, and making them available for a multiplicity of analyses. Mathematical models are essential for bringing cancer drug discovery into the era of Omics, Big Data and personalized medicine.

A New Universe of Discoveries

Science.gov (United States)

Córdova, France A.

2016-01-01

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

Effective Online Group Discovery in Trajectory Databases

DEFF Research Database (Denmark)

Li, Xiaohui; Ceikute, Vaida; Jensen, Christian S.

2013-01-01

GPS-enabled devices are pervasive nowadays. Finding movement patterns in trajectory data stream is gaining in importance. We propose a group discovery framework that aims to efficiently support the online discovery of moving objects that travel together. The framework adopts a sampling-independen......GPS-enabled devices are pervasive nowadays. Finding movement patterns in trajectory data stream is gaining in importance. We propose a group discovery framework that aims to efficiently support the online discovery of moving objects that travel together. The framework adopts a sampling......-independent approach that makes no assumptions about when positions are sampled, gives no special importance to sampling points, and naturally supports the use of approximate trajectories. The framework's algorithms exploit state-of-the-art, density-based clustering (DBScan) to identify groups. The groups are scored...

The discovery of subatomic particles

International Nuclear Information System (INIS)

Weinberg, S.

1984-01-01

This book developed from a course for students with no prior training in mathematics of physics to learn about the achievements of 20th century physics and classical physics. It covers the discovery of fundamental particles of ordinary atoms: the electron, the proton, and the neutron. The general outline is historical and it is for readers unfamiliar with classical physics who wish to understand the ideas and experiments that make up the history of 20th century physics. Contents include: A world of particles, the discovery of the electron, the atomic scale, the nucleus, more particles

Scientific Discoveries: What Is Required for Lasting Impact.

Science.gov (United States)

Lømo, Terje

2016-01-01

I have been involved in two scientific discoveries of some impact. One is the discovery of long-term potentiation (LTP), the phenomenon that brief, high-frequency impulse activity at synapses in the brain can lead to long-lasting increases in their efficiency of transmission. This finding demonstrated that synapses are plastic, a property thought to be necessary for learning and memory. The other discovery is that nerve-evoked muscle impulse activity, rather than putative trophic factors, controls the properties of muscle fibers. Here I describe how these two discoveries were made, the unexpected difficulties of reproducing the first discovery, and the controversies that followed the second discovery. I discuss why the first discovery took many years to become generally recognized, whereas the second caused an immediate sensation and entered textbooks and major reviews but is now largely forgotten. In the long run, discovering a new phenomenon has greater impact than falsifying a popular hypothesis.

Story of Superconductivity: A Serendipitous Discovery

Indian Academy of Sciences (India)

, offered a glimmerof hope to make this dream possible. It was a discoverytotally unexpected at that time, and we owe this discovery tothe painstaking andmethodical investigations of Onnes – firstto produce very low temperatures, and then ...

Verifying Galileo's discoveries: telescope-making at the Collegio Romano

Science.gov (United States)

Reeves, Eileen; van Helden, Albert

The Jesuits of the Collegio Romano in Rome, especially the mathematicians Clavius and Grienberger, were very interested in Galilei's discoveries. After they had failed to recognize with telescopes of own construction the celestial phenomena, they expressed serious doubts. But from November 1610 onward, after they had built a better telescope and had obtained from Venice another one in addition, and could verify Galilei's observations, they completely accepted them. Clavius, who stuck to the Ptolemaic system till his death in 1612, even pointed out these facts in his last edition of Sacrobosco's Sphaera. He as well as his conpatres, however, avoided any conclusions with respect to the planetary system.

A Technique Socratic Questioning-Guided Discovery

Directory of Open Access Journals (Sweden)

M. Hakan Türkçapar

2012-03-01

Full Text Available “Socratic Method” is a way of teaching philosophical thinking and knowledge by asking questions which was used by antique period greek philosopher Socrates. Socrates was teaching knowledge to his followers by asking questions and the conversation between them was named “Socratic Dialogues”. In this meaning, no novel knowledge is taught to the individual but only what is formerly known is reminded and rediscovered. The form of socratic questioning which is used during the process of cognitive behavioral therapy is known as Guided Discovery. In this method it is aimed to make the client notice the piece of knowledge which he could notice but is not aware with a series of questions. Socratic method or guided discovery consists of several steps which are: Identifying the problem by listening to the client and making reflections, finding alternatives by examining and evaluating, reidentification by using the newly found information and questioning the old distorted belief and reaching to a conclusion and applying it. Question types used during these procedures are, questions for gaining information, questions revealing the meanings, questions revealing the beliefs, questions about behaviours during the similar past experiences, analyse questions and analytic synthesis questions. In order to make the patient feel understood it is important to be empathetic and summarising the problem during the interview. In this text, steps of Socratic Questioning-Guided Discovery will be reviewed with sample dialogues after each step

Privacy and User Experience in 21st Century Library Discovery

Directory of Open Access Journals (Sweden)

Shayna Pekala

2017-06-01

Full Text Available Over the last decade, libraries have taken advantage of emerging technologies to provide new discovery tools to help users find information and resources more efficiently. In the wake of this technological shift in discovery, privacy has become an increasingly prominent and complex issue for libraries. The nature of the web, over which users interact with discovery tools, has substantially diminished the library’s ability to control patron privacy. The emergence of a data economy has led to a new wave of online tracking and surveillance, in which multiple third parties collect and share user data during the discovery process, making it much more difficult, if not impossible, for libraries to protect patron privacy. In addition, users are increasingly starting their searches with web search engines, diminishing the library’s control over privacy even further. While libraries have a legal and ethical responsibility to protect patron privacy, they are simultaneously challenged to meet evolving user needs for discovery. In a world where “search” is synonymous with Google, users increasingly expect their library discovery experience to mimic their experience using web search engines. However, web search engines rely on a drastically different set of privacy standards, as they strive to create tailored, personalized search results based on user data. Libraries are seemingly forced to make a choice between delivering the discovery experience users expect and protecting user privacy. This paper explores the competing interests of privacy and user experience, and proposes possible strategies to address them in the future design of library discovery tools.

Guided Discovery with Socratic Questioning

Directory of Open Access Journals (Sweden)

M. Hakan Türkçapar

2015-04-01

Full Text Available “The Socratic method” is a way of teaching philosophical thinking and knowledge by asking questions. It was first used by in ancient times by the Greek philosopher Socrates who taught his followers by asking questions; these conversations between them are known as “Socratic dialogues”. In this methodology, no new knowledge is taught to the individual; rather, the individual is guided to remember and rediscover what was formerly known through this process. The main method used in cognitive therapy is guided discovery. There are various methods of guided discovery in cognitive therapy. The form of verbal exchange between the therapist and client which is used during the process of cognitive behavioral therapy is known as “socratic questioning”. In this method the goal is to make the client rediscover, with a series of questions, a piece of knowledge which he could otherwise know but is not presently conscious of. The Socratic Questioning consists of several steps, including: identifying the problem by listening to the client and making reflections, finding alternatives by examining and evaluating, reidentification by using the newly rediscovered information and questioning the old distorted belief, and reaching a new conclusion and applying it. Question types used during these procedures are: questions for collecting information, questions revealing meanings, questions revealing beliefs, questions about behaviours during similar past experiences, analytic questions and analytic synthesis questions. In order to make the patient feel understood, it is important to be empathetic and summarize the problem during the interview. In this text, steps of Socratic Questioning-Guided Discovery will be reviewed with sample dialogues provided for each step. [JCBPR 2015; 4(1.000: 47-53

Impact of New Camera Technologies on Discoveries in Cell Biology.

Science.gov (United States)

Stuurman, Nico; Vale, Ronald D

2016-08-01

New technologies can make previously invisible phenomena visible. Nowhere is this more obvious than in the field of light microscopy. Beginning with the observation of "animalcules" by Antonie van Leeuwenhoek, when he figured out how to achieve high magnification by shaping lenses, microscopy has advanced to this day by a continued march of discoveries driven by technical innovations. Recent advances in single-molecule-based technologies have achieved unprecedented resolution, and were the basis of the Nobel prize in Chemistry in 2014. In this article, we focus on developments in camera technologies and associated image processing that have been a major driver of technical innovations in light microscopy. We describe five types of developments in camera technology: video-based analog contrast enhancement, charge-coupled devices (CCDs), intensified sensors, electron multiplying gain, and scientific complementary metal-oxide-semiconductor cameras, which, together, have had major impacts in light microscopy. © 2016 Marine Biological Laboratory.

Discovery of a transiting planet near the snow-line

International Nuclear Information System (INIS)

Kipping, D. M.; Torres, G.; Buchhave, L. A.; Kenyon, S. J.; Henze, C.; Bryson, S. T.; Isaacson, H.; Kolbl, R.; Marcy, G. W.; Stassun, K.; Bastien, F.

2014-01-01

In most theories of planet formation, the snow-line represents a boundary between the emergence of the interior rocky planets and the exterior ice giants. The wide separation of the snow-line makes the discovery of transiting worlds challenging, yet transits would allow for detailed subsequent characterization. We present the discovery of Kepler-421b, a Uranus-sized exoplanet transiting a G9/K0 dwarf once every 704.2 days in a near-circular orbit. Using public Kepler photometry, we demonstrate that the two observed transits can be uniquely attributed to the 704.2 day period. Detailed light curve analysis with BLENDER validates the planetary nature of Kepler-421b to >4σ confidence. Kepler-421b receives the same insolation as a body at ∼2 AU in the solar system, as well as a Uranian albedo, which would have an effective temperature of ∼180 K. Using a time-dependent model for the protoplanetary disk, we estimate that Kepler-421b's present semi-major axis was beyond the snow-line after ∼3 Myr, indicating that Kepler-421b may have formed at its observed location.

Discovery of a transiting planet near the snow-line

Energy Technology Data Exchange (ETDEWEB)

Kipping, D. M.; Torres, G.; Buchhave, L. A.; Kenyon, S. J. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Henze, C.; Bryson, S. T. [NASA Ames Research Center, Moffett Field, CA 94035 (United States); Isaacson, H.; Kolbl, R.; Marcy, G. W. [University of California, Berkeley, CA 94720 (United States); Stassun, K. [Department of Physics and Astronomy, Vanderbilt University, 1807 Station B, Nashville, TN 37235 (United States); Bastien, F., E-mail: dkipping@cfa.harvard.edu [Physics Department, Fisk University, 1000 17th Ave. N, Nashville, TN 37208 (United States)

2014-11-01

In most theories of planet formation, the snow-line represents a boundary between the emergence of the interior rocky planets and the exterior ice giants. The wide separation of the snow-line makes the discovery of transiting worlds challenging, yet transits would allow for detailed subsequent characterization. We present the discovery of Kepler-421b, a Uranus-sized exoplanet transiting a G9/K0 dwarf once every 704.2 days in a near-circular orbit. Using public Kepler photometry, we demonstrate that the two observed transits can be uniquely attributed to the 704.2 day period. Detailed light curve analysis with BLENDER validates the planetary nature of Kepler-421b to >4σ confidence. Kepler-421b receives the same insolation as a body at ∼2 AU in the solar system, as well as a Uranian albedo, which would have an effective temperature of ∼180 K. Using a time-dependent model for the protoplanetary disk, we estimate that Kepler-421b's present semi-major axis was beyond the snow-line after ∼3 Myr, indicating that Kepler-421b may have formed at its observed location.

A study on the major influencing factors in decision-making in abnormal radiological situations

International Nuclear Information System (INIS)

Kang, B. W.; Kim, S. K.

2001-01-01

This paper describes the task of the technical advisers within the off-site emergency response organization in nuclear accident. They shall be collected and evaluated all influencing factors relevant in decision-making process. The major influencing objective factors are the results of radiological and economic consequence assessments. However, it is associated with uncertainties in predictions dependent of the phase of the accident. Important other factors emerge from subjective arguments between technical advisers in decision-making process. By theirs different opinions, the decision maker who is lack of experience and knowledge has a much more difficult to make and implement the emergency actions. Therefore, the practically considerations in a concrete emergency situation are timely implemented the emergency actions result from already existing plans. The actual process of decision-making consists in identifying in a iterative process implementing individual actions or a set of combined action

Students Use VLA to Make Startling Brown-Dwarf Discovery

Science.gov (United States)

2001-03-01

A group of summer students making a long-shot astronomical gamble with the National Science Foundation's (NSF) Very Large Array (VLA) have found the first radio emission ever detected from a brown dwarf, an enigmatic object that is neither a star nor a planet, but something in between. Their surprising discovery is forcing experts to re-think their theories about how brown dwarfs work. The Very Large Array "Many astronomers are surprised at this discovery, because they didn't expect such strong radio emission from this object," said Shri Kulkarni, a Caltech professor who was on the team that first discovered a brown dwarf in 1995, and advisor to one of the students. "What is so cool is that this is research that probably nobody else would have tried to do because of its low chance of success. That made it ideal for summer students -- we had almost nothing to lose," said Kate Becker, a student at Oberlin College in Ohio. "The radio emission these students discovered coming from this brown dwarf is 10,000 times stronger than anyone expected," said Dale Frail, an astronomer at the National Radio Astronomy Observatory (NRAO) in Socorro, NM. "This student project is going to open up a whole new area of research for the VLA," Frail added. The students, in addition to Becker, are: Edo Berger from Caltech; Steven Ball from New Mexico Tech in Socorro, NM; Melanie Clarke from Carleton College in Northfield, MN; Therese Fukuda from the University of Denver; Ian Hoffman from the University of New Mexico in Albuquerque; Richard Mellon from The Pennsylvania State University; Emmanuel Momjian from the University of Kentucky; Nathanial Murphy from Amherst College in Amherst, MA; Stacey Teng from the University of Maryland; Timothy Woodruff from Southwestern University in Georgetown, TX; Ashley Zauderer from Agnes Scott College in Decatur, GA; and Robert Zavala from New Mexico State University in Las Cruces, NM. Frail also is an author of the research paper, published in the March

Advanced biological and chemical discovery (ABCD): centralizing discovery knowledge in an inherently decentralized world.

Science.gov (United States)

Agrafiotis, Dimitris K; Alex, Simson; Dai, Heng; Derkinderen, An; Farnum, Michael; Gates, Peter; Izrailev, Sergei; Jaeger, Edward P; Konstant, Paul; Leung, Albert; Lobanov, Victor S; Marichal, Patrick; Martin, Douglas; Rassokhin, Dmitrii N; Shemanarev, Maxim; Skalkin, Andrew; Stong, John; Tabruyn, Tom; Vermeiren, Marleen; Wan, Jackson; Xu, Xiang Yang; Yao, Xiang

2007-01-01

We present ABCD, an integrated drug discovery informatics platform developed at Johnson & Johnson Pharmaceutical Research & Development, L.L.C. ABCD is an attempt to bridge multiple continents, data systems, and cultures using modern information technology and to provide scientists with tools that allow them to analyze multifactorial SAR and make informed, data-driven decisions. The system consists of three major components: (1) a data warehouse, which combines data from multiple chemical and pharmacological transactional databases, designed for supreme query performance; (2) a state-of-the-art application suite, which facilitates data upload, retrieval, mining, and reporting, and (3) a workspace, which facilitates collaboration and data sharing by allowing users to share queries, templates, results, and reports across project teams, campuses, and other organizational units. Chemical intelligence, performance, and analytical sophistication lie at the heart of the new system, which was developed entirely in-house. ABCD is used routinely by more than 1000 scientists around the world and is rapidly expanding into other functional areas within the J&J organization.

The discovery of the tau lepton

International Nuclear Information System (INIS)

Perl, M.L.

1992-09-01

The discovery of the tau lepton and the third generation of fermions came from the convergence of three physics streams in the late 1960's and early 1970's. These streams were: the failed attempts by myself and others to understand the connection between the electron and the muon, the development of electron-positron storage rings, and the development of the theory of sequential leptons. In this paper I give the history of the discovery of the tau and the measurement of its major properties-the properties which established the tau as a sequential lepton

The Discovery of the Double Helix

CERN Multimedia

CERN. Geneva

2011-01-01

Professor James D. Watson has kindly agreed to make a presentation on the 1953 finding of the Double Helix at the Cavendish Laboratory by Francis Crick and himself. Being one of the greatest scientific discoveries in human history, little else needs to be added.

A collaborative filtering-based approach to biomedical knowledge discovery.

Science.gov (United States)

Lever, Jake; Gakkhar, Sitanshu; Gottlieb, Michael; Rashnavadi, Tahereh; Lin, Santina; Siu, Celia; Smith, Maia; Jones, Martin R; Krzywinski, Martin; Jones, Steven J M; Wren, Jonathan

2018-02-15

The increase in publication rates makes it challenging for an individual researcher to stay abreast of all relevant research in order to find novel research hypotheses. Literature-based discovery methods make use of knowledge graphs built using text mining and can infer future associations between biomedical concepts that will likely occur in new publications. These predictions are a valuable resource for researchers to explore a research topic. Current methods for prediction are based on the local structure of the knowledge graph. A method that uses global knowledge from across the knowledge graph needs to be developed in order to make knowledge discovery a frequently used tool by researchers. We propose an approach based on the singular value decomposition (SVD) that is able to combine data from across the knowledge graph through a reduced representation. Using cooccurrence data extracted from published literature, we show that SVD performs better than the leading methods for scoring discoveries. We also show the diminishing predictive power of knowledge discovery as we compare our predictions with real associations that appear further into the future. Finally, we examine the strengths and weaknesses of the SVD approach against another well-performing system using several predicted associations. All code and results files for this analysis can be accessed at https://github.com/jakelever/knowledgediscovery. sjones@bcgsc.ca. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Social-economical decision making in current and remitted major depression.

Science.gov (United States)

Pulcu, E; Thomas, E J; Trotter, P D; McFarquhar, M; Juhasz, G; Sahakian, B J; Deakin, J F W; Anderson, I M; Zahn, R; Elliott, R

2015-04-01

Prosocial emotions related to self-blame are important in guiding human altruistic decisions. These emotions are elevated in major depressive disorder (MDD), such that MDD has been associated with guilt-driven pathological hyper-altruism. However, the impact of such emotional impairments in MDD on different types of social decision-making is unknown. In order to address this issue, we investigated different kinds of altruistic behaviour (interpersonal cooperation and fund allocation, altruistic punishment and charitable donation) in 33 healthy subjects, 35 patients in full remission (unmedicated) and 24 currently depressed patients (11 on medication) using behavioural-economical paradigms. We show a significant main effect of clinical status on altruistic decisions (p = 0.04) and a significant interaction between clinical status and type of altruistic decisions (p = 0.03). More specifically, symptomatic patients defected significantly more in the Prisoner's Dilemma game (p guilt elicited by receiving unfair financial offers in the Ultimatum Game (p guilt-driven pathological hyper-altruism hypothesis in depression. There were also differences in both current and remitted patients in the relationship between altruistic behaviour and pathological self-blaming, suggesting an important role for these emotions in moral and social decision-making abnormalities in depression.

Sea Level Rise Data Discovery

Science.gov (United States)

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

2016-12-01

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

Rule Induction-Based Knowledge Discovery for Energy Efficiency

OpenAIRE

Chen, Qipeng; Fan, Zhong; Kaleshi, Dritan; Armour, Simon M D

2015-01-01

Rule induction is a practical approach to knowledge discovery. Provided that a problem is developed, rule induction is able to return the knowledge that addresses the goal of this problem as if-then rules. The primary goals of knowledge discovery are for prediction and description. The rule format knowledge representation is easily understandable so as to enable users to make decisions. This paper presents the potential of rule induction for energy efficiency. In particular, three rule induct...

Making Sense of Turmoil: How Women Reconcile Their Emotional Response to Discovery of a Potential Breast Cancer Symptom.

Science.gov (United States)

O'Mahony, Máirín; Hegarty, Josephine; Rooney, Vivien M

2017-11-07

Breast cancer continues to be a major public health problem for women. Early detection and treatment are key to improved outcomes. Whereas most women seek help promptly, some postpone seeking help for self-discovered breast symptoms. Investigation of women's help-seeking behavior and the associated influencing factors on self-discovery of a breast symptom were sought. The aim of this article is to report the qualitative data from women who had self-discovered a breast symptom. Women (n = 167) with a self-discovered breast symptom (who were part of a large quantitative correlational study) commented in an open-ended question on their overall experience. Comments were analyzed using Discourse Analysis. Four linked discourses were identified: (1) "being and remaining normal," (2) "emotion," (3) "becoming and being abnormal," and (4) "rationality." A sidelined discourse of emotion is drawn on to defer taking action based on rational knowledge. The tension between discourses "emotion" and "rationality" further informs our understanding of women's help-seeking behavior following self-discovered symptoms. Findings provide a deeper understanding of the emotional aspects of women's experience around symptom discovery. Findings will be of benefit to all healthcare professionals involved in assessment and screening of breast changes suggestive of breast cancer. They provide a novel insight into the meaning of breast cancer, its diagnosis and treatment, and how this impacts women's emotions as they await consultation in a breast clinic.

Discovery of resources using MADM approaches for parallel and distributed computing

Directory of Open Access Journals (Sweden)

Mandeep Kaur

2017-06-01

Full Text Available Grid, a form of parallel and distributed computing, allows the sharing of data and computational resources among its users from various geographical locations. The grid resources are diverse in terms of their underlying attributes. The majority of the state-of-the-art resource discovery techniques rely on the static resource attributes during resource selection. However, the matching resources based on the static resource attributes may not be the most appropriate resources for the execution of user applications because they may have heavy job loads, less storage space or less working memory (RAM. Hence, there is a need to consider the current state of the resources in order to find the most suitable resources. In this paper, we have proposed a two-phased multi-attribute decision making (MADM approach for discovery of grid resources by using P2P formalism. The proposed approach considers multiple resource attributes for decision making of resource selection and provides the best suitable resource(s to grid users. The first phase describes a mechanism to discover all matching resources and applies SAW method to shortlist the top ranked resources, which are communicated to the requesting super-peer. The second phase of our proposed methodology applies integrated MADM approach (AHP enriched PROMETHEE-II on the list of selected resources received from different super-peers. The pairwise comparison of the resources with respect to their attributes is made and the rank of each resource is determined. The top ranked resource is then communicated to the grid user by the grid scheduler. Our proposed methodology enables the grid scheduler to allocate the most suitable resource to the user application and also reduces the search complexity by filtering out the less suitable resources during resource discovery.

Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.

Science.gov (United States)

Verbist, Bie; Klambauer, Günter; Vervoort, Liesbet; Talloen, Willem; Shkedy, Ziv; Thas, Olivier; Bender, Andreas; Göhlmann, Hinrich W H; Hochreiter, Sepp

2015-05-01

The pharmaceutical industry is faced with steadily declining R&D efficiency which results in fewer drugs reaching the market despite increased investment. A major cause for this low efficiency is the failure of drug candidates in late-stage development owing to safety issues or previously undiscovered side-effects. We analyzed to what extent gene expression data can help to de-risk drug development in early phases by detecting the biological effects of compounds across disease areas, targets and scaffolds. For eight drug discovery projects within a global pharmaceutical company, gene expression data were informative and able to support go/no-go decisions. Our studies show that gene expression profiling can detect adverse effects of compounds, and is a valuable tool in early-stage drug discovery decision making. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Making the Long Tail Visible: Social Networking Sites and Independent Music Discovery

Science.gov (United States)

Gaffney, Michael; Rafferty, Pauline

2009-01-01

Purpose: The purpose of this paper is to investigate users' knowledge and use of social networking sites and folksonomies to discover if social tagging and folksonomies, within the area of independent music, aid in its information retrieval and discovery. The sites examined in this project are MySpace, Lastfm, Pandora and Allmusic. In addition,…

Informed decision-making in elective major vascular surgery: analysis of 145 surgeon-patient consultations.

Science.gov (United States)

Etchells, Edward; Ferrari, Michel; Kiss, Alex; Martyn, Nikki; Zinman, Deborah; Levinson, Wendy

2011-06-01

Prior studies show significant gaps in the informed decision-making process, a central goal of surgical care. These studies have been limited by their focus on low-risk decisions, single visits rather than entire consultations, or both. Our objectives were, first, to rate informed decision-making for major elective vascular surgery based on audiotapes of actual physician-patient conversations and, second, to compare ratings of informed decision-making for first visits to ratings for multiple visits by the same patient over time. We prospectively enrolled patients for whom vascular surgical treatment was a potential option at a tertiary care outpatient vascular surgery clinic. We audio-taped all surgeon-patient conversations, including multiple visits when necessary, until a decision was made. Using an existing method, we evaluated the transcripts for elements of decision-making, including basic elements (e.g., an explanation of the clinical condition), intermediate elements (e.g., risks and benefits) and complex elements (e.g., uncertainty around the decision). We analyzed 145 surgeon-patient consultations. Overall, 45% of consultations contained complex elements, whereas 23% did not contain the basic elements of decision-making. For the 67 consultations that involved multiple visits, ratings were significantly higher when evaluating all visits (50% complex elements) compared with evaluating only the first visit (33% complex elements, p decision-making over multiple visits yielded different results than analyzing decision-making for single visits.

Impaired social decision making in patients with major depressive disorder.

Science.gov (United States)

Zhang, Hui-Jun; Sun, Delin; Lee, Tatia M C

2012-07-01

Research on how depression influences social decision making has been scarce. This study investigated how people with depression make decisions in an interpersonal trust-reciprocity game. Fifty female patients diagnosed with major depressive disorders (MDDs) and 49 healthy women participated in this study. The experiment was conducted on a one-to-one basis. Participants were asked to play the role of a trustee responsible for investing money given to them by an anonymous female investor playing on another computer station. In each trial, the investor would send to a participant (the trustee) a request for a certain percentage of the appreciated investment (repayment proportion). Since only the participant knew the exact amount of the appreciated investment, she could decide to pay more (altruistic act), the same, or less (deceptive act) than the requested amount. The participant's money acquired in the trial would be confiscated if her deceptive act was caught. The frequency of deceptive or altruistic decisions and relative monetary gain in each decision choice were examined. People with depression made fewer deceptive and fewer altruistic responses than healthy controls in all conditions. Moreover, the specific behavioral pattern presented by people with depression was modulated by the task factors, including the risk of deception detection and others' intentions (benevolence vs. malevolence). Findings of this study contribute to furthering our understanding of the specific pattern of social behavioral changes associated with depression.

Drug discovery and developments in developing countries ...

African Journals Online (AJOL)

the major burden being in developing countries. Many of ... The driving force for drug discovery and development by pharmaceutical firms ... world and particularly in the third world countries ..... GFHR (2000) Global Forum for Health Research:.

Advances in Chance Discovery : Extended Selection from International Workshops

CERN Document Server

Abe, Akinori

2013-01-01

Since year 2000, scientists on artificial and natural intelligences started to study chance discovery - methods for discovering events/situations that significantly affect decision making. Partially because the editors Ohsawa and Abe are teaching at schools of Engineering and of Literature with sharing the interest in chance discovery, this book reflects interdisciplinary aspects of progress: First, as an interdisciplinary melting pot of cognitive science, computational intelligence, data mining/visualization, collective intelligence, … etc, chance discovery came to reach new application domains e.g. health care, aircraft control, energy plant, management of technologies, product designs, innovations, marketing, finance etc. Second, basic technologies and sciences including sensor technologies, medical sciences, communication technologies etc. joined this field and interacted with cognitive/computational scientists in workshops on chance discovery, to obtain breakthroughs by stimulating each other. Third, �...

The "Make Your Own Religion" Project

Science.gov (United States)

Bauman, Chad M.; Hege, Brent A. R.; Kleckley, Russell; Willsky-Ciollo, Lydia; Lopez, Davina C.

2016-01-01

The "Make Your Own Religion" class project was designed to address a perceived need to introduce more theoretical thinking about religion into a typical religion survey course, and to do so in such a way that students would experience the wonder of theoretical discovery, and through or because of that discovery hopefully both better…

Discovery Mondays

CERN Multimedia

2003-01-01

Many people don't realise quite how much is going on at CERN. Would you like to gain first-hand knowledge of CERN's scientific and technological activities and their many applications? Try out some experiments for yourself, or pick the brains of the people in charge? If so, then the «Lundis Découverte» or Discovery Mondays, will be right up your street. Starting on May 5th, on every first Monday of the month you will be introduced to a different facet of the Laboratory. CERN staff, non-scientists, and members of the general public, everyone is welcome. So tell your friends and neighbours and make sure you don't miss this opportunity to satisfy your curiosity and enjoy yourself at the same time. You won't have to listen to a lecture, as the idea is to have open exchange with the expert in question and for each subject to be illustrated with experiments and demonstrations. There's no need to book, as Microcosm, CERN's interactive museum, will be open non-stop from 7.30 p.m. to 9 p.m. On the first Discovery M...

Mass spectrometry for protein quantification in biomarker discovery.

Science.gov (United States)

Wang, Mu; You, Jinsam

2012-01-01

Major technological advances have made proteomics an extremely active field for biomarker discovery in recent years due primarily to the development of newer mass spectrometric technologies and the explosion in genomic and protein bioinformatics. This leads to an increased emphasis on larger scale, faster, and more efficient methods for detecting protein biomarkers in human tissues, cells, and biofluids. Most current proteomic methodologies for biomarker discovery, however, are not highly automated and are generally labor-intensive and expensive. More automation and improved software programs capable of handling a large amount of data are essential to reduce the cost of discovery and to increase throughput. In this chapter, we discuss and describe mass spectrometry-based proteomic methods for quantitative protein analysis.

Queen's discovery lauded by top scientific journal

CERN Multimedia

McGrady, S

2002-01-01

A scientific breakthrough at Queen's University's Sudbury Neutrino Observatory has received major international recognition. The journal Science ranked the discovery that cracked the "neutrino problem" second, in the journal's top 10 scientific achievements of 2002 (1/2 page).

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

Science.gov (United States)

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.

On the threshold of discovery

International Nuclear Information System (INIS)

Cherenkov, P.A.

1986-01-01

The author, the discoverer of the Cherenkov radiation, recalls some interesting circumstances of his discoery 50 years ago and puts it into the context of the knowledge of the period. The discovery of Cherenkov radiation which today is in practice used especially for the detection of charged particles, was correctly understood and appreciated somewhat belatedly. At first the discovery was met with distrust and the original article announcing it was rejected by the magazine Nature. In effect, the discovery was not the result of any planned experiment but was the by-product of another research. It was, of course, allowed by previous achievements in various fields of physics, namely progress reached in the study of luminescence by S.I. Vavilov and his pupils. The discovery was made during an experimental study of luminescence induced in liquids by the β and γ radiations of uranyl salts. During his attempts to suppress the background radiation from vessel walls the autor found a ''background'' from pure solvent which differed from luminescence by being independent of the concentration, temperature and viscosity of the liquid. A closer examination of the phenomenon more or less by accident revealed its marked spatial asymmetry which had major importance for the development of the theory of the new phenomenon by I.V. Tamm and I.M. Frank. (A.K.)

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

Science.gov (United States)

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.

ACTS/TOS after release from Shuttle Discovery

Science.gov (United States)

1993-01-01

The Advanced Communications Technology Satellite (ACTS) with its Transfer Orbit Stage (TOS) is backdropped over the blue ocean following its release from the Earth-orbiting Space Shuttle Discovery. ACTS/TOS deploy was the first major task performed on the almost ten-day mission.

Perspectives of biomolecular NMR in drug discovery: the blessing and curse of versatility

International Nuclear Information System (INIS)

Jahnke, Wolfgang

2007-01-01

The versatility of NMR and its broad applicability to several stages in the drug discovery process is well known and generally considered one of the major strengths of NMR (Pellecchia et al., Nature Rev Drug Discov 1:211-219, 2002; Stockman and Dalvit, Prog Nucl Magn Reson Spectrosc 41:187-231, 2002; Lepre et al., Comb Chem High throughput screen 5:583-590, 2002; Wyss et al., Curr Opin Drug Discov Devel 5:630-647, 2002; Jahnke and Widmer, Cell Mol Life Sci 61:580-599, 2004; Huth et al., Methods Enzymol 394:549-571, 2005b; Klages et al., Mol Biosyst 2:318-332, 2006; Takeuchi and Wagner, Curr Opin Struct Biol 16:109-117, 2006; Zartler and Shapiro, Curr Pharm Des 12:3963-3972, 2006). Indeed, NMR is the only biophysical technique which can detect and quantify molecular interactions, and at the same time provide detailed structural information with atomic level resolution. NMR should therefore be ideally suited and widely requested as a tool for drug discovery research, and numerous examples of drug discovery projects which have substantially benefited from NMR contributions or were even driven by NMR have been described in the literature. However, not all pharmaceutical companies have rigorously implemented NMR as integral tool of their research processes. Some companies invest with limited resources, and others do not use biomolecular NMR at all. This discrepancy in assessing the value of a technology is striking, and calls for clarification-under which circumstances can NMR provide added value to the drug discovery process? What kind of contributions can NMR make, and how is it implemented and integrated for maximum impact? This perspectives article suggests key areas of impact for NMR, and a model of integrating NMR with other technologies to realize synergies and maximize their value for drug discovery

Using the domain identification model to study major and career decision-making processes

Science.gov (United States)

Tendhar, Chosang; Singh, Kusum; Jones, Brett D.

2018-03-01

The purpose of this study was to examine the extent to which (1) a domain identification model could be used to predict students' engineering major and career intentions and (2) the MUSIC Model of Motivation components could be used to predict domain identification. The data for this study were collected from first-year engineering students. We used a structural equation model to test the hypothesised relationship between variables in the partial domain identification model. The findings suggested that engineering identification significantly predicted engineering major intentions and career intentions and had the highest effect on those two variables compared to other motivational constructs. Furthermore, results suggested that success, interest, and caring are plausible contributors to students' engineering identification. Overall, there is strong evidence that the domain identification model can be used as a lens to study career decision-making processes in engineering, and potentially, in other fields as well.

Effects of Computer-Assisted Instruction in Using Formal Decision-Making Strategies to Choose a College Major.

Science.gov (United States)

Mau, Wei-Cheng; Jepsen, David A.

1992-01-01

Compared decision-making strategies and college major choice among 113 first-year students assigned to Elimination by Aspects Strategy (EBA), Subjective Expected Utility Strategy (SEU), and control groups. "Rational" EBA students scored significantly higher on choice certainty; lower on choice anxiety and career indecision than "rational"…

389 Effect of Guided-Discovery, Student- Centred Demonstration ...

African Journals Online (AJOL)

User

2010-10-16

Oct 16, 2010 ... chemistry teachers in secondary schools make effective use of guided- discovery and ... Educationist and educational psychologist have made earnest effort at developing ..... Njoku, Z. C. (2009), Teaching Chemistry using Science, Technology and ... primary school teaching and learning. Journal of ...

Volatility Discovery

DEFF Research Database (Denmark)

Dias, Gustavo Fruet; Scherrer, Cristina; Papailias, Fotis

The price discovery literature investigates how homogenous securities traded on different markets incorporate information into prices. We take this literature one step further and investigate how these markets contribute to stochastic volatility (volatility discovery). We formally show...... that the realized measures from homogenous securities share a fractional stochastic trend, which is a combination of the price and volatility discovery measures. Furthermore, we show that volatility discovery is associated with the way that market participants process information arrival (market sensitivity......). Finally, we compute volatility discovery for 30 actively traded stocks in the U.S. and report that Nyse and Arca dominate Nasdaq....

Microbial genome mining for accelerated natural products discovery: is a renaissance in the making?

Science.gov (United States)

Bachmann, Brian O; Van Lanen, Steven G; Baltz, Richard H

2014-02-01

Microbial genome mining is a rapidly developing approach to discover new and novel secondary metabolites for drug discovery. Many advances have been made in the past decade to facilitate genome mining, and these are reviewed in this Special Issue of the Journal of Industrial Microbiology and Biotechnology. In this Introductory Review, we discuss the concept of genome mining and why it is important for the revitalization of natural product discovery; what microbes show the most promise for focused genome mining; how microbial genomes can be mined; how genome mining can be leveraged with other technologies; how progress on genome mining can be accelerated; and who should fund future progress in this promising field. We direct interested readers to more focused reviews on the individual topics in this Special Issue for more detailed summaries on the current state-of-the-art.

The asymmetry between discoveries and inventions in the Nobel Prize for Physics

NARCIS (Netherlands)

Bartneck, C.; Rauterberg, G.W.M.

2008-01-01

This paper presents an empirical study on the frequency of discoveries and inventions that were awarded with the. More than 70 per cent of all Nobel Prizes were given to discoveries. The majority of inventions were awarded at the beginning of the twentieth century and only three inventions had a

The discovery and measurements of a Higgs boson.

Science.gov (United States)

Gianotti, F; Virdee, T S

2015-01-13

In July 2012, the ATLAS and CMS collaborations at CERN's Large Hadron Collider announced the discovery of a Higgs-like boson, a new heavy particle at a mass more than 130 times the mass of a proton. Since then, further data have revealed its properties to be strikingly similar to those of the Standard Model Higgs boson, a particle expected from the mechanism introduced almost 50 years ago by six theoreticians including British physicists Peter Higgs from Edinburgh University and Tom Kibble from Imperial College London. The discovery is the culmination of a truly remarkable scientific journey and undoubtedly the most significant scientific discovery of the twenty-first century so far. Its experimental confirmation turned out to be a monumental task requiring the creation of an accelerator and experiments of unprecedented capability and complexity, designed to discern the signatures that correspond to the Higgs boson. Thousands of scientists and engineers, in each of the ATLAS and CMS teams, came together from all four corners of the world to make this massive discovery possible.

Major depression in primary care: making the diagnosis

Science.gov (United States)

Ng, Chung Wai Mark; How, Choon How; Ng, Yin Ping

2016-01-01

Major depression is a common condition seen in the primary care setting, often presenting with somatic symptoms. It is potentially a chronic illness with considerable morbidity, and a high rate of relapse and recurrence. Major depression has a bidirectional relationship with chronic diseases, and a strong association with increased age and coexisting mental illnesses (e.g. anxiety disorders). Screening can be performed using clinical tools for major depression, such as the Patient Health Questionaire-2, Patient Health Questionaire-9 and Beck Depression Inventory, so that timely treatment can be initiated. An accurate diagnosis of major depression and its severity is essential for prompt treatment to reduce morbidity and mortality. This is the first of a series of articles that illustrates the approach to the management of major depression in primary care. Our next articles will cover suicide risk assessment in a depressed patient and outline the basic principles of management and treatment modalities. PMID:27872937

Semantic Approaches for Knowledge Discovery and Retrieval in Biomedicine

DEFF Research Database (Denmark)

Wilkowski, Bartlomiej

This thesis discusses potential applications of semantics to the recent literaturebased informatics systems to facilitate knowledge discovery, hypothesis generation, and literature retrieval in the domain of biomedicine. The approaches presented herein make use of semantic information extracted...

The neural basis of social risky decision making in females with major depressive disorder.

Science.gov (United States)

Shao, Robin; Zhang, Hui-jun; Lee, Tatia M C

2015-01-01

Recent evidence indicates that Major Depressive Disorder (MDD) may be associated with reduced tendency of committing noncompliant actions during social decision-making even when the risk of being punished is low. The neural underpinnings of this behavioral pattern are unknown, although it likely relates to compromised functioning of the lateral prefrontal-striatal/limbic networks implicated in executive control, emotion regulation and risk/value-based instrumental behaviors. We employed a modified trust game (TG) that provided explicit information on the risk levels of cheating behaviors being detected and punished. Behavioral and neuro-image data were acquired and analyzed from 14 first-episode female MDD patients and 15 age- and gender-matched controls performing the role of trustee in the TG. Relative to controls, MDD patients exhibited less behavioral switching to making cheating choices under low risk, and reduced activity in the dorsal putamen, anterior insula and dorsolateral prefrontal cortex (DLPFC) during making low-risk cheating versus benevolent choices, with limited evidence indicating abnormal bilateral inferior frontal gyrus activities of patients when making high-risk cheating versus benevolent choices. Patients' left dorsal putamen/anterior insular signals correlated positively with their frequency of low-risk cheating. MDD patients' symptom severity correlated positively with their signals in the lateral prefrontal networks during decision-making. A psycho-physiological interaction analysis provided tentative evidence for the recruitment of IFG-striatal/limbic circuitry among the control participants, but greater frontopolar-striatal/limbic connectivity among the MDD patients, during low-risk decision-making. We propose that making risky social decisions based on the balancing of self-gain and other's welfare relies on the functioning of the integrated lateral prefrontal-striatal/limbic networks, which are less efficient and dysregulated among MDD

The discovery and development of antiretroviral agents

NARCIS (Netherlands)

Lange, Joep M. A.; Ananworanich, Jintanat

2014-01-01

Since the discovery of HIV as the causative agent of AIDS in 1983/1984, remarkable progress has been made in finding antiretroviral drugs (ARVs) that are effective against it. A major breakthrough occurred in 1996 when it was found that triple drug therapy (HAART) could durably suppress viral

Bioenergy Knowledge Discovery Framework Fact Sheet

Energy Technology Data Exchange (ETDEWEB)

None

2017-07-01

The Bioenergy Knowledge Discovery Framework (KDF) supports the development of a sustainable bioenergy industry by providing access to a variety of data sets, publications, and collaboration and mapping tools that support bioenergy research, analysis, and decision making. In the KDF, users can search for information, contribute data, and use the tools and map interface to synthesize, analyze, and visualize information in a spatially integrated manner.

X-Raying Neighbour Discovery in a Wireless Sensor Network

African Journals Online (AJOL)

Shuaibu et al.

special neighbour discovery scheme is needed instead. This is the fulcrum .... Similarly, network nodes do not usually switch to a special sleep state in Mobile ... in (P. Dutta and. D. Culler, 2008) make a case for scheduling the wake-up times.

Phenotypic and genomic comparison of Mycobacterium aurum and surrogate model species to Mycobacterium tuberculosis: implications for drug discovery.

Science.gov (United States)

Namouchi, Amine; Cimino, Mena; Favre-Rochex, Sandrine; Charles, Patricia; Gicquel, Brigitte

2017-07-13

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and represents one of the major challenges facing drug discovery initiatives worldwide. The considerable rise in bacterial drug resistance in recent years has led to the need of new drugs and drug regimens. Model systems are regularly used to speed-up the drug discovery process and circumvent biosafety issues associated with manipulating M. tuberculosis. These include the use of strains such as Mycobacterium smegmatis and Mycobacterium marinum that can be handled in biosafety level 2 facilities, making high-throughput screening feasible. However, each of these model species have their own limitations. We report and describe the first complete genome sequence of Mycobacterium aurum ATCC23366, an environmental mycobacterium that can also grow in the gut of humans and animals as part of the microbiota. This species shows a comparable resistance profile to that of M. tuberculosis for several anti-TB drugs. The aims of this study were to (i) determine the drug resistance profile of a recently proposed model species, Mycobacterium aurum, strain ATCC23366, for anti-TB drug discovery as well as Mycobacterium smegmatis and Mycobacterium marinum (ii) sequence and annotate the complete genome sequence of this species obtained using Pacific Bioscience technology (iii) perform comparative genomics analyses of the various surrogate strains with M. tuberculosis (iv) discuss how the choice of the surrogate model used for drug screening can affect the drug discovery process. We describe the complete genome sequence of M. aurum, a surrogate model for anti-tuberculosis drug discovery. Most of the genes already reported to be associated with drug resistance are shared between all the surrogate strains and M. tuberculosis. We consider that M. aurum might be used in high-throughput screening for tuberculosis drug discovery. We also highly recommend the use of different model species during the drug discovery screening process.

Pharmacological screening technologies for venom peptide discovery.

Science.gov (United States)

Prashanth, Jutty Rajan; Hasaballah, Nojod; Vetter, Irina

2017-12-01

Venomous animals occupy one of the most successful evolutionary niches and occur on nearly every continent. They deliver venoms via biting and stinging apparatuses with the aim to rapidly incapacitate prey and deter predators. This has led to the evolution of venom components that act at a number of biological targets - including ion channels, G-protein coupled receptors, transporters and enzymes - with exquisite selectivity and potency, making venom-derived components attractive pharmacological tool compounds and drug leads. In recent years, plate-based pharmacological screening approaches have been introduced to accelerate venom-derived drug discovery. A range of assays are amenable to this purpose, including high-throughput electrophysiology, fluorescence-based functional and binding assays. However, despite these technological advances, the traditional activity-guided fractionation approach is time-consuming and resource-intensive. The combination of screening techniques suitable for miniaturization with sequence-based discovery approaches - supported by advanced proteomics, mass spectrometry, chromatography as well as synthesis and expression techniques - promises to further improve venom peptide discovery. Here, we discuss practical aspects of establishing a pipeline for venom peptide drug discovery with a particular emphasis on pharmacology and pharmacological screening approaches. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

Mass spectrometry-driven drug discovery for development of herbal medicine.

Science.gov (United States)

Zhang, Aihua; Sun, Hui; Wang, Xijun

2018-05-01

Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes. © 2016 Wiley Periodicals, Inc.

Inseparability of science history and discovery

Directory of Open Access Journals (Sweden)

J. M. Herndon

2010-04-01

Full Text Available Science is very much a logical progression through time. Progressing along a logical path of discovery is rather like following a path through the wilderness. Occasionally the path splits, presenting a choice; the correct logical interpretation leads to further progress, the wrong choice leads to confusion. By considering deeply the relevant science history, one might begin to recognize past faltering in the logical progression of observations and ideas and, perhaps then, to discover new, more precise understanding. The following specific examples of science faltering are described from a historical perspective: (1 Composition of the Earth's inner core; (2 Giant planet internal energy production; (3 Physical impossibility of Earth-core convection and Earth-mantle convection, and; (4 Thermonuclear ignition of stars. For each example, a revised logical progression is described, leading, respectively, to: (1 Understanding the endo-Earth's composition; (2 The concept of nuclear georeactor origin of geo- and planetary magnetic fields; (3 The invalidation and replacement of plate tectonics; and, (4 Understanding the basis for the observed distribution of luminous stars in galaxies. These revised logical progressions clearly show the inseparability of science history and discovery. A different and more fundamental approach to making scientific discoveries than the frequently discussed variants of the scientific method is this: An individual ponders and through tedious efforts arranges seemingly unrelated observations into a logical sequence in the mind so that causal relationships become evident and new understanding emerges, showing the path for new observations, for new experiments, for new theoretical considerations, and for new discoveries. Science history is rich in "seemingly unrelated observations" just waiting to be logically and causally related to reveal new discoveries.

Discovery – Ch14.18 Immunotherapy to Treat Neuroblastoma

Science.gov (United States)

Neuroblastoma is rare yet it's the most common cancer affecting infants. Prior to a discovery 20 years in the making, there was little hope for survival in children with advanced stages of the disease. Today, research is leading to a brighter outlook.

Discovery – Methotrexate: Chemotherapy Treatment for Cancer

Science.gov (United States)

Prior to the 1950s, treatment for the majority of cancers was limited to either surgery or the use of radiation. The discovery of the use of methotrexate in curing a rare cancer marked the first time a cancer had been cured. This led to the development of many of today’s common cancer treatments.

WHAT MAKES THINGS GO.

Science.gov (United States)

Mobilization for Youth, Inc., New York, NY.

THE INITIAL QUESTION IN THE TITLE IS ANSWERED THROUGH SIMPLE EXPERIMENTS FOR CULTURALLY DISADVANTAGED CHILDREN IN ELEMENTARY SCHOOL. MUSCLES, RUNNING, WATER, WIND, STEAM, FAST BURNING AND ELECTRICITY ARE FOUND TO "MAKE THINGS GO." USING THESE BASIC DISCOVERIES, VOCABULARY IS BUILT UP BY WORKING WITH DIFFERENT WORDS RELATING TO THE…

Recent advances in inkjet dispensing technologies: applications in drug discovery.

Science.gov (United States)

Zhu, Xiangcheng; Zheng, Qiang; Yang, Hu; Cai, Jin; Huang, Lei; Duan, Yanwen; Xu, Zhinan; Cen, Peilin

2012-09-01

Inkjet dispensing technology is a promising fabrication methodology widely applied in drug discovery. The automated programmable characteristics and high-throughput efficiency makes this approach potentially very useful in miniaturizing the design patterns for assays and drug screening. Various custom-made inkjet dispensing systems as well as specialized bio-ink and substrates have been developed and applied to fulfill the increasing demands of basic drug discovery studies. The incorporation of other modern technologies has further exploited the potential of inkjet dispensing technology in drug discovery and development. This paper reviews and discusses the recent developments and practical applications of inkjet dispensing technology in several areas of drug discovery and development including fundamental assays of cells and proteins, microarrays, biosensors, tissue engineering, basic biological and pharmaceutical studies. Progression in a number of areas of research including biomaterials, inkjet mechanical systems and modern analytical techniques as well as the exploration and accumulation of profound biological knowledge has enabled different inkjet dispensing technologies to be developed and adapted for high-throughput pattern fabrication and miniaturization. This in turn presents a great opportunity to propel inkjet dispensing technology into drug discovery.

DISCOVERY OF A TRANSITING PLANET NEAR THE SNOW-LINE

DEFF Research Database (Denmark)

Kipping, D. M.; Torres, G.; Buchhave, L. A.

2014-01-01

In most theories of planet formation, the snow-line represents a boundary between the emergence of the interior rocky planets and the exterior ice giants. The wide separation of the snow-line makes the discovery of transiting worlds challenging, yet transits would allow for detailed subsequent...

Zebrafish models in neuropsychopharmacology and CNS drug discovery.

Science.gov (United States)

Khan, Kanza M; Collier, Adam D; Meshalkina, Darya A; Kysil, Elana V; Khatsko, Sergey L; Kolesnikova, Tatyana; Morzherin, Yury Yu; Warnick, Jason E; Kalueff, Allan V; Echevarria, David J

2017-07-01

Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets. © 2017 The British Pharmacological Society.

Discoveries by the Fermi Gamma Ray Space Telescope

Science.gov (United States)

Gehrels, Neil

2011-01-01

Fermi is a large space gamma-ray mission developed by NASA and the DOE with major contributions from France, Germany, Italy, Japan and Sweden. It was launched in June 2008 and has been performing flawlessly since then. The main instrument is the Large Area Telescope (LAT) operating in the 20 MeV to 300 GeV range and a smaller monitor instrument is the Gamma-ray Burst Monitor (GBM) operating in the 8 keV to 40 MeV range. New findings are occurring every week. Some of the key discoveries are: 1) Discovery of many new gamma-ray pulsars, including gamma-ray only and millisecond pulsars. 2) Detection of high energy gamma-ray emission from globular clusters, most likely due to summed emission from msec pulsars. 3) Discovery of delayed and extended high energy gamma-ray emission from short and long gamma-ray busts. 4) Detection of approximately 250 gamma-ray bursts per year with the GBM instrument. 5) Most accurate measurement of the cosmic ray electron spectrum between 30 GeV and 1 TeV, showing some excess above the conventional diffusion model. The talk will present the new discoveries and their implications.

State of the Universe 2007 new images, discoveries, and events

CERN Document Server

Ratcliffe, Martin A

2007-01-01

This book is the first regular annual to review each year's major astronomical discoveries. Its aim (and subsequent volumes issued annually) is to provide an annual astronomy review suitable for the popular science level reader.

Topology Discovery Using Cisco Discovery Protocol

OpenAIRE

Rodriguez, Sergio R.

2009-01-01

In this paper we address the problem of discovering network topology in proprietary networks. Namely, we investigate topology discovery in Cisco-based networks. Cisco devices run Cisco Discovery Protocol (CDP) which holds information about these devices. We first compare properties of topologies that can be obtained from networks deploying CDP versus Spanning Tree Protocol (STP) and Management Information Base (MIB) Forwarding Database (FDB). Then we describe a method of discovering topology ...

“The Milan Papyrus” – Seminal Discovery of New Hellenistic Verses

Directory of Open Access Journals (Sweden)

Jelena Isak Kres

2006-07-01

Full Text Available The publication of some newly discovered poems, probably to be attributed to the Hellenistic epigrammatist Posidippus of Pella, is the most significant recent contribution to the corpus of Greek literature. The sheer amount of the poetry and the light which it sheds on our understanding of the literary period makes it the most important discovery in decades, comparable to the papyrus discoveries of Bacchylides, Menander, and Sappho. Moreover, the text is considered to be the earliest collection of Greek poetry organised on aesthetic principles.

Cross-Layer Service Discovery Mechanism for OLSRv2 Mobile Ad Hoc Networks

Directory of Open Access Journals (Sweden)

M. Isabel Vara

2015-07-01

Full Text Available Service discovery plays an important role in mobile ad hoc networks (MANETs. The lack of central infrastructure, limited resources and high mobility make service discovery a challenging issue for this kind of network. This article proposes a new service discovery mechanism for discovering and advertising services integrated into the Optimized Link State Routing Protocol Version 2 (OLSRv2. In previous studies, we demonstrated the validity of a similar service discovery mechanism integrated into the previous version of OLSR (OLSRv1. In order to advertise services, we have added a new type-length-value structure (TLV to the OLSRv2 protocol, called service discovery message (SDM, according to the Generalized MANET Packet/Message Format defined in Request For Comments (RFC 5444. Each node in the ad hoc network only advertises its own services. The advertisement frequency is a user-configurable parameter, so that it can be modified depending on the user requirements. Each node maintains two service tables, one to store information about its own services and another one to store information about the services it discovers in the network. We present simulation results, that compare our service discovery integrated into OLSRv2 with the one defined for OLSRv1 and with the integration of service discovery in Ad hoc On-demand Distance Vector (AODV protocol, in terms of service discovery ratio, service latency and network overhead.

Cross-Layer Service Discovery Mechanism for OLSRv2 Mobile Ad Hoc Networks.

Science.gov (United States)

Vara, M Isabel; Campo, Celeste

2015-07-20

Service discovery plays an important role in mobile ad hoc networks (MANETs). The lack of central infrastructure, limited resources and high mobility make service discovery a challenging issue for this kind of network. This article proposes a new service discovery mechanism for discovering and advertising services integrated into the Optimized Link State Routing Protocol Version 2 (OLSRv2). In previous studies, we demonstrated the validity of a similar service discovery mechanism integrated into the previous version of OLSR (OLSRv1). In order to advertise services, we have added a new type-length-value structure (TLV) to the OLSRv2 protocol, called service discovery message (SDM), according to the Generalized MANET Packet/Message Format defined in Request For Comments (RFC) 5444. Each node in the ad hoc network only advertises its own services. The advertisement frequency is a user-configurable parameter, so that it can be modified depending on the user requirements. Each node maintains two service tables, one to store information about its own services and another one to store information about the services it discovers in the network. We present simulation results, that compare our service discovery integrated into OLSRv2 with the one defined for OLSRv1 and with the integration of service discovery in Ad hoc On-demand Distance Vector (AODV) protocol, in terms of service discovery ratio, service latency and network overhead.

Application of PBPK modelling in drug discovery and development at Pfizer.

Science.gov (United States)

Jones, Hannah M; Dickins, Maurice; Youdim, Kuresh; Gosset, James R; Attkins, Neil J; Hay, Tanya L; Gurrell, Ian K; Logan, Y Raj; Bungay, Peter J; Jones, Barry C; Gardner, Iain B

2012-01-01

Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. Using examples from the literature and our own company, we have shown how PBPK techniques can be utilized through the stages of drug discovery and development to increase efficiency, reduce the need for animal studies, replace clinical trials and to increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however, some limitations need to be addressed to realize its application and utility more broadly.

The limits of de novo DNA motif discovery.

Directory of Open Access Journals (Sweden)

David Simcha

Full Text Available A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify "motifs" that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery-searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA "background" sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are "too null," resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where "ground truth" is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced "over-fitting" in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of

Arational heuristic model of economic decision making

OpenAIRE

Grandori, Anna

2010-01-01

The article discuss the limits of both the rational actor and the behavioral paradigms in explaining and guiding innovative decision making and outlines a model of economic decision making that in the course of being 'heuristic' (research and discovery oriented) is also 'rational' (in the broad sense of following correct reasoning and scientific methods, non 'biasing'). The model specifies a set of 'rational heuristics' for innovative decision making, for the various sub-processes of problem ...

Motivating Communities To Go Beyond the Discovery Plateau

Science.gov (United States)

Habermann, T.; Kozimor, J.

2014-12-01

Years of emphasizing discovery and minimal metadata requirements have resulted in a culture that accepts that metadata are for discovery and complete metadata are too complex or difficult for researchers to understand and create. Evolving the culture past this "data-discovery plateau" requires a multi-faceted approach that addresses the rational and emotional sides of the problem. On the rational side, scientists know that data and results must be well documented in order to be reproducible, re-usable, and trustworthy. We need tools that script critical moves towards well-described destinations and help identify members of the community that are already leading the way towards those destinations. We need mechanisms that help those leaders share their experiences and examples. On the emotional side, we need to emphasize that high-quality metadata makes data trustworthy, divide the improvement process into digestible pieces and create mechanisms for clearly identifying and rewarding progress. We also need to provide clear opportunities for community members to increase their expertise and to share their skills.

[Affective and cognitive decision making in major depression: influence of the prefrontal cortex, serotonin transporter genotype and personality traits].

Science.gov (United States)

Must, Anita; Horváth, Szatmár; Janka, Zoltán

2008-05-30

Patients with major depressive disorder (MDD) show neuropsychological impairments, including deficient executive functions and suboptimal decision-making strategies, which are mediated by several brain regions. In the development of these symptoms the pathology of the prefrontal cortex (PFC), including the dorsolateral, ventromedial and orbitofrontal regions, may also play an important role. Neuropsychological assessment is a useful tool in detecting and measuring these deficiencies, showing that patients with MDD exhibit altered sensitivity to reward and punishment. However, impairment of emotional decision-making strategies in MDD is influenced by genetic variations (5-HTTLPR polymorphism) and personality traits, which seem to have a higher predictive value on decision making performance than the clinical symptoms.

14 CFR 406.143 - Discovery.

Science.gov (United States)

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...

Centenary of the discovery of superconductivity

CERN Multimedia

Anaïs Vernède

2011-01-01

To mark the centenary of the discovery of the phenomenon of superconductivity, MANEP and the University of Geneva are organising open days at the PhysiScope between 8 and 15 April 2011. On 13 April CERN will make a contribution to the series of events with a lecture on superconductivity followed by a demonstration of the phenomenon at the Globe   Historic graph showing the superconducting transition of mercury, measured in Leiden in 1911 by H. Kamerlingh Onnes. On 8 April 2011 it will be a hundred years since the discovery of superconductivity by the Dutch physicist Kamerlingh Onnes. To mark the occasion, the University of Geneva and MANEP are organising a week-long interactive workshop at the PhysiScope. “The purpose of this initiative is to introduce the general public to this spectacular phenomenon by giving them an opportunity to take part in entertaining experiments”, explains Adriana Aleman, Head of Communications of the University of Geneva. As its contribution to the e...

Discovery: Under the Microscope at Kennedy Space Center

Science.gov (United States)

Howard, Philip M.

2013-01-01

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

Higgs Discovery

DEFF Research Database (Denmark)

Sannino, Francesco

2013-01-01

has been challenged by the discovery of a not-so-heavy Higgs-like state. I will therefore review the recent discovery \\cite{Foadi:2012bb} that the standard model top-induced radiative corrections naturally reduce the intrinsic non-perturbative mass of the composite Higgs state towards the desired...... via first principle lattice simulations with encouraging results. The new findings show that the recent naive claims made about new strong dynamics at the electroweak scale being disfavoured by the discovery of a not-so-heavy composite Higgs are unwarranted. I will then introduce the more speculative......I discuss the impact of the discovery of a Higgs-like state on composite dynamics starting by critically examining the reasons in favour of either an elementary or composite nature of this state. Accepting the standard model interpretation I re-address the standard model vacuum stability within...

Using the iPlant collaborative discovery environment.

Science.gov (United States)

Oliver, Shannon L; Lenards, Andrew J; Barthelson, Roger A; Merchant, Nirav; McKay, Sheldon J

2013-06-01

The iPlant Collaborative is an academic consortium whose mission is to develop an informatics and social infrastructure to address the "grand challenges" in plant biology. Its cyberinfrastructure supports the computational needs of the research community and facilitates solving major challenges in plant science. The Discovery Environment provides a powerful and rich graphical interface to the iPlant Collaborative cyberinfrastructure by creating an accessible virtual workbench that enables all levels of expertise, ranging from students to traditional biology researchers and computational experts, to explore, analyze, and share their data. By providing access to iPlant's robust data-management system and high-performance computing resources, the Discovery Environment also creates a unified space in which researchers can access scalable tools. Researchers can use available Applications (Apps) to execute analyses on their data, as well as customize or integrate their own tools to better meet the specific needs of their research. These Apps can also be used in workflows that automate more complicated analyses. This module describes how to use the main features of the Discovery Environment, using bioinformatics workflows for high-throughput sequence data as examples. © 2013 by John Wiley & Sons, Inc.

A historical reflection on the discovery of human retroviruses.

Science.gov (United States)

Vahlne, Anders

2009-05-01

The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined. The first human retroviruses (HTLV-I) was first reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma and coworkers in 1981. These discoveries were in turn dependent on the previous discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor as it was called then. HTLV-II was described by Gallo's group in 1982. A human retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the morphology of a lentivirus was in my mind described for the first time by Luc Montagnier in an oral presentation at Cold Spring Harbor in September of 1983. This virus was isolated from a patient with lymphadenopathy using the protocol previously described for HTLV by Gallo. The first peer reviewed paper by Montagnier's group of such a retrovirus, isolated from two siblings of whom one with AIDS, appeared in Lancet in April of 1984. However, the proof that a new human retrovirus (HIV-1) was the cause of AIDS was first established in four publications by Gallo's group in the May 4th issue of Science in 1984.

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

Science.gov (United States)

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.

The scientist as philosopher philosophical consequences of great scientific discoveries

CERN Document Server

Weinert, Friedel

2005-01-01

How do major scientific discoveries reshape their originators’, and our own, sense of reality and concept of the physical world? The Scientist as Philosopher explores the interaction between physics and philosophy. Clearly written and well illustrated, the book first places the scientist-philosophers in the limelight as we learn how their great scientific discoveries forced them to reconsider the time-honored notions with which science had described the natural world. Then, the book explains that what we understand by nature and science have undergone fundamental conceptual changes as a result of the discoveries of electromagnetism, thermodynamics and atomic structure. Even more dramatically, the quantum theory and special theory of relativity questioned traditional assumptions about causation and the passage of time. The author concludes that the dance between science and philosophy is an evolutionary process, which will keep them forever entwined.

Beyond Discovery

DEFF Research Database (Denmark)

Korsgaard, Steffen; Sassmannshausen, Sean Patrick

2017-01-01

In this chapter we explore four alternatives to the dominant discovery view of entrepreneurship; the development view, the construction view, the evolutionary view, and the Neo-Austrian view. We outline the main critique points of the discovery presented in these four alternatives, as well...

Knowledge-Based Topic Model for Unsupervised Object Discovery and Localization.

Science.gov (United States)

Niu, Zhenxing; Hua, Gang; Wang, Le; Gao, Xinbo

Unsupervised object discovery and localization is to discover some dominant object classes and localize all of object instances from a given image collection without any supervision. Previous work has attempted to tackle this problem with vanilla topic models, such as latent Dirichlet allocation (LDA). However, in those methods no prior knowledge for the given image collection is exploited to facilitate object discovery. On the other hand, the topic models used in those methods suffer from the topic coherence issue-some inferred topics do not have clear meaning, which limits the final performance of object discovery. In this paper, prior knowledge in terms of the so-called must-links are exploited from Web images on the Internet. Furthermore, a novel knowledge-based topic model, called LDA with mixture of Dirichlet trees, is proposed to incorporate the must-links into topic modeling for object discovery. In particular, to better deal with the polysemy phenomenon of visual words, the must-link is re-defined as that one must-link only constrains one or some topic(s) instead of all topics, which leads to significantly improved topic coherence. Moreover, the must-links are built and grouped with respect to specific object classes, thus the must-links in our approach are semantic-specific , which allows to more efficiently exploit discriminative prior knowledge from Web images. Extensive experiments validated the efficiency of our proposed approach on several data sets. It is shown that our method significantly improves topic coherence and outperforms the unsupervised methods for object discovery and localization. In addition, compared with discriminative methods, the naturally existing object classes in the given image collection can be subtly discovered, which makes our approach well suited for realistic applications of unsupervised object discovery.Unsupervised object discovery and localization is to discover some dominant object classes and localize all of object

Integration of Proteomics, Bioinformatics, and Systems Biology in Traumatic Brain Injury Biomarker Discovery

Science.gov (United States)

Guingab-Cagmat, J.D.; Cagmat, E.B.; Hayes, R.L.; Anagli, J.

2013-01-01

Traumatic brain injury (TBI) is a major medical crisis without any FDA-approved pharmacological therapies that have been demonstrated to improve functional outcomes. It has been argued that discovery of disease-relevant biomarkers might help to guide successful clinical trials for TBI. Major advances in mass spectrometry (MS) have revolutionized the field of proteomic biomarker discovery and facilitated the identification of several candidate markers that are being further evaluated for their efficacy as TBI biomarkers. However, several hurdles have to be overcome even during the discovery phase which is only the first step in the long process of biomarker development. The high-throughput nature of MS-based proteomic experiments generates a massive amount of mass spectral data presenting great challenges in downstream interpretation. Currently, different bioinformatics platforms are available for functional analysis and data mining of MS-generated proteomic data. These tools provide a way to convert data sets to biologically interpretable results and functional outcomes. A strategy that has promise in advancing biomarker development involves the triad of proteomics, bioinformatics, and systems biology. In this review, a brief overview of how bioinformatics and systems biology tools analyze, transform, and interpret complex MS datasets into biologically relevant results is discussed. In addition, challenges and limitations of proteomics, bioinformatics, and systems biology in TBI biomarker discovery are presented. A brief survey of researches that utilized these three overlapping disciplines in TBI biomarker discovery is also presented. Finally, examples of TBI biomarkers and their applications are discussed. PMID:23750150

Stem cell technology for drug discovery and development.

Science.gov (United States)

Hook, Lilian A

2012-04-01

Stem cells have enormous potential to revolutionise the drug discovery process at all stages, from target identification through to toxicology studies. Their ability to generate physiologically relevant cells in limitless supply makes them an attractive alternative to currently used recombinant cell lines or primary cells. However, realisation of the full potential of stem cells is currently hampered by the difficulty in routinely directing stem cell differentiation to reproducibly and cost effectively generate pure populations of specific cell types. In this article we discuss how stem cells have already been used in the drug discovery process and how novel technologies, particularly in relation to stem cell differentiation, can be applied to attain widespread adoption of stem cell technology by the pharmaceutical industry. Copyright © 2011 Elsevier Ltd. All rights reserved.

"Eureka, Eureka!" Discoveries in Science

Science.gov (United States)

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…

30 CFR 44.24 - Discovery.

Science.gov (United States)

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...

19 CFR 356.20 - Discovery.

Science.gov (United States)

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...

Chemical Discovery

Science.gov (United States)

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)

Engineering Application Way of Faults Knowledge Discovery Based on Rough Set Theory

International Nuclear Information System (INIS)

Zhao Rongzhen; Deng Linfeng; Li Chao

2011-01-01

For the knowledge acquisition puzzle of intelligence decision-making technology in mechanical industry, to use the Rough Set Theory (RST) as a kind of tool to solve the puzzle was researched. And the way to realize the knowledge discovery in engineering application is explored. A case extracting out the knowledge rules from a concise data table shows out some important information. It is that the knowledge discovery similar to the mechanical faults diagnosis is an item of complicated system engineering project. In where, first of all-important tasks is to preserve the faults knowledge into a table with data mode. And the data must be derived from the plant site and should also be as concise as possible. On the basis of the faults knowledge data obtained so, the methods and algorithms to process the data and extract the knowledge rules from them by means of RST can be processed only. The conclusion is that the faults knowledge discovery by the way is a process of rising upward. But to develop the advanced faults diagnosis technology by the way is a large-scale knowledge engineering project for long time. Every step in which should be designed seriously according to the tool's demands firstly. This is the basic guarantees to make the knowledge rules obtained have the values of engineering application and the studies have scientific significance. So, a general framework is designed for engineering application to go along the route developing the faults knowledge discovery technology.

24 CFR 180.500 - Discovery.

Science.gov (United States)

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...

22 CFR 224.21 - Discovery.

Science.gov (United States)

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...

Panorama 2014 - New oil and gas discoveries

International Nuclear Information System (INIS)

Vially, Roland; Hureau, Geoffroy

2013-12-01

Spending on exploration increased significantly in 2012, and this growth should continue into 2013. Over a period of ten years, exploration budgets have increased five-fold, leading to major discoveries in regions as yet unexplored. In 2012, 25 billion barrels of oil equivalent (Gboe) were revealed. This is more than the average for the whole decade, but less than the amount for the previous year. Although knowledge of the volumes that have been discovered is still very fragmented, they should continue to fall into 2013. The main reason lies in the fact that spending on exploration is being shifted towards assessing discoveries made in previous years in the particularly prolific basins of Brazil and East Africa, while the exploration of border regions - such as the West African pre-salt formation - is still only in its early stages. (authors)

19 CFR 207.109 - Discovery.

Science.gov (United States)

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...

15 CFR 25.21 - Discovery.

Science.gov (United States)

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...

Discovery and development of new antibacterial drugs: learning from experience?

Science.gov (United States)

Jackson, Nicole; Czaplewski, Lloyd; Piddock, Laura J V

2018-06-01

Antibiotic (antibacterial) resistance is a serious global problem and the need for new treatments is urgent. The current antibiotic discovery model is not delivering new agents at a rate that is sufficient to combat present levels of antibiotic resistance. This has led to fears of the arrival of a 'post-antibiotic era'. Scientific difficulties, an unfavourable regulatory climate, multiple company mergers and the low financial returns associated with antibiotic drug development have led to the withdrawal of many pharmaceutical companies from the field. The regulatory climate has now begun to improve, but major scientific hurdles still impede the discovery and development of novel antibacterial agents. To facilitate discovery activities there must be increased understanding of the scientific problems experienced by pharmaceutical companies. This must be coupled with addressing the current antibiotic resistance crisis so that compounds and ultimately drugs are delivered to treat the most urgent clinical challenges. By understanding the causes of the failures and successes of the pharmaceutical industry's research history, duplication of discovery programmes will be reduced, increasing the productivity of the antibiotic drug discovery pipeline by academia and small companies. The most important scientific issues to address are getting molecules into the Gram-negative bacterial cell and avoiding their efflux. Hence screening programmes should focus their efforts on whole bacterial cells rather than cell-free systems. Despite falling out of favour with pharmaceutical companies, natural product research still holds promise for providing new molecules as a basis for discovery.

Competitive intelligence and patent analysis in drug discovery.

Science.gov (United States)

Grandjean, Nicolas; Charpiot, Brigitte; Pena, Carlos Andres; Peitsch, Manuel C

2005-01-01

Patents are a major source of information in drug discovery and, when properly processed and analyzed, can yield a wealth of information on competitors activities, R&D trends, emerging fields, collaborations, among others. This review discusses the current state-of-the-art in textual data analysis and exploration methods as applied to patent analysis.: © 2005 Elsevier Ltd . All rights reserved.

39 CFR 963.14 - Discovery.

Science.gov (United States)

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...

Drug discovery for alopecia: gone today, hair tomorrow.

Science.gov (United States)

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

2015-03-01

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

Genetics of rheumatoid arthritis conributes to biology and drug discovery

NARCIS (Netherlands)

Okada, Yukinori; Wu, Di; Trynka, Gosia; Raj, Towfique; Terao, Chikashi; Ikari, Katsunori; Kochi, Yuta; Ohmura, Koichiro; Suzuki, A.; Yoshida, S.; Graham, R.R.; Manoharan, A.; Ortmann, W.; Bhangale, T.; Denny, J.C.; Carroll, R.J.; Eyler, A.E.; Greenberg, J.D.; Kremer, J.M.; Pappas, D.A.; Jiang, L.; Yin, L.; Ye, L.; Su, D.F.; Yang, J.; Xie, G.; Keystone, E.; Westra, H.J.; Esko, T.; Metspalu, A.; Zhou, X.; Gupta, N.; Mirel, D.; Stahl, Eli A.; Diogo, D.; Cui, J.; Liao, K.; Guo, M.H.; Myouzen, K.; Kawaguchi, T.; Coenen, M.J.; van Riel, P.L.; van de Laar, Mart A.F.J.; Guchelaar, H.J.; Huizinga, T.W.; Dieudé, P.; Mariette, X.; Louis Bridges Jr, S.; Zhernakova, A.; Toes, R.E.; Tak, P.P.; Miceli-Richard, C.; Bang, S.Y.; Lee, H.S.; Martin, J.; Gonzales-Gay, M.A.; Rodriguez-Rodriguez, L.; Rantapää-Dhlqvist, S.; Arlestig, L.; Choi, H.K.; Kamatani, Y.; Galan, P.; Lathrop, M.; Eyre, S.; Bowes, J.; Barton, A.; de Vries, N.; Moreland, L.W.; Criswell, L.A.; Karlson, E.W.; Taniguchi, A.; Yamada, R; Kubo, M.; Bae, S.C.; Worthington, J.; Padyukov, L.; Klareskog, L.; Gregersen, Peter K.; Raychaudhuri, S.; Stranger, B.E.; de Jager, P.L.; Franke, L.; Visscher, P.M.; Brown, M.A.; Yamanaka, H.; Mimori, T.; Takahashi, A.; Xu, H.; Behrens, T.W.; Siminovitch, K.A.; Momohara, S.; Matsuda, F.; Yamamoto, K.; Plenge, Robert M.

2013-01-01

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed

The SUrvey for Pulsars and Extragalactic Radio Bursts – II. New FRB discoveries and their follow-up

NARCIS (Netherlands)

Bhandari, S.; Keane, E.F.; Barr, E.D.; Jameson, A.; Petroff, E.; Johnston, S.; Bailes, M.; Bhat, N.D.R.; Burgay, M.; Burke-Spolaor, S.; Caleb, M.; Eatough, R.P.; Flynn, C.; Green, J.A.; Jankowski, F.; Kramer, M.; Krishnan, V Venkatraman; Morello, V.; Possenti, A.; Stappers, B.; Tiburzi, C.; van Straten, W.; Andreoni, I.; Butterley, T.; Chandra, P.; Cooke, J.; Corongiu, A.; Coward, D.M.; Dhillon, V.S.; Dodson, R.; Hardy, L.K.; Howell, E.J.; Jaroenjittichai, P.; Klotz, A.; Littlefair, S.P.; Marsh, T.R.; Mickaliger, M.; Muxlow, T.; Perrodin, D.; Pritchard, D.; Sawangwit, U.; Terai, T.; Tominaga, N.; Torne, P.; Totani, T.; Trois, A.; Turpin, D.; Niino, Y.; Wilson, R.W.; Albert, A.; André, M.; Anghinolfi, M.; Anton, G.; Ardid, M.; Aubert, J.J.; Avgitas, T.; Baret, B.; Barrios-Marti, J.; Basa, S.; Belhorma, B.; Bertin, V.; Biagi, S.; Bormuth, R.; Bourret, S.; Bouwhuis, M.C.; Brânzas, H.; Bruijn, R.; Brunner, J.; Busto, J.; Capone, A.; Caramete, L.; Carr, J.; Celli, S.; Cherkaoui El Moursli, R.; Chiarusi, T.; Circella, M.; Coelho, J.A.B.; Coleiro, A.; Coniglione, R.; Costantini, H.; Coyle, P.; Creusot, A.; Díaz, A.F.; Deschamps, A.; De Bonis, G.; Distefano, C.; Di Palma, I.; Domi, A.; Donzaud, C.; Dornic, D.; Drouhin, D.; Eberl, T.; El Bojaddaini, I.; El Khayati, N.; Elsässer, D.; Enzenhöfer, A.; Ettahiri, A.; Fassi, F.; Felis, I.; Fusco, L.A.; Gay, P.; Giordano, V.; Glotin, H.; Grégoire, T.; Gracia-Ruiz, R.; Graf, K.; Hallmann, S.; van Haren, H.; Heijboer, A.J.; Hello, Y.; Hernandez-Rey, J.J.; Hößl, J.; Hofestädt, J.; Hugon, C.; Illuminati, G.; James, C.W.; de Jong, M.; Jongen, M.; Kadler, M.; Kalekin, O.; Katz, U.; Kießling, D.; Kouchner, A.; Kreter, M.; Kreykenbohm, I.; Kulikovskiy, V.; Lachaud, C.; Lahmann, R.; Lefevre, D.; Leonora, E.; Loucatos, S.; Marcelin, M.; Margiotta, A.; Marinelli, A.; Martinez-Mora, J.A.; Mele, R.; Melis, K.; Michael, T.; Migliozzi, P.; Moussa, A.; Navas, S.; Nezri, E.; Organokov, M.; Pavalas, G.E.; Pellegrino, C.; Perrina, C.; Piattelli, P.; Popa, V.; Pradier, T.; Quinn, L.; Racca, C.; Riccobene, G.; Sanchez-Losa, A.; Saldaña, M.; Salvadori, I.; Samtleben, D.F.E.; Sanguineti, M.; Sapienza, P.; Schussler, F.; Sieger, C.; Spurio, M.; Stolarczyk, Th.; Taiuti, M.; Tayalati, Y.; Trovato, A.; Turpin, D.; Tönnis, C.; Vallage, B.; Van Elewyck, V.; Versari, F.; Vivolo, D.; Vizzocca, A.; Wilms, J.; Zornoza, J.D.; Zúñiga, J.

2017-01-01

We report the discovery of four Fast Radio Bursts (FRBs) in the ongoing SUrvey for Pulsars and Extragalactic Radio Bursts at the Parkes Radio Telescope: FRBs 150610, 151206, 151230 and 160102. Our real-time discoveries have enabled us to conduct extensive, rapid multimessenger follow-up at 12 major

A historical reflection on the discovery of human retroviruses

Directory of Open Access Journals (Sweden)

Vahlne Anders

2009-05-01

Full Text Available Abstract The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined. The first human retroviruses (HTLV-I was first reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma and coworkers in 1981. These discoveries were in turn dependent on the previous discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor as it was called then. HTLV-II was described by Gallo's group in 1982. A human retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the morphology of a lentivirus was in my mind described for the first time by Luc Montagnier in an oral presentation at Cold Spring Harbor in September of 1983. This virus was isolated from a patient with lymphadenopathy using the protocol previously described for HTLV by Gallo. The first peer reviewed paper by Montagnier's group of such a retrovirus, isolated from two siblings of whom one with AIDS, appeared in Lancet in April of 1984. However, the proof that a new human retrovirus (HIV-1 was the cause of AIDS was first established in four publications by Gallo's group in the May 4th issue of Science in 1984.

Exciting Discoveries on the Health Effects of Family Violence: Where We Are, Where We Need to Go

Science.gov (United States)

Kendall-Tackett, Kathleen

2005-01-01

In the 20 years since the founding of the "Journal of Interpersonal Violence," there have been exciting new discoveries on the long-term physical health effects of family violence. As exciting as these discoveries have been, we still know little about why the experience of family violence makes people sick. Some of the most promising areas of…

Evaluating the inverse reasoning account of object discovery.

Science.gov (United States)

Carroll, Christopher D; Kemp, Charles

2015-06-01

People routinely make inferences about unobserved objects. A hotel guest with welts on his arms, for example, will often worry about bed bugs. The discovery of unobserved objects almost always involves a backward inference from some observed effects (e.g., welts) to unobserved causes (e.g., bed bugs). The inverse reasoning account, which is typically formalized as Bayesian inference, posits that the strength of a backward inference is closely connected to the strength of the corresponding forward inference from the unobserved causes to the observed effects. We evaluated the inverse reasoning account of object discovery in three experiments where participants were asked to discover the unobserved "attractors" and "repellers" that controlled a "particle" moving within an arena. Experiments 1 and 2 showed that participants often failed to provide the best explanations for various particle motions, even when the best explanations were simple and when participants enthusiastically endorsed these explanations when presented with them. This failure demonstrates that object discovery is critically dependent on the processes that support hypothesis generation-processes that the inverse reasoning account does not explain. Experiment 3 demonstrated that people sometimes generate explanations that are invalid even according to their own forward inferences, suggesting that the psychological processes that support forward and backward inference are less intertwined than the inverse reasoning account suggests. The experimental findings support an alternative account of object discovery in which people rely on heuristics to generate possible explanations. Copyright © 2015 Elsevier B.V. All rights reserved.

Usability of Discovery Portals

OpenAIRE

Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.

2013-01-01

As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals are not spatial data experts but professionals with limited spatial knowledge, and a focus outside the spatial domain. An exploratory usability experiment was carried out in which three discovery p...

Business Model Discovery by Technology Entrepreneurs

Directory of Open Access Journals (Sweden)

Steven Muegge

2012-04-01

Full Text Available Value creation and value capture are central to technology entrepreneurship. The ways in which a particular firm creates and captures value are the foundation of that firm's business model, which is an explanation of how the business delivers value to a set of customers at attractive profits. Despite the deep conceptual link between business models and technology entrepreneurship, little is known about the processes by which technology entrepreneurs produce successful business models. This article makes three contributions to partially address this knowledge gap. First, it argues that business model discovery by technology entrepreneurs can be, and often should be, disciplined by both intention and structure. Second, it provides a tool for disciplined business model discovery that includes an actionable process and a worksheet for describing a business model in a form that is both concise and explicit. Third, it shares preliminary results and lessons learned from six technology entrepreneurs applying a disciplined process to strengthen or reinvent the business models of their own nascent technology businesses.

The Highly Relativistic Binary Pulsar PSR J0737-3039A: Discovery and Implications

OpenAIRE

Burgay, M.; D'Amico, N.; Possenti, A.; Manchester, R. N.; Lyne, A. G.; Joshi, B. C.; McLaughlin, M. A.; Kramer, M.; Sarkissian, J. M.; Camilo, F.; Kalogera, V.; Kim, C.; Lorimer, D. R.

2004-01-01

PSR J0737-3039A is a millisecond pulsar with a spin period of 22.7 ms included in a double-neutron star system with an orbital period of 2.4 hrs. Its companion has also been detected as a radio pulsar, making this binary the first known double-pulsar system. Its discovery has important implications for relativistic gravity tests, gravitational wave detection and plasma physics. Here we will shortly describe the discovery of the first pulsar in this unique system and present the first results ...

The Proteomics Big Challenge for Biomarkers and New Drug-Targets Discovery

Science.gov (United States)

Savino, Rocco; Paduano, Sergio; Preianò, Mariaimmacolata; Terracciano, Rosa

2012-01-01

In the modern process of drug discovery, clinical, functional and chemical proteomics can converge and integrate synergies. Functional proteomics explores and elucidates the components of pathways and their interactions which, when deregulated, lead to a disease condition. This knowledge allows the design of strategies to target multiple pathways with combinations of pathway-specific drugs, which might increase chances of success and reduce the occurrence of drug resistance. Chemical proteomics, by analyzing the drug interactome, strongly contributes to accelerate the process of new druggable targets discovery. In the research area of clinical proteomics, proteome and peptidome mass spectrometry-profiling of human bodily fluid (plasma, serum, urine and so on), as well as of tissue and of cells, represents a promising tool for novel biomarker and eventually new druggable targets discovery. In the present review we provide a survey of current strategies of functional, chemical and clinical proteomics. Major issues will be presented for proteomic technologies used for the discovery of biomarkers for early disease diagnosis and identification of new drug targets. PMID:23203042

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

Science.gov (United States)

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

1980-01-01

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

Pathways to new drug discovery in neuropsychiatry

Directory of Open Access Journals (Sweden)

Berk Michael

2012-11-01

Full Text Available Abstract There is currently a crisis in drug discovery for neuropsychiatric disorders, with a profound, yet unexpected drought in new drug development across the spectrum. In this commentary, the sources of this dilemma and potential avenues to redress the issue are explored. These include a critical review of diagnostic issues and of selection of participants for clinical trials, and the mechanisms for identifying new drugs and new drug targets. Historically, the vast majority of agents have been discovered serendipitously or have been modifications of existing agents. Serendipitous discoveries, based on astute clinical observation or data mining, remain a valid option, as is illustrated by the suggestion in the paper by Wahlqvist and colleagues that treatment with sulfonylurea and metformin reduces the risk of affective disorder. However, the identification of agents targeting disorder-related biomarkers is currently proving particularly fruitful. There is considerable hope for genetics as a purist, pathophysiologically valid pathway to drug discovery; however, it is unclear whether the science is ready to meet this promise. Fruitful paradigms will require a break from the orthodoxy, and creativity and risk may well be the fingerprints of success. See related article http://www.biomedcentral.com/1741-7015/10/150

Systems Pharmacology in Small Molecular Drug Discovery

Directory of Open Access Journals (Sweden)

Wei Zhou

2016-02-01

Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

The atom smashers they have one last chance to make the discovery of a lifetime

CERN Document Server

Ross, Monica

2008-01-01

Physicists at Fermilab, the world's most powerful particle accelerator laboratory, are closing in on one of the universe's best-kept secrets: why everything has mass. With the Tevatron, a four-mile underground particle accelerator, the scientists smash matter together at nearly the speed of light to find a particle theorized forty years ago by Scottish scientist Peter Higgs. Scour the subatomic world for the Higgs. Will the discovery happen?

19 CFR 354.10 - Discovery.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Discovery. 354.10 Section 354.10 Customs Duties... ANTIDUMPING OR COUNTERVAILING DUTY ADMINISTRATIVE PROTECTIVE ORDER § 354.10 Discovery. (a) Voluntary discovery. All parties are encouraged to engage in voluntary discovery procedures regarding any matter, not...

36 CFR 1150.63 - Discovery.

Science.gov (United States)

2010-07-01

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

37 CFR 11.52 - Discovery.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 11.52 Section 11... Disciplinary Proceedings; Jurisdiction, Sanctions, Investigations, and Proceedings § 11.52 Discovery. Discovery... establishes that discovery is reasonable and relevant, the hearing officer, under such conditions as he or she...

Genomic prediction unifies animal and plant breeding programs to form platforms for biological discovery

DEFF Research Database (Denmark)

Hickey, John M.; Chiurugwi, Tinashe; Mackay, Ian

2017-01-01

The rate of annual yield increases for major staple crops must more than double relative to current levels in order to feed a predicted global population of 9 billion by 2050. Controlled hybridization and selective breeding have been used for centuries to adapt plant and animal species for human...... that unifies breeding approaches, biological discovery, and tools and methods. Here we compare and contrast some animal and plant breeding approaches to make a case for bringing the two together through the application of genomic selection. We propose a strategy for the use of genomic selection as a unifying...... use. However, achieving higher, sustainable rates of improvement in yields in various species will require renewed genetic interventions and dramatic improvement of agricultural practices. Genomic prediction of breeding values has the potential to improve selection, reduce costs and provide a platform...

Big Data in Drug Discovery.

Science.gov (United States)

Brown, Nathan; Cambruzzi, Jean; Cox, Peter J; Davies, Mark; Dunbar, James; Plumbley, Dean; Sellwood, Matthew A; Sim, Aaron; Williams-Jones, Bryn I; Zwierzyna, Magdalena; Sheppard, David W

2018-01-01

Interpretation of Big Data in the drug discovery community should enhance project timelines and reduce clinical attrition through improved early decision making. The issues we encounter start with the sheer volume of data and how we first ingest it before building an infrastructure to house it to make use of the data in an efficient and productive way. There are many problems associated with the data itself including general reproducibility, but often, it is the context surrounding an experiment that is critical to success. Help, in the form of artificial intelligence (AI), is required to understand and translate the context. On the back of natural language processing pipelines, AI is also used to prospectively generate new hypotheses by linking data together. We explain Big Data from the context of biology, chemistry and clinical trials, showcasing some of the impressive public domain sources and initiatives now available for interrogation. © 2018 Elsevier B.V. All rights reserved.

Usability of Discovery Portals

NARCIS (Netherlands)

Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.

2013-01-01

As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals

14 CFR 16.213 - Discovery.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Discovery. 16.213 Section 16.213... PRACTICE FOR FEDERALLY-ASSISTED AIRPORT ENFORCEMENT PROCEEDINGS Hearings § 16.213 Discovery. (a) Discovery... discovery permitted by this section if a party shows that— (1) The information requested is cumulative or...

28 CFR 76.21 - Discovery.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 76.21 Section 76.21 Judicial... POSSESSION OF CERTAIN CONTROLLED SUBSTANCES § 76.21 Discovery. (a) Scope. Discovery under this part covers... as a general guide for discovery practices in proceedings before the Judge. However, unless otherwise...

40 CFR 27.21 - Discovery.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Discovery. 27.21 Section 27.21... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for..., discovery is available only as ordered by the presiding officer. The presiding officer shall regulate the...

37 CFR 41.150 - Discovery.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 41.150 Section 41... COMMERCE PRACTICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES Contested Cases § 41.150 Discovery. (a) Limited discovery. A party is not entitled to discovery except as authorized in this subpart. The...

14 CFR 13.220 - Discovery.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or...

49 CFR 604.38 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Discovery. 604.38 Section 604.38 Transportation... TRANSPORTATION CHARTER SERVICE Hearings. § 604.38 Discovery. (a) Permissible forms of discovery shall be within the discretion of the PO. (b) The PO shall limit the frequency and extent of discovery permitted by...

15 CFR 719.10 - Discovery.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 719.10 Section 719.10... Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter... the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with this...

24 CFR 26.18 - Discovery.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 26.18 Section 26.18... PROCEDURES Hearings Before Hearing Officers Discovery § 26.18 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery procedures, which may commence at any time after an answer has...

42 CFR 426.532 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Discovery. 426.532 Section 426.532 Public Health... § 426.532 Discovery. (a) General rule. If the Board orders discovery, the Board must establish a reasonable timeframe for discovery. (b) Protective order—(1) Request for a protective order. Any party...

49 CFR 1503.633 - Discovery.

Science.gov (United States)

2010-10-01

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

14 CFR 1264.120 - Discovery.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Discovery. 1264.120 Section 1264.120... PENALTIES ACT OF 1986 § 1264.120 Discovery. (a) The following types of discovery are authorized: (1..., discovery is available only as ordered by the presiding officer. The presiding officer shall regulate the...

22 CFR 128.6 - Discovery.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 128.6 Section 128.6 Foreign... Discovery. (a) Discovery by the respondent. The respondent, through the Administrative Law Judge, may... discovery if the interests of national security or foreign policy so require, or if necessary to comply with...

24 CFR 26.42 - Discovery.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 26.42 Section 26.42... PROCEDURES Hearings Pursuant to the Administrative Procedure Act Discovery § 26.42 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery procedures, which may commence at any time...

49 CFR 386.37 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Discovery. 386.37 Section 386.37 Transportation... and Hearings § 386.37 Discovery. (a) Parties may obtain discovery by one or more of the following...; and requests for admission. (b) Discovery may not commence until the matter is pending before the...

29 CFR 1955.32 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Discovery. 1955.32 Section 1955.32 Labor Regulations...) PROCEDURES FOR WITHDRAWAL OF APPROVAL OF STATE PLANS Preliminary Conference and Discovery § 1955.32 Discovery... allow discovery by any other appropriate procedure, such as by interrogatories upon a party or request...

42 CFR 426.432 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Discovery. 426.432 Section 426.432 Public Health... § 426.432 Discovery. (a) General rule. If the ALJ orders discovery, the ALJ must establish a reasonable timeframe for discovery. (b) Protective order—(1) Request for a protective order. Any party receiving a...

10 CFR 13.21 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Discovery. 13.21 Section 13.21 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) The following types of discovery are...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...

49 CFR 1121.2 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Discovery. 1121.2 Section 1121.2 Transportation... TRANSPORTATION RULES OF PRACTICE RAIL EXEMPTION PROCEDURES § 1121.2 Discovery. Discovery shall follow the procedures set forth at 49 CFR part 1114, subpart B. Discovery may begin upon the filing of the petition for...

38 CFR 42.21 - Discovery.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Discovery. 42.21 Section... IMPLEMENTING THE PROGRAM FRAUD CIVIL REMEDIES ACT § 42.21 Discovery. (a) The following types of discovery are... creation of a document. (c) Unless mutually agreed to by the parties, discovery is available only as...

22 CFR 521.21 - Discovery.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Discovery. 521.21 Section 521.21 Foreign... Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for... interpreted to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...

31 CFR 10.71 - Discovery.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 10.71 Section 10.71 Money... SERVICE Rules Applicable to Disciplinary Proceedings § 10.71 Discovery. (a) In general. Discovery may be... relevance, materiality and reasonableness of the requested discovery and subject to the requirements of § 10...

39 CFR 955.15 - Discovery.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Discovery. 955.15 Section 955.15 Postal Service... APPEALS § 955.15 Discovery. (a) The parties are encouraged to engage in voluntary discovery procedures. In connection with any deposition or other discovery procedure, the Board may issue any order which justice...

43 CFR 35.21 - Discovery.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery. 35.21 Section 35.21 Public... AND STATEMENTS § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...

15 CFR 766.9 - Discovery.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 766.9 Section 766.9... PROCEEDINGS § 766.9 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery... provisions of the Federal Rules of Civil Procedure relating to discovery apply to the extent consistent with...

13 CFR 134.213 - Discovery.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Discovery. 134.213 Section 134.213... OFFICE OF HEARINGS AND APPEALS Rules of Practice for Most Cases § 134.213 Discovery. (a) Motion. A party may obtain discovery only upon motion, and for good cause shown. (b) Forms. The forms of discovery...

31 CFR 16.21 - Discovery.

Science.gov (United States)

2010-07-01

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

How to make guided discovery learning practical for student teachers

NARCIS (Netherlands)

Janssen, F.J.J.M.; Westbroek, H.B.; Van Driel, J.H.

2013-01-01

Many innovative teaching approaches lack classroom impact because teachers consider the proposals impractical. Making a teaching approach practical requires instrumentality (procedures), congruence (local fit), and affordable cost (limited time and resources).This paper concerns a study on the

Journey from discovery of nuclear fission to accelerator-driven sub-critical reactor systems (ADS)

International Nuclear Information System (INIS)

Kapoor, S.S.

2005-01-01

The epoch making discovery of nuclear fission in 1939, which resulted purely from the curiosity driven basic research to understand the atomic and nuclear structure has changed the world forever with the onset of a new era in the history of human civilization. The basic nuclear physics research pursued after the discovery of fission has also been of much relevance in the harnessing of nuclear energy. In the recent years, there is considerable interest towards developing accelerator driven sub-critical reactor systems (ADS) for the incineration of the long-lived spent fuel radioactive waste and for the utilization of thorium fuel for nuclear power generation. In this talk, we discuss important milestones in the journey from discovery of nuclear fission to ADS. (author)

Open source drug discovery--a new paradigm of collaborative research in tuberculosis drug development.

Science.gov (United States)

Bhardwaj, Anshu; Scaria, Vinod; Raghava, Gajendra Pal Singh; Lynn, Andrew Michael; Chandra, Nagasuma; Banerjee, Sulagna; Raghunandanan, Muthukurussi V; Pandey, Vikas; Taneja, Bhupesh; Yadav, Jyoti; Dash, Debasis; Bhattacharya, Jaijit; Misra, Amit; Kumar, Anil; Ramachandran, Srinivasan; Thomas, Zakir; Brahmachari, Samir K

2011-09-01

It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery. Copyright © 2011 Elsevier Ltd. All rights reserved.

Decades of Discovery

Science.gov (United States)

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 and the atom

International Nuclear Information System (INIS)

1989-01-01

''Discovery and the Atom'' tells the story of the founding of nuclear physics. This programme looks at nuclear physics up to the discovery of the neutron in 1932. Animation explains the science of the classic experiments, such as the scattering of alpha particles by Rutherford and the discovery of the nucleus. Archive film shows the people: Lord Rutherford, James Chadwick, Marie Curie. (author)

29 CFR 2700.56 - Discovery; general.

Science.gov (United States)

2010-07-01

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

Preference vs. Authority: A Comparison of Student Searching in a Subject-Specific Indexing and Abstracting Database and a Customized Discovery Layer

Science.gov (United States)

Dahlen, Sarah P. C.; Hanson, Kathlene

2017-01-01

Discovery layers provide a simplified interface for searching library resources. Libraries with limited finances make decisions about retaining indexing and abstracting databases when similar information is available in discovery layers. These decisions should be informed by student success at finding quality information as well as satisfaction…

Dynamic Docking: A Paradigm Shift in Computational Drug Discovery

Directory of Open Access Journals (Sweden)

Dario Gioia

2017-11-01

Full Text Available Molecular docking is the methodology of choice for studying in silico protein-ligand binding and for prioritizing compounds to discover new lead candidates. Traditional docking simulations suffer from major limitations, mostly related to the static or semi-flexible treatment of ligands and targets. They also neglect solvation and entropic effects, which strongly limits their predictive power. During the last decade, methods based on full atomistic molecular dynamics (MD have emerged as a valid alternative for simulating macromolecular complexes. In principle, compared to traditional docking, MD allows the full exploration of drug-target recognition and binding from both the mechanistic and energetic points of view (dynamic docking. Binding and unbinding kinetic constants can also be determined. While dynamic docking is still too computationally expensive to be routinely used in fast-paced drug discovery programs, the advent of faster computing architectures and advanced simulation methodologies are changing this scenario. It is feasible that dynamic docking will replace static docking approaches in the near future, leading to a major paradigm shift in in silico drug discovery. Against this background, we review the key achievements that have paved the way for this progress.

Recent advances in combinatorial biosynthesis for drug discovery

Directory of Open Access Journals (Sweden)

Sun H

2015-02-01

Full Text Available Huihua Sun,1,* Zihe Liu,1,* Huimin Zhao,1,2 Ee Lui Ang1 1Metabolic Engineering Research Laboratory, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, Singapore; 2Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA *These authors contributed equally to this work Abstract: Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel “unnatural” natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1 precursor-directed biosynthesis; 2 enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3 pathway-level recombination. Recent examples of combinatorial biosynthesis employing these

Discovery Monday - Behind the plug: communication networks

CERN Multimedia

2004-01-01

Ever wondered what happens to your email when you click "send"? And when you make a phone call, how does your voice travel down the wire? Find out more about communication networks and their applications at the next Discovery Monday in Microcosm on 1 March. At CERN, networks are used for a multitude of reasons. Mobile phones, for example, are used in the laboratory's underground areas. Optical fibre cabling ensures that CERN's computers are connected to the rest of the world. But how do optical fibres work and what does the future have in store? CERN's experiments also need networks. Particle detectors are made of many layers, each relays complex information to a computer analysis centre which reconstitutes the passage of the particles resulting from collisions. Many billions of bytes are transmitted every second from a multitude of sources, to many computers.  No single computer can handle such a huge flow of information. The next Discovery Monday is your chance to find out how this works.  Participate i...

Panorama 2015 - New conventional oil and gas discoveries

International Nuclear Information System (INIS)

Hureau, Geoffroy; Vially, Roland

2014-12-01

Exploration expenditure rose sharply in 2013, as in the previous year. The overall results for 2014 are likely to show more modest growth at around 5%. In ten years, exploration budgets have increased fivefold, which has led to some major discoveries; but since 2010, the volumes discovered have fallen every year despite the continuing increase in spending. In 2013, 17 billion barrels of oil equivalent (Gboe) were discovered. This is less than both the amount for the previous year and the ten-year average. The initial estimates for 2014 suggest a stabilization of volumes discovered at the same level as 2013. The continuing decline in offshore discoveries in Brazil and East Africa, where operators have cut back on their exploration programmes, appears to have been partly offset by the increase in border areas, such as the pre-salt reservoirs in West Africa and the Russian Arctic. (authors)

Computer-aided drug discovery [v1; ref status: indexed, http://f1000r.es/5ij

Directory of Open Access Journals (Sweden)

Jürgen Bajorath

2015-08-01

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

What Makes Children Defy Majorities? The Role of Dissenters in Chinese and Spanish Preschoolers' Social Judgments.

Science.gov (United States)

Enesco, Ileana; Sebastián-Enesco, Carla; Guerrero, Silvia; Quan, Siyu; Garijo, Sonia

2016-01-01

When many people say the same thing, the individual is more likely to endorse this information than when just a single person says the same. Yet, the influence of consensus information may be modulated by many personal, contextual and cultural variables. Here, we study the sensitivity of Chinese ( N = 68) and Spanish ( N = 82) preschoolers to consensus in social decision making contexts. Children faced two different types of peer-interaction events, which involved (1) uncertain or ambiguous scenarios open to interpretation (social interpretation context), and (2) explicit scenarios depicting the exclusion of a peer (moral judgment context). Children first observed a video in which a group of teachers offered their opinion about the events, and then they were asked to evaluate the information provided. Participants were assigned to two conditions that differed in the type of consensus: Unanimous majority ( non-dissenter condition) and non-unanimous majority ( dissenter condition). In the dissenter condition, we presented the conflicting opinions of three teachers vs. one teacher. In the non-dissenter condition, we presented the unanimous opinion of three teachers. The general results indicated that children's sensitivity to consensus varies depending both on the degree of ambiguity of the social events and the presence or not of a dissenter: (1) Children were much more likely to endorse the majority view when they were uncertain (social interpretation context), than when they already had a clear interpretation of the situation (moral judgment context); (2) The presence of a dissenter resulted in a significant decrease in children's confidence in majority. Interestingly, in the moral judgment context, Chinese and Spanish children differed in their willingness to defy a majority whose opinion run against their own. While Spanish children maintained their own criteria regardless of the type of condition, Chinese children did so when an "allied" dissenter was present

What makes children defy majorities? The role of dissenters in Chinese and Spanish preschoolers’ social judgments.

Directory of Open Access Journals (Sweden)

Ileana Enesco

2016-10-01

Full Text Available When many people say the same thing, the individual is more likely to endorse this information than when just a single person says the same. Yet, the influence of consensus information may be modulated by many personal, contextual and cultural variables. Here, we study the sensitivity of Chinese (N = 68 and Spanish (N = 82 preschoolers to consensus in social decision making contexts. Children faced two different types of peer-interaction events, which involved (1 uncertain or ambiguous scenarios open to interpretation (social interpretation context, and (2 explicit scenarios depicting the exclusion of a peer (moral judgment context. Children first observed a video in which a group of teachers offered their opinion about the events, and then they were asked to evaluate the information provided. Participants were assigned to two conditions that differed in the type of consensus: Unanimous majority (non-dissenter condition and non-unanimous majority (dissenter condition. In the dissenter condition, we presented the conflicting opinions of three teachers vs. one teacher. In the non-dissenter condition, we presented the unanimous opinion of three teachers. The general results indicated that children’s sensitivity to consensus varies depending both on the degree of ambiguity of the social events and the presence or not of a dissenter: 1 Children were much more likely to endorse the majority view when they were uncertain (social interpretation context, than when they already had a clear interpretation of the situation (moral judgment context; 2 The presence of a dissenter resulted in a significant decrease in children’s confidence in majority. Interestingly, in the moral judgment context, Chinese and Spanish children differed in their willingness to defy a majority whose opinion run against their own. While Spanish children maintained their own criteria regardless of the type of condition, Chinese children did so when an allied dissenter was

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

Science.gov (United States)

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.…

A multi-protocol framework for ad-hoc service discovery

OpenAIRE

Flores-Cortes, C.; Blair, Gordon S.; Grace, P.

2006-01-01

Discovering the appropriate services in ad-hoc computing environments where a great number of devices and software components collaborate discreetly and provide numerous services is an important challenge. Service discovery protocols make it possible for participating nodes in a network to locate and advertise services with minimum user intervention. However, because it is not possible to predict at design time which protocols will be used to advertise services in a given context/environment,...

Beijing's nuclear strategy makes China a major player

International Nuclear Information System (INIS)

Bernstein, J.

1988-01-01

This article discusses China's nuclear strategy which is a subject of debate among Asia experts, even as Sino-Soviet relations warm to a point unseen since the 1950s. China lags in the number and sophistication of its weapons. But modernization, national pride and the shrinking U.S. and Soviet arsenals have made Beijing and an increasingly important player. Beijing insists that its arsenal is strictly for defensive purposes; they have signed an agreement to make the South Pacific a nuclear-free zone

29 CFR 2200.208 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Discovery. 2200.208 Section 2200.208 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION RULES OF PROCEDURE Simplified Proceedings § 2200.208 Discovery. Discovery, including requests for admissions, will only be...

47 CFR 65.105 - Discovery.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Discovery. 65.105 Section 65.105... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Procedures § 65.105 Discovery. (a) Participants... evidence. (c) Discovery requests pursuant to § 65.105(b), including written interrogatories, shall be filed...

49 CFR 209.313 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Discovery. 209.313 Section 209.313 Transportation... TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Disqualification Procedures § 209.313 Discovery. (a... parties. Discovery is designed to enable a party to obtain relevant information needed for preparation of...

Quantifying the Ease of Scientific Discovery.

Science.gov (United States)

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.

15 CFR 280.210 - Discovery.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discovery. 280.210 Section 280.210... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE ACCREDITATION AND ASSESSMENT PROGRAMS FASTENER QUALITY Enforcement § 280.210 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery...

PolarHub: A Global Hub for Polar Data Discovery

Science.gov (United States)

Li, W.

2014-12-01

This paper reports the outcome of a NSF project in developing a large-scale web crawler PolarHub to discover automatically the distributed polar dataset in the format of OGC web services (OWS) in the cyberspace. PolarHub is a machine robot; its goal is to visit as many webpages as possible to find those containing information about polar OWS, extract this information and store it into the backend data repository. This is a very challenging task given huge data volume of webpages on the Web. Three unique features was introduced in PolarHub to make it distinctive from earlier crawler solutions: (1) a multi-task, multi-user, multi-thread support to the crawling tasks; (2) an extensive use of thread pool and Data Access Object (DAO) design patterns to separate persistent data storage and business logic to achieve high extendibility of the crawler tool; (3) a pattern-matching based customizable crawling algorithm to support discovery of multi-type geospatial web services; and (4) a universal and portable client-server communication mechanism combining a server-push and client pull strategies for enhanced asynchronous processing. A series of experiments were conducted to identify the impact of crawling parameters to the overall system performance. The geographical distribution pattern of all PolarHub identified services is also demonstrated. We expect this work to make a major contribution to the field of geospatial information retrieval and geospatial interoperability, to bridge the gap between data provider and data consumer, and to accelerate polar science by enhancing the accessibility and reusability of adequate polar data.

10 CFR 1013.21 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Discovery. 1013.21 Section 1013.21 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) PROGRAM FRAUD CIVIL REMEDIES AND PROCEDURES § 1013.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...

37 CFR 2.120 - Discovery.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Discovery. 2.120 Section 2... COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Procedure in Inter Partes Proceedings § 2.120 Discovery. (a... to disclosure and discovery shall apply in opposition, cancellation, interference and concurrent use...

46 CFR 550.502 - Discovery.

Science.gov (United States)

2010-10-01

... 46 Shipping 9 2010-10-01 2010-10-01 false Discovery. 550.502 Section 550.502 Shipping FEDERAL... Proceedings § 550.502 Discovery. The Commission may authorize a party to a proceeding to use depositions, written interrogatories, and discovery procedures that, to the extent practicable, are in conformity with...

15 CFR 785.8 - Discovery.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 785.8 Section 785.8... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter, not...

22 CFR 35.21 - Discovery.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Discovery. 35.21 Section 35.21 Foreign Relations DEPARTMENT OF STATE CLAIMS AND STOLEN PROPERTY PROGRAM FRAUD CIVIL REMEDIES § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

45 CFR 96.65 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 96.65 Section 96.65 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Hearing Procedure § 96.65 Discovery. The use of interrogatories, depositions, and other forms of discovery shall not be allowed. ...

49 CFR 31.21 - Discovery.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Discovery. 31.21 Section 31.21 Transportation Office of the Secretary of Transportation PROGRAM FRAUD CIVIL REMEDIES § 31.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and...

43 CFR 4.1130 - Discovery methods.

Science.gov (United States)

2010-10-01

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

ACFIS: a web server for fragment-based drug discovery

Science.gov (United States)

Hao, Ge-Fei; Jiang, Wen; Ye, Yuan-Nong; Wu, Feng-Xu; Zhu, Xiao-Lei; Guo, Feng-Biao; Yang, Guang-Fu

2016-01-01

In order to foster innovation and improve the effectiveness of drug discovery, there is a considerable interest in exploring unknown ‘chemical space’ to identify new bioactive compounds with novel and diverse scaffolds. Hence, fragment-based drug discovery (FBDD) was developed rapidly due to its advanced expansive search for ‘chemical space’, which can lead to a higher hit rate and ligand efficiency (LE). However, computational screening of fragments is always hampered by the promiscuous binding model. In this study, we developed a new web server Auto Core Fragment in silico Screening (ACFIS). It includes three computational modules, PARA_GEN, CORE_GEN and CAND_GEN. ACFIS can generate core fragment structure from the active molecule using fragment deconstruction analysis and perform in silico screening by growing fragments to the junction of core fragment structure. An integrated energy calculation rapidly identifies which fragments fit the binding site of a protein. We constructed a simple interface to enable users to view top-ranking molecules in 2D and the binding mode in 3D for further experimental exploration. This makes the ACFIS a highly valuable tool for drug discovery. The ACFIS web server is free and open to all users at http://chemyang.ccnu.edu.cn/ccb/server/ACFIS/. PMID:27150808

6 CFR 13.21 - Discovery.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Discovery. 13.21 Section 13.21 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) In general. (1) The following types of discovery are authorized: (i) Requests for production of...

45 CFR 99.23 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 99.23 Section 99.23 Public Welfare... DEVELOPMENT FUND Hearing Procedures § 99.23 Discovery. The Department, the Lead Agency, and any individuals or groups recognized as parties shall have the right to conduct discovery (including depositions) against...

20 CFR 355.21 - Discovery.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Discovery. 355.21 Section 355.21 Employees... UNDER THE PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 355.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...

10 CFR 2.1018 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Discovery. 2.1018 Section 2.1018 Energy NUCLEAR REGULATORY... Geologic Repository § 2.1018 Discovery. (a)(1) Parties, potential parties, and interested governmental participants in the high-level waste licensing proceeding may obtain discovery by one or more of the following...

28 CFR 71.21 - Discovery.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Discovery. 71.21 Section 71.21 Judicial... REMEDIES ACT OF 1986 Implementation for Actions Initiated by the Department of Justice § 71.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

13 CFR 134.310 - Discovery.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Discovery. 134.310 Section 134.310 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION RULES OF PROCEDURE GOVERNING CASES BEFORE THE... Designations § 134.310 Discovery. Discovery will not be permitted in appeals from size determinations or NAICS...

34 CFR 33.21 - Discovery.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 33.21 Section 33.21 Education Office of the Secretary, Department of Education PROGRAM FRAUD CIVIL REMEDIES ACT § 33.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying...

28 CFR 18.7 - Discovery.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Discovery. 18.7 Section 18.7 Judicial Administration DEPARTMENT OF JUSTICE OFFICE OF JUSTICE PROGRAMS HEARING AND APPEAL PROCEDURES § 18.7 Discovery.... Such order may be entered upon a showing that the deposition is necessary for discovery purposes, and...

7 CFR 1.322 - Discovery.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Discovery. 1.322 Section 1.322 Agriculture Office of... Under the Program Fraud Civil Remedies Act of 1986 § 1.322 Discovery. (a) The following types of discovery are authorized: (1) Requests for production, inspection and photocopying of documents; (2...

45 CFR 1386.103 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Discovery. 1386.103 Section 1386.103 Public... Hearing Procedures § 1386.103 Discovery. The Department and any party named in the Notice issued pursuant to § 1386.90 has the right to conduct discovery (including depositions) against opposing parties as...

45 CFR 79.21 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 79.21 Section 79.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

12 CFR 308.520 - Discovery.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Discovery. 308.520 Section 308.520 Banks and... PROCEDURE Program Fraud Civil Remedies and Procedures § 308.520 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...

47 CFR 1.729 - Discovery.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Discovery. 1.729 Section 1.729..., and Reports Involving Common Carriers Formal Complaints § 1.729 Discovery. (a) Subject to paragraph (i... seek discovery of any non-privileged matter that is relevant to the material facts in dispute in the...

7 CFR 283.12 - Discovery.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Discovery. 283.12 Section 283.12 Agriculture... of $50,000 or More § 283.12 Discovery. (a) Dispositions—(1) Motion for taking deposition. Only upon a... exist if the information sought appears reasonably calculated to lead to the discovery of admissible...

Making "Nature" the history of a scientific journal

CERN Document Server

Baldwin, Melinda

2015-01-01

Making "Nature" is the first book to chronicle the foundation and development of Nature, one of the world's most influential scientific institutions. Now nearing its hundred and fiftieth year of publication, Nature is the international benchmark for scientific publication. Its contributors include Charles Darwin, Ernest Rutherford, and Stephen Hawking, and it has published many of the most important discoveries in the history of science, including articles on the structure of DNA, the discovery of the neutron, the first cloning of a mammal, and the human genome. But how did Nature become such an essential institution? In Making "Nature," Melinda Baldwin charts the rich history of this extraordinary publication from its foundation in 1869 to current debates about online publishing and open access. This pioneering study not only tells Nature's story but also sheds light on much larger questions about the history of science publishing, changes in scientific communication, and shifting notions of "scientific comm...

Network-based approaches to climate knowledge discovery

Science.gov (United States)

Budich, Reinhard; Nyberg, Per; Weigel, Tobias

2011-11-01

Climate Knowledge Discovery Workshop; Hamburg, Germany, 30 March to 1 April 2011 Do complex networks combined with semantic Web technologies offer the next generation of solutions in climate science? To address this question, a first Climate Knowledge Discovery (CKD) Workshop, hosted by the German Climate Computing Center (Deutsches Klimarechenzentrum (DKRZ)), brought together climate and computer scientists from major American and European laboratories, data centers, and universities, as well as representatives from industry, the broader academic community, and the semantic Web communities. The participants, representing six countries, were concerned with large-scale Earth system modeling and computational data analysis. The motivation for the meeting was the growing problem that climate scientists generate data faster than it can be interpreted and the need to prepare for further exponential data increases. Current analysis approaches are focused primarily on traditional methods, which are best suited for large-scale phenomena and coarse-resolution data sets. The workshop focused on the open discussion of ideas and technologies to provide the next generation of solutions to cope with the increasing data volumes in climate science.

29 CFR 1603.210 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Discovery. 1603.210 Section 1603.210 Labor Regulations... GOVERNMENT EMPLOYEE RIGHTS ACT OF 1991 Hearings § 1603.210 Discovery. (a) Unless otherwise ordered by the administrative law judge, discovery may begin as soon as the complaint has been transmitted to the administrative...

45 CFR 150.435 - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 150.435 Section 150.435 Public Welfare... AND INDIVIDUAL INSURANCE MARKETS Administrative Hearings § 150.435 Discovery. (a) The parties must identify any need for discovery from the opposing party as soon as possible, but no later than the time for...

34 CFR 81.16 - Discovery.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 81.16 Section 81.16 Education Office of the... Discovery. (a) The parties to a case are encouraged to exchange relevant documents and information voluntarily. (b) The ALJ, at a party's request, may order compulsory discovery described in paragraph (c) of...

29 CFR 1905.25 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 5 2010-07-01 2010-07-01 false Discovery. 1905.25 Section 1905.25 Labor Regulations... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Hearings § 1905.25 Discovery. (a) Depositions. (1) For reasons of... discovery. Whenever appropriate to a just disposition of any issue in a hearing, the presiding hearing...

12 CFR 1780.26 - Discovery.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Discovery. 1780.26 Section 1780.26 Banks and... OF PRACTICE AND PROCEDURE RULES OF PRACTICE AND PROCEDURE Prehearing Proceedings § 1780.26 Discovery. (a) Limits on discovery. Subject to the limitations set out in paragraphs (b), (d), and (e) of this...

42 CFR 430.86 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Discovery. 430.86 Section 430.86 Public Health... Plans and Practice to Federal Requirements § 430.86 Discovery. CMS and any party named in the notice issued under § 430.70 has the right to conduct discovery (including depositions) against opposing parties...

Laboratory informatics tools integration strategies for drug discovery: integration of LIMS, ELN, CDS, and SDMS.

Science.gov (United States)

Machina, Hari K; Wild, David J

2013-04-01

There are technologies on the horizon that could dramatically change how informatics organizations design, develop, deliver, and support applications and data infrastructures to deliver maximum value to drug discovery organizations. Effective integration of data and laboratory informatics tools promises the ability of organizations to make better informed decisions about resource allocation during the drug discovery and development process and for more informed decisions to be made with respect to the market opportunity for compounds. We propose in this article a new integration model called ELN-centric laboratory informatics tools integration.

[The history of the Science of Stress: From Hans Selye to the discovery of anti-inflammatory medication].

Science.gov (United States)

Lupien, Sonia

2015-01-01

To make an important scientific discovery that will make history takes a lot of determination, creativity, perseverance and luck! The story behind the discovery of stress and its biological basis is a fascinating one that places Dr. Hans Selye in the forefront. Dr. Selye was a great scientist that taught at the Université de Montréal from 1945 to his death in 1982. Dr. Selye was curious and hard working. He was determined to understand how various disorders can lead to similar physical manifestations, and this interest led him to discover the role of the adrenal glands involved in the stress response and to better understand the effects of glucocorticoids on the body. Today, the science of stress is based on the foundations established by Dr. Selye. In celebration of the 50th anniversary of the Département de psychiatrie de l'Université de Montréal, and the special issue of the Revue Santé Mentale au Québec, this historical review summarizes the discoveries of this great scientist who worked in Quebec.

Preclinical experimental models of drug metabolism and disposition in drug discovery and development

Directory of Open Access Journals (Sweden)

Donglu Zhang

2012-12-01

Full Text Available Drug discovery and development involve the utilization of in vitro and in vivo experimental models. Different models, ranging from test tube experiments to cell cultures, animals, healthy human subjects, and even small numbers of patients that are involved in clinical trials, are used at different stages of drug discovery and development for determination of efficacy and safety. The proper selection and applications of correct models, as well as appropriate data interpretation, are critically important in decision making and successful advancement of drug candidates. In this review, we discuss strategies in the applications of both in vitro and in vivo experimental models of drug metabolism and disposition.

Discovery Driven Growth

DEFF Research Database (Denmark)

Bukh, Per Nikolaj

2009-01-01

Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august......Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august...

42 CFR 405.1037 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Discovery. 405.1037 Section 405.1037 Public Health... Appeals Under Original Medicare (Part A and Part B) Alj Hearings § 405.1037 Discovery. (a) General rules. (1) Discovery is permissible only when CMS or its contractor elects to participate in an ALJ hearing...

42 CFR 93.512 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 93.512 Section 93.512 Public Health... Process § 93.512 Discovery. (a) Request to provide documents. A party may only request another party to...) Responses to a discovery request. Within 30 days of receiving a request for the production of documents, a...

29 CFR 22.21 - Discovery.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Discovery. 22.21 Section 22.21 Labor Office of the Secretary of Labor PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 22.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for inspection and copying; (2) Requests...

Making Information Visible, Accessible, and Understandable: Meta-Data and Registries

National Research Council Canada - National Science Library

Robinson, Clay

2007-01-01

... the interoperability, discovery, and utility of data assets throughout the Department of Defense (DoD). Proper use and understanding of metadata can substantially enhance the utility of data by making it more visible, accessible, and understandable...

Computational methods in drug discovery

Directory of Open Access Journals (Sweden)

Sumudu P. Leelananda

2016-12-01

Full Text Available 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.

Genomic prediction unifies animal and plant breeding programs to form platforms for biological discovery.

Science.gov (United States)

Hickey, John M; Chiurugwi, Tinashe; Mackay, Ian; Powell, Wayne

2017-08-30

The rate of annual yield increases for major staple crops must more than double relative to current levels in order to feed a predicted global population of 9 billion by 2050. Controlled hybridization and selective breeding have been used for centuries to adapt plant and animal species for human use. However, achieving higher, sustainable rates of improvement in yields in various species will require renewed genetic interventions and dramatic improvement of agricultural practices. Genomic prediction of breeding values has the potential to improve selection, reduce costs and provide a platform that unifies breeding approaches, biological discovery, and tools and methods. Here we compare and contrast some animal and plant breeding approaches to make a case for bringing the two together through the application of genomic selection. We propose a strategy for the use of genomic selection as a unifying approach to deliver innovative 'step changes' in the rate of genetic gain at scale.

Superconductivity: 100th anniversary of its discovery and its future

International Nuclear Information System (INIS)

Kitazawa, Koichi

2011-01-01

The past and prospects of the superconducting technology are discussed as a systematic wide technology from the aspects of energy, transport and telecommunication. Superconductivity has unique characteristics, perpetual current, diamagnetism and Josephson effect. Since its discovery 100 years ago, it had taken nearly half a century to elucidate its mechanism and its application has still been restricted only to fields of extreme needs in the technical level. The major reason for the delay has apparently been the 'penalty of cooling', however, it is also due to the fact that a superconducting wire has to be a complex composite in a nanotechnology-processed structure. Also, owing to the discovery of high-temperature superconductors, it has recently become feasible to forecast a promising future of the superconducting technology in a long term. (author)

Making SharePoint® Chemically Aware™.

Science.gov (United States)

Tallapragada, Kartik; Chewning, Joseph; Kombo, David; Ludwick, Beverly

2012-01-12

The use of SharePoint® collaboration software for content management has become a critical part of today's drug discovery process. SharePoint 2010 software has laid a foundation which enables researchers to collaborate and search on various contents. The amount of data generated during a transition of a single compound from preclinical discovery to commercialization can easily range in terabytes, thus there is a greater demand of a chemically aware search algorithm that supplements SharePoint which enables researchers to query for information in a more intuitive and effective way. Thus by supplementing SharePoint with Chemically Aware™ features provides a great value to the pharmaceutical and biotech companies and makes drug discovery more efficient. Using several tools we have integrated SharePoint with chemical, compound, and reaction databases, thereby improving the traditional search engine capability and enhancing the user experience. This paper describes the implementation of a Chemically Aware™ system to supplement SharePoint. A Chemically Aware SharePoint (CASP) allows users to tag documents by drawing a structure and associating it with the related content. It also allows the user to search SharePoint software content and internal/external databases by carrying out substructure, similarity, SMILES, and IUPAC name searches. Building on traditional search, CASP takes SharePoint one step further by providing a intuitive GUI to the researchers to base their search on their knowledge of chemistry than textual search. CASP also provides a way to integrate with other systems, for example a researcher can perform a sub-structure search on pdf documents with embedded molecular entities. A Chemically Aware™ system supplementing SharePoint is a step towards making drug discovery process more efficient and also helps researchers to search for information in a more intuitive way. It also helps the researchers to find information which was once difficult to find

Making SharePoint® Chemically Aware™

Directory of Open Access Journals (Sweden)

Tallapragada Kartik

2012-01-01

Full Text Available Abstract Background The use of SharePoint® collaboration software for content management has become a critical part of today's drug discovery process. SharePoint 2010 software has laid a foundation which enables researchers to collaborate and search on various contents. The amount of data generated during a transition of a single compound from preclinical discovery to commercialization can easily range in terabytes, thus there is a greater demand of a chemically aware search algorithm that supplements SharePoint which enables researchers to query for information in a more intuitive and effective way. Thus by supplementing SharePoint with Chemically Aware™ features provides a great value to the pharmaceutical and biotech companies and makes drug discovery more efficient. Using several tools we have integrated SharePoint with chemical, compound, and reaction databases, thereby improving the traditional search engine capability and enhancing the user experience. Results This paper describes the implementation of a Chemically Aware™ system to supplement SharePoint. A Chemically Aware SharePoint (CASP allows users to tag documents by drawing a structure and associating it with the related content. It also allows the user to search SharePoint software content and internal/external databases by carrying out substructure, similarity, SMILES, and IUPAC name searches. Building on traditional search, CASP takes SharePoint one step further by providing a intuitive GUI to the researchers to base their search on their knowledge of chemistry than textual search. CASP also provides a way to integrate with other systems, for example a researcher can perform a sub-structure search on pdf documents with embedded molecular entities. Conclusion A Chemically Aware™ system supplementing SharePoint is a step towards making drug discovery process more efficient and also helps researchers to search for information in a more intuitive way. It also helps the

10 CFR 205.198 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Discovery. 205.198 Section 205.198 Energy DEPARTMENT OF... of Proposed Disallowance, and Order of Disallowance § 205.198 Discovery. (a) If a person intends to file a Motion for Discovery, he must file it at the same time that he files his Statement of Objections...

12 CFR 908.46 - Discovery.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Discovery. 908.46 Section 908.46 Banks and... PRACTICE AND PROCEDURE IN HEARINGS ON THE RECORD Pre-Hearing Proceedings § 908.46 Discovery. (a) Limits on discovery. Subject to the limitations set out in paragraphs (b), (d), and (e) of this section, any party to...

21 CFR 17.23 - Discovery.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Discovery. 17.23 Section 17.23 Food and Drugs FOOD... HEARINGS § 17.23 Discovery. (a) No later than 60 days prior to the hearing, unless otherwise ordered by the..., depositions, and any forms of discovery, other than those permitted under paragraphs (a) and (e) of this...

Accessing external innovation in drug discovery and development.

Science.gov (United States)

Tufféry, Pierre

2015-06-01

A decline in the productivity of the pharmaceutical industry research and development (R&D) pipeline has highlighted the need to reconsider the classical strategies of drug discovery and development, which are based on internal resources, and to identify new means to improve the drug discovery process. Accepting that the combination of internal and external ideas can improve innovation, ways to access external innovation, that is, opening projects to external contributions, have recently been sought. In this review, the authors look at a number of external innovation opportunities. These include increased interactions with academia via academic centers of excellence/innovation centers, better communication on projects using crowdsourcing or social media and new models centered on external providers such as built-to-buy startups or virtual pharmaceutical companies. The buzz for accessing external innovation relies on the pharmaceutical industry's major challenge to improve R&D productivity, a conjuncture favorable to increase interactions with academia and new business models supporting access to external innovation. So far, access to external innovation has mostly been considered during early stages of drug development, and there is room for enhancement. First outcomes suggest that external innovation should become part of drug development in the long term. However, the balance between internal and external developments in drug discovery can vary largely depending on the company strategies.

Rediscovering Don Swanson: The Past, Present and Future of Literature-based Discovery

Directory of Open Access Journals (Sweden)

Neil R. Smalheiser

2017-12-01

actually use discovery tools and that these are actually able to help them make experimental discoveries in the lab and in the clinic. Originality/value: This paper discusses problems and issues which were inherent in Don’s thoughts during his life, including those which have not yet been fully taken up and studied systematically.

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

Energy Technology Data Exchange (ETDEWEB)

Wang, Hui; Shi, Tujin; Qian, Wei-Jun; Liu, Tao; Kagan, Jacob; Srivastava, Sudhir; Smith, Richard D.; Rodland, Karin D.; Camp, David G.

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 in LC-MS in the aspect of cancer biomarker discovery and quantification, and discuss its potentials, limitations, and future perspectives.

Celebration of the radium and polonium discovery as a promotion of nuclear energy in Poland

International Nuclear Information System (INIS)

Latek, Stanislaw

1998-01-01

The radium and polonium discovery centennial was inaugurated in April 1997. The first event was a Polish-French show of scientific documentary movies on the uses of ionizing radiation and nuclear power. A symposium Radiation - History and Modern Times was organized in spring 1997. Many other interesting events were held throughout 1997. Warsaw hosted an interesting exhibition 'From the Radium Needle to the Medical Accelerators'. A seminar and an exhibition on Radiation Technique in Environmental Protection were organized in cooperation with the IAEA. The Council for Atomic Energy initiated and conducted a workshop on Radioactivity - Risk and Hope. The Polish Academy of Science and the Society of Nuclear Medicine organised a symposium on Polonium and Radium Discovery Impact on Medicine, Radiation Protection and Medical Industry. The National Atomic Energy was the initiator of film shows held for school youth, which turned out to be a great success. The youngsters, mainly from schools bearing the name of Marie Curie, had an opportunity to see films about the great scientist and her discoveries, and on the very phenomenon of radiation. They also had a chance to visit Maria research reactor in the Institute of Atomic Energy in Swierk. Now, at the beginning of February 1998, a three-day scientific session is being held in Warsaw, to commemorate the radium and polonium discovery. Many other events will take place in the coming months. In particular, June 1998, an international conference on Nuclear Physics Close to the Barriers will be held. Another conference, closing the centennial sponsored by UNESCO will focus on the Scientific and Philosophical Consequences of Discovery of Plutonium and Radium, Benefits and Threats to Mankind. Public opinion polls, similar to those conducted in 1996, are planned for spring 1998. The 1996 polls, conducted 10 years after the Chernobyl accident, showed that the majority of Poles feared ionizing radiation and opposed the nuclear power

The circumstances of minor planet discovery

International Nuclear Information System (INIS)

Pilcher, F.

1989-01-01

The circumstances of discoveries of minor planets are presented in tabular form. Complete data are given for planets 2125-4044, together with notes pertaining to these planets. Information in the table includes the permanent number; the official name; for planets 330 and forward, the table includes the provisional designation attached to the discovery apparition and the year, month, the day of discovery, and the discovery place

The Little Cub: Discovery of an Extremely Metal-poor Star-forming Galaxy in the Local Universe

Energy Technology Data Exchange (ETDEWEB)

Hsyu, Tiffany; Prochaska, J. Xavier; Bolte, Michael [Department of Astronomy and Astrophysics, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060 (United States); Cooke, Ryan J. [Centre for Extragalactic Astronomy, Department of Physics, Durham University, South Road, Durham DH1 3LE (United Kingdom)

2017-08-20

We report the discovery of the Little Cub, an extremely metal-poor star-forming galaxy in the local universe, found in the constellation Ursa Major (a.k.a. the Great Bear). We first identified the Little Cub as a candidate metal-poor galaxy based on its Sloan Digital Sky Survey photometric colors, combined with spectroscopy using the Kast spectrograph on the Shane 3 m telescope at Lick Observatory. In this Letter, we present high-quality spectroscopic data taken with the Low Resolution Imaging Spectrometer at Keck Observatory, which confirm the extremely metal-poor nature of this galaxy. Based on the weak [O iii] λ 4363 Å emission line, we estimate a direct oxygen abundance of 12 + log(O/H) = 7.13 ± 0.08, making the Little Cub one of the lowest-metallicity star-forming galaxies currently known in the local universe. The Little Cub appears to be a companion of the spiral galaxy NGC 3359 and shows evidence of gas stripping. We may therefore be witnessing the quenching of a near-pristine galaxy as it makes its first passage about a Milky Way–like galaxy.

The Little Cub: Discovery of an Extremely Metal-poor Star-forming Galaxy in the Local Universe

Science.gov (United States)

Hsyu, Tiffany; Cooke, Ryan J.; Prochaska, J. Xavier; Bolte, Michael

2017-08-01

We report the discovery of the Little Cub, an extremely metal-poor star-forming galaxy in the local universe, found in the constellation Ursa Major (a.k.a. the Great Bear). We first identified the Little Cub as a candidate metal-poor galaxy based on its Sloan Digital Sky Survey photometric colors, combined with spectroscopy using the Kast spectrograph on the Shane 3 m telescope at Lick Observatory. In this Letter, we present high-quality spectroscopic data taken with the Low Resolution Imaging Spectrometer at Keck Observatory, which confirm the extremely metal-poor nature of this galaxy. Based on the weak [O III] λ4363 Å emission line, we estimate a direct oxygen abundance of 12 + log(O/H) = 7.13 ± 0.08, making the Little Cub one of the lowest-metallicity star-forming galaxies currently known in the local universe. The Little Cub appears to be a companion of the spiral galaxy NGC 3359 and shows evidence of gas stripping. We may therefore be witnessing the quenching of a near-pristine galaxy as it makes its first passage about a Milky Way-like galaxy.

The Little Cub: Discovery of an Extremely Metal-poor Star-forming Galaxy in the Local Universe

International Nuclear Information System (INIS)

Hsyu, Tiffany; Prochaska, J. Xavier; Bolte, Michael; Cooke, Ryan J.

2017-01-01

We report the discovery of the Little Cub, an extremely metal-poor star-forming galaxy in the local universe, found in the constellation Ursa Major (a.k.a. the Great Bear). We first identified the Little Cub as a candidate metal-poor galaxy based on its Sloan Digital Sky Survey photometric colors, combined with spectroscopy using the Kast spectrograph on the Shane 3 m telescope at Lick Observatory. In this Letter, we present high-quality spectroscopic data taken with the Low Resolution Imaging Spectrometer at Keck Observatory, which confirm the extremely metal-poor nature of this galaxy. Based on the weak [O iii] λ 4363 Å emission line, we estimate a direct oxygen abundance of 12 + log(O/H) = 7.13 ± 0.08, making the Little Cub one of the lowest-metallicity star-forming galaxies currently known in the local universe. The Little Cub appears to be a companion of the spiral galaxy NGC 3359 and shows evidence of gas stripping. We may therefore be witnessing the quenching of a near-pristine galaxy as it makes its first passage about a Milky Way–like galaxy.

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

Science.gov (United States)

Drinkwater, Nyssa; McGowan, Sheena

2014-08-01

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

Circuits and electronics hands-on learning with analog discovery

CERN Document Server

Okyere Attia, John

2018-01-01

The book provides instructions on building circuits on breadboards, connecting the Analog Discovery wires to the circuit under test, and making electrical measurements. Various measurement techniques are described and used in this book, including: impedance measurements, complex power measurements, frequency response measurements, power spectrum measurements, current versus voltage characteristic measurements of diodes, bipolar junction transistors, and Mosfets. The book includes end-of-chapter problems for additional exercises geared towards hands-on learning, experimentation, comparisons between measured results and those obtained from theoretical calculations.

Computational Discovery of Materials Using the Firefly Algorithm

Science.gov (United States)

Avendaño-Franco, Guillermo; Romero, Aldo

Our current ability to model physical phenomena accurately, the increase computational power and better algorithms are the driving forces behind the computational discovery and design of novel materials, allowing for virtual characterization before their realization in the laboratory. We present the implementation of a novel firefly algorithm, a population-based algorithm for global optimization for searching the structure/composition space. This novel computation-intensive approach naturally take advantage of concurrency, targeted exploration and still keeping enough diversity. We apply the new method in both periodic and non-periodic structures and we present the implementation challenges and solutions to improve efficiency. The implementation makes use of computational materials databases and network analysis to optimize the search and get insights about the geometric structure of local minima on the energy landscape. The method has been implemented in our software PyChemia, an open-source package for materials discovery. We acknowledge the support of DMREF-NSF 1434897 and the Donors of the American Chemical Society Petroleum Research Fund for partial support of this research under Contract 54075-ND10.

Discovery Monday 'Everyday physics: CERN in my kitchen?'

CERN Multimedia

2005-01-01

Using lasers in the ASACUSA experiment at CERN. As you start imagining menus for the festive season, the next Discovery Monday invites you to think about the physics behind the food you prepare. In fact you may be surprised to find science and technologies used at CERN in many of your dosmestic appliances! Be it the oven used to cook the turkey, the fridge that chills the champagne or the laser in the CD machine you use to play Christmas carols, discover the technologies that make them work and how these same technologies are also applied at CERN. In the case of the CD player, the subject is particularly topical as this year's Nobel Physics Prize was awarded for advances in lasers. Find out more about this and how lasers are used at CERN. In some cases, CERN is developing new technologies that may end up in future domestic appliances, such as the vacuum technology used for flat-screen televisions. After this festive Discovery Monday, join us for a taste of liquid nitrogen ice-cream or a cup of coffee (ma...

EXPERIMENTAL SEMIOTICS: AN ENGINE OF DISCOVERY FOR UNDERSTANDING HUMAN COMMUNICATION

OpenAIRE

BRUNO GALANTUCCI; GARETH ROBERTS

2012-01-01

The recent growth of Experimental Semiotics (ES) offers us a new option to investigate human communication. We briefly introduce ES, presenting results from three themes of research which emerged within it. Then we illustrate the contribution ES can make to the investigation of human communication systems, particularly in comparison with the other existing options. This comparison highlights how ES can provide an engine of discovery for understanding human communication. In fact, in complemen...

mHealth Visual Discovery Dashboard.

Science.gov (United States)

Fang, Dezhi; Hohman, Fred; Polack, Peter; Sarker, Hillol; Kahng, Minsuk; Sharmin, Moushumi; al'Absi, Mustafa; Chau, Duen Horng

2017-09-01

We present Discovery Dashboard, a visual analytics system for exploring large volumes of time series data from mobile medical field studies. Discovery Dashboard offers interactive exploration tools and a data mining motif discovery algorithm to help researchers formulate hypotheses, discover trends and patterns, and ultimately gain a deeper understanding of their data. Discovery Dashboard emphasizes user freedom and flexibility during the data exploration process and enables researchers to do things previously challenging or impossible to do - in the web-browser and in real time. We demonstrate our system visualizing data from a mobile sensor study conducted at the University of Minnesota that included 52 participants who were trying to quit smoking.

The Greatest Mathematical Discovery?

Energy Technology Data Exchange (ETDEWEB)

Bailey, David H.; Borwein, Jonathan M.

2010-05-12

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

A Sensitive Assay for Virus Discovery in Respiratory Clinical Samples

Science.gov (United States)

de Vries, Michel; Deijs, Martin; Canuti, Marta; van Schaik, Barbera D. C.; Faria, Nuno R.; van de Garde, Martijn D. B.; Jachimowski, Loes C. M.; Jebbink, Maarten F.; Jakobs, Marja; Luyf, Angela C. M.; Coenjaerts, Frank E. J.; Claas, Eric C. J.; Molenkamp, Richard; Koekkoek, Sylvie M.; Lammens, Christine; Leus, Frank; Goossens, Herman; Ieven, Margareta; Baas, Frank; van der Hoek, Lia

2011-01-01

In 5–40% of respiratory infections in children, the diagnostics remain negative, suggesting that the patients might be infected with a yet unknown pathogen. Virus discovery cDNA-AFLP (VIDISCA) is a virus discovery method based on recognition of restriction enzyme cleavage sites, ligation of adaptors and subsequent amplification by PCR. However, direct discovery of unknown pathogens in nasopharyngeal swabs is difficult due to the high concentration of ribosomal RNA (rRNA) that acts as competitor. In the current study we optimized VIDISCA by adjusting the reverse transcription enzymes and decreasing rRNA amplification in the reverse transcription, using hexamer oligonucleotides that do not anneal to rRNA. Residual cDNA synthesis on rRNA templates was further reduced with oligonucleotides that anneal to rRNA but can not be extended due to 3′-dideoxy-C6-modification. With these modifications >90% reduction of rRNA amplification was established. Further improvement of the VIDISCA sensitivity was obtained by high throughput sequencing (VIDISCA-454). Eighteen nasopharyngeal swabs were analysed, all containing known respiratory viruses. We could identify the proper virus in the majority of samples tested (11/18). The median load in the VIDISCA-454 positive samples was 7.2 E5 viral genome copies/ml (ranging from 1.4 E3–7.7 E6). Our results show that optimization of VIDISCA and subsequent high-throughput-sequencing enhances sensitivity drastically and provides the opportunity to perform virus discovery directly in patient material. PMID:21283679

A sensitive assay for virus discovery in respiratory clinical samples.

Directory of Open Access Journals (Sweden)

Michel de Vries

Full Text Available In 5-40% of respiratory infections in children, the diagnostics remain negative, suggesting that the patients might be infected with a yet unknown pathogen. Virus discovery cDNA-AFLP (VIDISCA is a virus discovery method based on recognition of restriction enzyme cleavage sites, ligation of adaptors and subsequent amplification by PCR. However, direct discovery of unknown pathogens in nasopharyngeal swabs is difficult due to the high concentration of ribosomal RNA (rRNA that acts as competitor. In the current study we optimized VIDISCA by adjusting the reverse transcription enzymes and decreasing rRNA amplification in the reverse transcription, using hexamer oligonucleotides that do not anneal to rRNA. Residual cDNA synthesis on rRNA templates was further reduced with oligonucleotides that anneal to rRNA but can not be extended due to 3'-dideoxy-C6-modification. With these modifications >90% reduction of rRNA amplification was established. Further improvement of the VIDISCA sensitivity was obtained by high throughput sequencing (VIDISCA-454. Eighteen nasopharyngeal swabs were analysed, all containing known respiratory viruses. We could identify the proper virus in the majority of samples tested (11/18. The median load in the VIDISCA-454 positive samples was 7.2 E5 viral genome copies/ml (ranging from 1.4 E3-7.7 E6. Our results show that optimization of VIDISCA and subsequent high-throughput-sequencing enhances sensitivity drastically and provides the opportunity to perform virus discovery directly in patient material.

Utilization of a major brown rust resistance gene in sugarcane breeding

Science.gov (United States)

Brown rust, caused by Puccinia melanocephala has had devastating effects on sugarcane (Saccharum spp.) breeding programs and on commercial production. The discovery of Bru1, a major gene conferring resistance to brown rust represented a substantial breakthrough and markers for the detection of Bru1 ...

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

Science.gov (United States)

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).

Development of Scientific Approach Based on Discovery Learning Module

Science.gov (United States)

Ellizar, E.; Hardeli, H.; Beltris, S.; Suharni, R.

2018-04-01

Scientific Approach is a learning process, designed to make the students actively construct their own knowledge through stages of scientific method. The scientific approach in learning process can be done by using learning modules. One of the learning model is discovery based learning. Discovery learning is a learning model for the valuable things in learning through various activities, such as observation, experience, and reasoning. In fact, the students’ activity to construct their own knowledge were not optimal. It’s because the available learning modules were not in line with the scientific approach. The purpose of this study was to develop a scientific approach discovery based learning module on Acid Based, also on electrolyte and non-electrolyte solution. The developing process of this chemistry modules use the Plomp Model with three main stages. The stages are preliminary research, prototyping stage, and the assessment stage. The subject of this research was the 10th and 11th Grade of Senior High School students (SMAN 2 Padang). Validation were tested by the experts of Chemistry lecturers and teachers. Practicality of these modules had been tested through questionnaire. The effectiveness had been tested through experimental procedure by comparing student achievement between experiment and control groups. Based on the findings, it can be concluded that the developed scientific approach discovery based learning module significantly improve the students’ learning in Acid-based and Electrolyte solution. The result of the data analysis indicated that the chemistry module was valid in content, construct, and presentation. Chemistry module also has a good practicality level and also accordance with the available time. This chemistry module was also effective, because it can help the students to understand the content of the learning material. That’s proved by the result of learning student. Based on the result can conclude that chemistry module based on

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

Science.gov (United States)

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.

ACFIS: a web server for fragment-based drug discovery.

Science.gov (United States)

Hao, Ge-Fei; Jiang, Wen; Ye, Yuan-Nong; Wu, Feng-Xu; Zhu, Xiao-Lei; Guo, Feng-Biao; Yang, Guang-Fu

2016-07-08

In order to foster innovation and improve the effectiveness of drug discovery, there is a considerable interest in exploring unknown 'chemical space' to identify new bioactive compounds with novel and diverse scaffolds. Hence, fragment-based drug discovery (FBDD) was developed rapidly due to its advanced expansive search for 'chemical space', which can lead to a higher hit rate and ligand efficiency (LE). However, computational screening of fragments is always hampered by the promiscuous binding model. In this study, we developed a new web server Auto Core Fragment in silico Screening (ACFIS). It includes three computational modules, PARA_GEN, CORE_GEN and CAND_GEN. ACFIS can generate core fragment structure from the active molecule using fragment deconstruction analysis and perform in silico screening by growing fragments to the junction of core fragment structure. An integrated energy calculation rapidly identifies which fragments fit the binding site of a protein. We constructed a simple interface to enable users to view top-ranking molecules in 2D and the binding mode in 3D for further experimental exploration. This makes the ACFIS a highly valuable tool for drug discovery. The ACFIS web server is free and open to all users at http://chemyang.ccnu.edu.cn/ccb/server/ACFIS/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Academic Drug Discovery Centres

DEFF Research Database (Denmark)

Kirkegaard, Henriette Schultz; Valentin, Finn

2014-01-01

Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic...

Major Brazilian gold deposits - 1982 to 1999

Science.gov (United States)

Thorman, Charles H.; DeWitt, Ed; Maron, Marcos A.; Ladeira, Eduardo A.

2001-07-01

Brazil has been a major but intermittent producer of gold since its discovery in 1500. Brazil led the world in gold production during the 18th and early 19th centuries. From the late 19th century to the late 20th century, total mining company and garimpeiro production was small and relatively constant at about 5 to 8 t/year. The discovery of alluvial deposits in the Amazon by garimpeiros in the 1970s and the opening of eight mines by mining companies from 1983 to 1990 fueled a major boom in Brazil's gold production, exceeding 100 t/year in 1988 and 1989. However, garimpeiro alluvial production decreased rapidly in the 1990s, to about 10 t/year by 1999. Company production increased about tenfold from about 4 t/year in 1982 to 40 t in 1992. Production from 1992 to the present remained relatively stable, even though several mines were closed or were in the process of closing and no new major mines were put into production during that period. Based on their production history from 1982-1999, 17 gold mines are ranked as major (>20 t) and minor (3-8 t) mines. From 1982-1999, deposits hosted in Archean rocks produced 66% of the gold in Brazil, whereas deposits in Paleoproterozoic and Neoproterozoic rocks accounted for 19% and 15%, respectively. Deposits in metamorphosed sedimentary rocks, especially carbonate-rich rocks and carbonate iron-formation, yielded the great bulk of the gold. Deposits in igneous rocks were of much less importance. The Archean and Paleoproterozoic terranes of Brazil largely lack base-metal-rich volcanogenic massive sulfide deposits, porphyry deposits, and polymetallic veins and sedimentary exhalative deposits. An exception to this is in the Carajás Mineral Province.

Major brazilian gold deposits - 1982 to 1999

Science.gov (United States)

Thorman, C.H.; Dewitt, E.; Maron, M.A.; Ladeira, E.A.

2001-01-01

Brazil has been a major but intermittent producer of gold since its discovery in 1500. Brazil led the world in gold production during the 18th and early 19th centuries. From the late 19th century to the late 20th century, total mining company and garimpeiro production was small and relatively constant at about 5 to 8 t/year. The discovery of alluvial deposits in the Amazon by garimpeiros in the 1970s and the opening of eight mines by mining companies from 1983 to 1990 fueled a major boom in Brazil's gold production, exceeding 100 t/year in 1988 and 1989. However, garimpeiro alluvial production decreased 'rapidly in the 1990s, to about 10 t/year by 1999. Company production increased about tenfold from about 4 t/year in 1982 to 40 t in 1992. Production from 1992 to the present remained relatively stable, even though several mines were closed or were in the process of closing and no new major mines were put into production during that period. Based on their production history from 1982-1999, 17 gold mines are ranked as major (> 20 t) and minor (3-8 t) mines. From 1982-1999, deposits hosted in Archean rocks produced 66% of the gold in Brazil, whereas deposits in Paleoproterozoic and Neoproterozoic rocks accounted for 19% and 15%, respectively. Deposits in metamorphosed sedimentary rocks, especially carbonate-rich rocks and carbonate iron-formation, yielded the great bulk of the gold. Deposits in igneous rocks were of much less importance. The Archean and Paleoproterozoic terranes of Brazil largely lack base-metal-rich volcanogenic massive sulfide deposits, porphyry deposits, and polymetallic veins and sedimentary exhalative deposits. An exception to this is in the Caraja??s Mineral Province.

Twenty years on: the impact of fragments on drug discovery.

Science.gov (United States)

Erlanson, Daniel A; Fesik, Stephen W; Hubbard, Roderick E; Jahnke, Wolfgang; Jhoti, Harren

2016-09-01

After 20 years of sometimes quiet growth, fragment-based drug discovery (FBDD) has become mainstream. More than 30 drug candidates derived from fragments have entered the clinic, with two approved and several more in advanced trials. FBDD has been widely applied in both academia and industry, as evidenced by the large number of papers from universities, non-profit research institutions, biotechnology companies and pharmaceutical companies. Moreover, FBDD draws on a diverse range of disciplines, from biochemistry and biophysics to computational and medicinal chemistry. As the promise of FBDD strategies becomes increasingly realized, now is an opportune time to draw lessons and point the way to the future. This Review briefly discusses how to design fragment libraries, how to select screening techniques and how to make the most of information gleaned from them. It also shows how concepts from FBDD have permeated and enhanced drug discovery efforts.

Serendipity in the Stacks: Libraries, Information Architecture, and the Problems of Accidental Discovery

Science.gov (United States)

Carr, Patrick L.

2015-01-01

Serendipity in the library stacks is generally regarded as a positive occurrence. While acknowledging its benefits, this essay draws on research in library science, information systems, and other fields to argue that, in two important respects, this form of discovery can be usefully framed as a problem. To make this argument, the essay examines…

Microlensing discovery of a population of very tight, very low mass binary brown dwarfs

DEFF Research Database (Denmark)

Choi, J.-Y.; Han, C.; Udalski, A.

2013-01-01

the discovery via gravitational microlensing of two very low mass, very tight binary systems. These binaries have directly and precisely measured total system masses of 0.025 M ☉ and 0.034 M ☉, and projected separations of 0.31 AU and 0.19 AU, making them the lowest-mass and tightest field BD binaries known....... The discovery of a population of such binaries indicates that BD binaries can robustly form at least down to masses of ~0.02 M ☉. Future microlensing surveys will measure a mass-selected sample of BD binary systems, which can then be directly compared to similar samples of stellar binaries....

Synthetic biology of antimicrobial discovery.

Science.gov (United States)

Zakeri, Bijan; Lu, Timothy K

2013-07-19

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

Schizophrenia genomics and proteomics: are we any closer to biomarker discovery?

Directory of Open Access Journals (Sweden)

Kramer Alon

2009-01-01

Full Text Available Abstract The field of proteomics has made leaps and bounds in the last 10 years particularly in the fields of oncology and cardiovascular medicine. In comparison, neuroproteomics is still playing catch up mainly due to the relative complexity of neurological disorders. Schizophrenia is one such disorder, believed to be the results of multiple factors both genetic and environmental. Affecting over 2 million people in the US alone, it has become a major clinical and public health concern worldwide. This paper gives an update of schizophrenia biomarker research as reviewed by Lakhan in 2006 and gives us a rundown of the progress made during the last two years. Several studies demonstrate the potential of cerebrospinal fluid as a source of neuro-specific biomarkers. Genetic association studies are making headway in identifying candidate genes for schizophrenia. In addition, metabonomics, bioinformatics, and neuroimaging techniques are aiming to complete the picture by filling in knowledge gaps. International cooperation in the form of genomics and protein databases and brain banks is facilitating research efforts. While none of the recent developments described here in qualifies as biomarker discovery, many are likely to be stepping stones towards that goal.

Nuclear science in the 20th century. Its historical discoveries and impact on the world: Pt.1

International Nuclear Information System (INIS)

Liu Jun; Xu Furong; Zheng Chunkai; Shen Wenqing

2003-01-01

Nuclear science has been in existence for more than one hundred years, and has affected the world in many important aspects. In this paper, we give a brief overview of the history of nuclear science, including major discoveries such as the discovery of radioactivity, the electron, proton and neutron. The structures of atoms and atomic nuclei are explained, with some historic experiments and theories. The immense impact of nuclear science on the natural sciences and the world is reviewed

Exploring relation types for literature-based discovery.

Science.gov (United States)

Preiss, Judita; Stevenson, Mark; Gaizauskas, Robert

2015-09-01

Literature-based discovery (LBD) aims to identify "hidden knowledge" in the medical literature by: (1) analyzing documents to identify pairs of explicitly related concepts (terms), then (2) hypothesizing novel relations between pairs of unrelated concepts that are implicitly related via a shared concept to which both are explicitly related. Many LBD approaches use simple techniques to identify semantically weak relations between concepts, for example, document co-occurrence. These generate huge numbers of hypotheses, difficult for humans to assess. More complex techniques rely on linguistic analysis, for example, shallow parsing, to identify semantically stronger relations. Such approaches generate fewer hypotheses, but may miss hidden knowledge. The authors investigate this trade-off in detail, comparing techniques for identifying related concepts to discover which are most suitable for LBD. A generic LBD system that can utilize a range of relation types was developed. Experiments were carried out comparing a number of techniques for identifying relations. Two approaches were used for evaluation: replication of existing discoveries and the "time slicing" approach.(1) RESULTS: Previous LBD discoveries could be replicated using relations based either on document co-occurrence or linguistic analysis. Using relations based on linguistic analysis generated many fewer hypotheses, but a significantly greater proportion of them were candidates for hidden knowledge. The use of linguistic analysis-based relations improves accuracy of LBD without overly damaging coverage. LBD systems often generate huge numbers of hypotheses, which are infeasible to manually review. Improving their accuracy has the potential to make these systems significantly more usable. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Discovery and progress of direct cardiac reprogramming.

Science.gov (United States)

Kojima, Hidenori; Ieda, Masaki

2017-06-01

Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs). Following our first report of cardiac reprogramming, many researchers, including ourselves, demonstrated an improvement in cardiac reprogramming efficiency, in vivo direct cardiac reprogramming for heart regeneration, and cardiac reprogramming in human cells. However, cardiac reprogramming in human cells and adult fibroblasts remains inefficient, and further efforts are needed. We believe that future research elucidating epigenetic barriers and molecular mechanisms of direct cardiac reprogramming will improve the reprogramming efficiency, and that this new technology has great potential for clinical applications.

The π discovery

International Nuclear Information System (INIS)

Fowler, P.H.

1988-01-01

The paper traces the discovery of the Π meson. The discovery was made by exposure of nuclear emulsions to cosmic radiation at high altitudes, with subsequent scanning of the emulsions for meson tracks. Disintegration of nuclei by a negative meson, and the decay of a Π meson were both observed. Further measurements revealed the mass of the meson. The studies carried out on the origin of the Π-mesons, and their mode of decay, are both described. (U.K.)

Secure neighborhood discovery: A fundamental element for mobile ad hoc networking

DEFF Research Database (Denmark)

Papadimitratos, P.; Poturalski, M.; Schaller, P.

2008-01-01

Pervasive computing systems will likely be deployed in the near future, with the proliferation of wireless devices and the emergence of ad hoc networking as key enablers. Coping with mobility and the volatility of wireless communications in such systems is critical. Neighborhood discovery (ND......) - the discovery of devices directly reachable for communication or in physical proximity - becomes a fundamental requirement and building block for various applications. However, the very nature of wireless mobile networks makes it easy to abuse ND and thereby compromise the overlying protocols and applications....... Thus, providing methods to mitigate this vulnerability and secure ND is crucial. In this article we focus on this problem and provide definitions of neighborhood types and ND protocol properties, as well as a broad classification of attacks. Our ND literature survey reveals that securing ND is indeed...

The Spiral Discovery Network as an Automated General-Purpose Optimization Tool

Directory of Open Access Journals (Sweden)

Adam B. Csapo

2018-01-01

Full Text Available The Spiral Discovery Method (SDM was originally proposed as a cognitive artifact for dealing with black-box models that are dependent on multiple inputs with nonlinear and/or multiplicative interaction effects. Besides directly helping to identify functional patterns in such systems, SDM also simplifies their control through its characteristic spiral structure. In this paper, a neural network-based formulation of SDM is proposed together with a set of automatic update rules that makes it suitable for both semiautomated and automated forms of optimization. The behavior of the generalized SDM model, referred to as the Spiral Discovery Network (SDN, and its applicability to nondifferentiable nonconvex optimization problems are elucidated through simulation. Based on the simulation, the case is made that its applicability would be worth investigating in all areas where the default approach of gradient-based backpropagation is used today.

Geo-Enrichment and Semantic Enhancement of Metadata Sets to Augment Discovery in Geoportals

Directory of Open Access Journals (Sweden)

Bernhard Vockner

2014-03-01

Full Text Available Geoportals are established to function as main gateways to find, evaluate, and start “using” geographic information. Still, current geoportal implementations face problems in optimizing the discovery process due to semantic heterogeneity issues, which leads to low recall and low precision in performing text-based searches. Therefore, we propose an enhanced semantic discovery approach that supports multilingualism and information domain context. Thus, we present workflow that enriches existing structured metadata with synonyms, toponyms, and translated terms derived from user-defined keywords based on multilingual thesauri and ontologies. To make the results easier and understandable, we also provide automated translation capabilities for the resource metadata to support the user in conceiving the thematic content of the descriptive metadata, even if it has been documented using a language the user is not familiar with. In addition, to text-enable spatial filtering capabilities, we add additional location name keywords to metadata sets. These are based on the existing bounding box and shall tweak discovery scores when performing single text line queries. In order to improve the user’s search experience, we tailor faceted search strategies presenting an enhanced query interface for geo-metadata discovery that are transparently leveraging the underlying thesauri and ontologies.

Hot-spot analysis for drug discovery targeting protein-protein interactions.

Science.gov (United States)

Rosell, Mireia; Fernández-Recio, Juan

2018-04-01

Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.

Synthetic biology of antimicrobial discovery

Science.gov (United States)

Zakeri, Bijan; Lu, Timothy K.

2012-01-01

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

'The Lusiads', poem of discovery

Directory of Open Access Journals (Sweden)

Natasha Furlan Felizi

2016-07-01

Full Text Available The article proposes reading Os Lusíadas as a discovery journey. Discovery here read as aletheia or “revelation”, as proposed by Sophia de Mello Brey­ner Andresen in 1980. Using Martin Heidegger’s notion of aletheia in the book Parmenides along with Jorge de Sena and Sophia de Mello Breyner Andresen reflections on Camões, I’ll seek to point out alternative readings for Os Lusíadas as a “discovery journey”.

Computational methods in drug discovery

OpenAIRE

Sumudu P. Leelananda; Steffen Lindert

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 project...

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

Science.gov (United States)

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…

Investigations into Library Web-Scale Discovery Services

Directory of Open Access Journals (Sweden)

Jason Vaughan

2008-03-01

Full Text Available Web-scale discovery services for libraries provide deep discovery to a library’s local and licensed content, and represent an evolution, perhaps a revolution, for end user information discovery as pertains to library collections.  This article frames the topic of web-scale discovery, and begins by illuminating web-scale discovery from an academic library’s perspective – that is, the internal perspective seeking widespread staff participation in the discovery conversation.  This included the creation of a discovery task force, a group which educated library staff, conducted internal staff surveys, and gathered observations from early adopters.  The article next addresses the substantial research conducted with library vendors which have developed these services.  Such work included drafting of multiple comprehensive question lists distributed to the vendors, onsite vendor visits, and continual tracking of service enhancements.  Together, feedback gained from library staff, insights arrived at by the Discovery Task Force, and information gathered from vendors collectively informed the recommendation of a service for the UNLV Libraries.

The Europa Ocean Discovery mission

Energy Technology Data Exchange (ETDEWEB)

Edwards, B.C. [Los Alamos National Lab., NM (United States); Chyba, C.F. [Univ. of Arizona, Tucson, AZ (United States); Abshire, J.B. [National Aeronautics and Space Administration, Greenbelt, MD (United States). Goddard Space Flight Center] [and others

1997-06-01

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

29 CFR 18.13 - Discovery methods.

Science.gov (United States)

2010-07-01

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

Discovery of the neutron (to the fiftieth anniversary of neutron discovery)

International Nuclear Information System (INIS)

Pasechnik, M.V.

1984-01-01

Development of neutron physics in the USSR for the recent 50 years from the moment of neutron discovery is considered. History of neutron discovery is presented in brief. Neutron properties and fundamental problems of physics: electric dipole neutron moment, neutron β-decay, neutron interaction with nuclei and potential of nucleon interaction not conserving spatial parity are discussed. Main aspects of neutron physics application in power engineering, nuclear technology and other branches of science and technique are set forth

Harvest: a web-based biomedical data discovery and reporting application development platform.

Science.gov (United States)

Italia, Michael J; Pennington, Jeffrey W; Ruth, Byron; Wrazien, Stacey; Loutrel, Jennifer G; Crenshaw, E Bryan; Miller, Jeffrey; White, Peter S

2013-01-01

Biomedical researchers share a common challenge of making complex data understandable and accessible. This need is increasingly acute as investigators seek opportunities for discovery amidst an exponential growth in the volume and complexity of laboratory and clinical data. To address this need, we developed Harvest, an open source framework that provides a set of modular components to aid the rapid development and deployment of custom data discovery software applications. Harvest incorporates visual representations of multidimensional data types in an intuitive, web-based interface that promotes a real-time, iterative approach to exploring complex clinical and experimental data. The Harvest architecture capitalizes on standards-based, open source technologies to address multiple functional needs critical to a research and development environment, including domain-specific data modeling, abstraction of complex data models, and a customizable web client.

41 CFR 60-30.33 - Discovery.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Discovery. 60-30.33... 11246 Expedited Hearing Procedures § 60-30.33 Discovery. (a) Any party may serve requests for admissions... with § 60-30.8, the Administrative Law Judge may allow the taking of depositions. Other discovery will...

Representation Discovery using Harmonic Analysis

CERN Document Server

Mahadevan, Sridhar

2008-01-01

Representations are at the heart of artificial intelligence (AI). This book is devoted to the problem of representation discovery: how can an intelligent system construct representations from its experience? Representation discovery re-parameterizes the state space - prior to the application of information retrieval, machine learning, or optimization techniques - facilitating later inference processes by constructing new task-specific bases adapted to the state space geometry. This book presents a general approach to representation discovery using the framework of harmonic analysis, in particu

Scientific Datasets: Discovery and Aggregation for Semantic Interpretation.

Science.gov (United States)

Lopez, L. A.; Scott, S.; Khalsa, S. J. S.; Duerr, R.

2015-12-01

One of the biggest challenges that interdisciplinary researchers face is finding suitable datasets in order to advance their science; this problem remains consistent across multiple disciplines. A surprising number of scientists, when asked what tool they use for data discovery, reply "Google", which is an acceptable solution in some cases but not even Google can find -or cares to compile- all the data that's relevant for science and particularly geo sciences. If a dataset is not discoverable through a well known search provider it will remain dark data to the scientific world.For the past year, BCube, an EarthCube Building Block project, has been developing, testing and deploying a technology stack capable of data discovery at web-scale using the ultimate dataset: The Internet. This stack has 2 principal components, a web-scale crawling infrastructure and a semantic aggregator. The web-crawler is a modified version of Apache Nutch (the originator of Hadoop and other big data technologies) that has been improved and tailored for data and data service discovery. The second component is semantic aggregation, carried out by a python-based workflow that extracts valuable metadata and stores it in the form of triples through the use semantic technologies.While implementing the BCube stack we have run into several challenges such as a) scaling the project to cover big portions of the Internet at a reasonable cost, b) making sense of very diverse and non-homogeneous data, and lastly, c) extracting facts about these datasets using semantic technologies in order to make them usable for the geosciences community. Despite all these challenges we have proven that we can discover and characterize data that otherwise would have remained in the dark corners of the Internet. Having all this data indexed and 'triplelized' will enable scientists to access a trove of information relevant to their work in a more natural way. An important characteristic of the BCube stack is that all

Portrait of a discovery. Watson, Crick, and the double helix.

Science.gov (United States)

de Chadarevian, Soraya

2003-03-01

This essay examines an iconic image of twentieth-century science: Antony Barrington Brown's photograph of James Watson, Francis Crick, and the double-helical model of DNA. The detailed reconstruction of the production, reception, and uses of the photograph reveals the central role of the image in making the discovery it portrays. Taken in May 1953, two full months after the scientists built the model, to accompany a report on the structure in Time magazine, the photograph (like the report) was never published. It came into circulation only fifteen years later, as an illustration in Watson's best-selling book The Double Helix. While the image served as a historical document and advertisement for the book, only the book provided the description that made the image as well as the people and the model it represented famous. The history of the image provides insights into the retrospective construction of the discovery, which has since been celebrated as the origin of a new science of life.

Antibody informatics for drug discovery

DEFF Research Database (Denmark)

Shirai, Hiroki; Prades, Catherine; Vita, Randi

2014-01-01

to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

45 CFR 213.23a - Discovery.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Discovery. 213.23a Section 213.23a Public Welfare... Discovery. The Department and any party named in the notice issued pursuant to § 213.11 shall have the right to conduct discovery (including depositions) against opposing parties. Rules 26-37 of the Federal...

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

Science.gov (United States)

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.

The use of web ontology languages and other semantic web tools in drug discovery.

Science.gov (United States)

Chen, Huajun; Xie, Guotong

2010-05-01

To optimize drug development processes, pharmaceutical companies require principled approaches to integrate disparate data on a unified infrastructure, such as the web. The semantic web, developed on the web technology, provides a common, open framework capable of harmonizing diversified resources to enable networked and collaborative drug discovery. We survey the state of art of utilizing web ontologies and other semantic web technologies to interlink both data and people to support integrated drug discovery across domains and multiple disciplines. Particularly, the survey covers three major application categories including: i) semantic integration and open data linking; ii) semantic web service and scientific collaboration and iii) semantic data mining and integrative network analysis. The reader will gain: i) basic knowledge of the semantic web technologies; ii) an overview of the web ontology landscape for drug discovery and iii) a basic understanding of the values and benefits of utilizing the web ontologies in drug discovery. i) The semantic web enables a network effect for linking open data for integrated drug discovery; ii) The semantic web service technology can support instant ad hoc collaboration to improve pipeline productivity and iii) The semantic web encourages publishing data in a semantic way such as resource description framework attributes and thus helps move away from a reliance on pure textual content analysis toward more efficient semantic data mining.

Stem cells: a model for screening, discovery and development of drugs.

Science.gov (United States)

Kitambi, Satish Srinivas; Chandrasekar, Gayathri

2011-01-01

The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficacy studies using stem cells offers a reliable platform for the drug discovery process. Advances made in the generation of induced pluripotent stem cells from normal or diseased tissue serves as a platform to perform drug screens aimed at developing cell-based therapies against conditions like Parkinson's disease and diabetes. This review discusses the application of stem cells and cancer stem cells in drug screening and their role in complementing, reducing, and replacing animal testing. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells are also discussed.

Discovery of massive neutral vector mesons

International Nuclear Information System (INIS)

Anon.

1976-01-01

Personal accounts of the discovery of massive neutral vector mesons (psi particles) are given by researchers S. Ting, G. Goldhaber, and B. Richter. The double-arm spectrometer and the Cherenkov effect are explained in a technical note, and the solenoidal magnetic detector is discussed in an explanatory note for nonspecialists. Reprints of three papers in Physical Review Letters which announced the discovery of the particles are given: Experimental observation of a heavy particle J, Discovery of a narrow resonance in e + e - annihilation, and Discovery of a second narrow resonance in e + e - annihilation. A discussion of subsequent developments and scientific biographies of the three authors are also presented. 25 figures

Functional principles of registry-based service discovery

NARCIS (Netherlands)

Sundramoorthy, V.; Tan, C.; Hartel, P.H.; Hartog, den J.I.; Scholten, J.

2005-01-01

As Service Discovery Protocols (SDP) are becoming increasingly important for ubiquitous computing, they must behave according to predefined principles. We present the functional Principles of Service Discovery for robust, registry-based service discovery. A methodology to guarantee adherence to

Data mining workflow templates for intelligent discovery assistance in RapidMiner

OpenAIRE

Kietz, J U; Serban, F; Bernstein, A; Fischer, S

2010-01-01

Knowledge Discovery in Databases (KDD) has evolved during the last years and reached a mature stage offering plenty of operators to solve complex tasks. User support for building workflows, in contrast, has not increased proportionally. The large number of operators available in current KDD systems make it difficult for users to successfully analyze data. Moreover, workflows easily contain a large number of operators and parts of the workflows are applied several times, thus it is hard for us...

Data Mining in Education : A Review on the Knowledge Discovery Perspective

OpenAIRE

Pratiyush Guleria; Manu Sood

2014-01-01

Knowledge Discovery in Databases is the process of finding knowledge in massive amount of data where data mining is the core of this process. Data minin g can be used to mine understandable meaningful patterns from large databases and these patterns ma y then be converted into knowledge.Data mining is t he process of extracting the information and patterns derived by the KDD process which helps in crucial decision-making.Data mining works with data warehou se and...

Materials Discovery | Materials Science | NREL

Science.gov (United States)

Discovery Materials Discovery Images of red and yellow particles NREL's research in materials characterization of sample by incoming beam and measuring outgoing particles, with data being stored and analyzed Staff Scientist Dr. Zakutayev specializes in design of novel semiconductor materials for energy

On the pulse of discovery

Science.gov (United States)

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.

Providing data science support for systems pharmacology and its implications to drug discovery.

Science.gov (United States)

Hart, Thomas; Xie, Lei

2016-01-01

The conventional one-drug-one-target-one-disease drug discovery process has been less successful in tracking multi-genic, multi-faceted complex diseases. Systems pharmacology has emerged as a new discipline to tackle the current challenges in drug discovery. The goal of systems pharmacology is to transform huge, heterogeneous, and dynamic biological and clinical data into interpretable and actionable mechanistic models for decision making in drug discovery and patient treatment. Thus, big data technology and data science will play an essential role in systems pharmacology. This paper critically reviews the impact of three fundamental concepts of data science on systems pharmacology: similarity inference, overfitting avoidance, and disentangling causality from correlation. The authors then discuss recent advances and future directions in applying the three concepts of data science to drug discovery, with a focus on proteome-wide context-specific quantitative drug target deconvolution and personalized adverse drug reaction prediction. Data science will facilitate reducing the complexity of systems pharmacology modeling, detecting hidden correlations between complex data sets, and distinguishing causation from correlation. The power of data science can only be fully realized when integrated with mechanism-based multi-scale modeling that explicitly takes into account the hierarchical organization of biological systems from nucleic acid to proteins, to molecular interaction networks, to cells, to tissues, to patients, and to populations.

Argo_CUDA: Exhaustive GPU based approach for motif discovery in large DNA datasets.

Science.gov (United States)

Vishnevsky, Oleg V; Bocharnikov, Andrey V; Kolchanov, Nikolay A

2018-02-01

The development of chromatin immunoprecipitation sequencing (ChIP-seq) technology has revolutionized the genetic analysis of the basic mechanisms underlying transcription regulation and led to accumulation of information about a huge amount of DNA sequences. There are a lot of web services which are currently available for de novo motif discovery in datasets containing information about DNA/protein binding. An enormous motif diversity makes their finding challenging. In order to avoid the difficulties, researchers use different stochastic approaches. Unfortunately, the efficiency of the motif discovery programs dramatically declines with the query set size increase. This leads to the fact that only a fraction of top "peak" ChIP-Seq segments can be analyzed or the area of analysis should be narrowed. Thus, the motif discovery in massive datasets remains a challenging issue. Argo_Compute Unified Device Architecture (CUDA) web service is designed to process the massive DNA data. It is a program for the detection of degenerate oligonucleotide motifs of fixed length written in 15-letter IUPAC code. Argo_CUDA is a full-exhaustive approach based on the high-performance GPU technologies. Compared with the existing motif discovery web services, Argo_CUDA shows good prediction quality on simulated sets. The analysis of ChIP-Seq sequences revealed the motifs which correspond to known transcription factor binding sites.

Discovery radiomics via evolutionary deep radiomic sequencer discovery for pathologically proven lung cancer detection.

Science.gov (United States)

Shafiee, Mohammad Javad; Chung, Audrey G; Khalvati, Farzad; Haider, Masoom A; Wong, Alexander

2017-10-01

While lung cancer is the second most diagnosed form of cancer in men and women, a sufficiently early diagnosis can be pivotal in patient survival rates. Imaging-based, or radiomics-driven, detection methods have been developed to aid diagnosticians, but largely rely on hand-crafted features that may not fully encapsulate the differences between cancerous and healthy tissue. Recently, the concept of discovery radiomics was introduced, where custom abstract features are discovered from readily available imaging data. We propose an evolutionary deep radiomic sequencer discovery approach based on evolutionary deep intelligence. Motivated by patient privacy concerns and the idea of operational artificial intelligence, the evolutionary deep radiomic sequencer discovery approach organically evolves increasingly more efficient deep radiomic sequencers that produce significantly more compact yet similarly descriptive radiomic sequences over multiple generations. As a result, this framework improves operational efficiency and enables diagnosis to be run locally at the radiologist's computer while maintaining detection accuracy. We evaluated the evolved deep radiomic sequencer (EDRS) discovered via the proposed evolutionary deep radiomic sequencer discovery framework against state-of-the-art radiomics-driven and discovery radiomics methods using clinical lung CT data with pathologically proven diagnostic data from the LIDC-IDRI dataset. The EDRS shows improved sensitivity (93.42%), specificity (82.39%), and diagnostic accuracy (88.78%) relative to previous radiomics approaches.

Discovery of inhibitors of bacterial histidine kinases

NARCIS (Netherlands)

Velikova, N.R.

2014-01-01

Discovery of Inhibitors of Bacterial Histidine Kinases Summary

The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based drug discovery approach, we have identified small-molecule histidine-kinase

The equivalence of learning paths in early science instruction: effect of direct instruction and discovery learning.

Science.gov (United States)

Klahr, David; Nigam, Milena

2004-10-01

In a study with 112 third- and fourth-grade children, we measured the relative effectiveness of discovery learning and direct instruction at two points in the learning process: (a) during the initial acquisition of the basic cognitive objective (a procedure for designing and interpreting simple, unconfounded experiments) and (b) during the subsequent transfer and application of this basic skill to more diffuse and authentic reasoning associated with the evaluation of science-fair posters. We found not only that many more children learned from direct instruction than from discovery learning, but also that when asked to make broader, richer scientific judgments, the many children who learned about experimental design from direct instruction performed as well as those few children who discovered the method on their own. These results challenge predictions derived from the presumed superiority of discovery approaches in teaching young children basic procedures for early scientific investigations.

Cross-pollination of research findings, although uncommon, may accelerate discovery of human disease genes

Directory of Open Access Journals (Sweden)

Duda Marlena

2012-11-01

Full Text Available Abstract Background Technological leaps in genome sequencing have resulted in a surge in discovery of human disease genes. These discoveries have led to increased clarity on the molecular pathology of disease and have also demonstrated considerable overlap in the genetic roots of human diseases. In light of this large genetic overlap, we tested whether cross-disease research approaches lead to faster, more impactful discoveries. Methods We leveraged several gene-disease association databases to calculate a Mutual Citation Score (MCS for 10,853 pairs of genetically related diseases to measure the frequency of cross-citation between research fields. To assess the importance of cooperative research, we computed an Individual Disease Cooperation Score (ICS and the average publication rate for each disease. Results For all disease pairs with one gene in common, we found that the degree of genetic overlap was a poor predictor of cooperation (r2=0.3198 and that the vast majority of disease pairs (89.56% never cited previous discoveries of the same gene in a different disease, irrespective of the level of genetic similarity between the diseases. A fraction (0.25% of the pairs demonstrated cross-citation in greater than 5% of their published genetic discoveries and 0.037% cross-referenced discoveries more than 10% of the time. We found strong positive correlations between ICS and publication rate (r2=0.7931, and an even stronger correlation between the publication rate and the number of cross-referenced diseases (r2=0.8585. These results suggested that cross-disease research may have the potential to yield novel discoveries at a faster pace than singular disease research. Conclusions Our findings suggest that the frequency of cross-disease study is low despite the high level of genetic similarity among many human diseases, and that collaborative methods may accelerate and increase the impact of new genetic discoveries. Until we have a better

Service discovery using Bloom filters

NARCIS (Netherlands)

Goering, P.T.H.; Heijenk, Geert; Lelieveldt, B.P.F.; Haverkort, Boudewijn R.H.M.; de Laat, C.T.A.M.; Heijnsdijk, J.W.J.

A protocol to perform service discovery in adhoc networks is introduced in this paper. Attenuated Bloom filters are used to distribute services to nodes in the neighborhood and thus enable local service discovery. The protocol has been implemented in a discrete event simulator to investigate the

Using concepts in literature-based discovery : Simulating Swanson's Raynaud-fish oil and migraine-magnesium discoveries

NARCIS (Netherlands)

Weeber, M; Klein, Henny; de Jong-van den Berg, LTW; Vos, R

Literature-based discovery has resulted in new knowledge. In the biomedical context, Don R. Swanson has generated several literature-based hypotheses that have been corroborated experimentally and clinically. In this paper, we propose a two-step model of the discovery process in which hypotheses are

12 CFR 747.24 - Scope of document discovery.

Science.gov (United States)

2010-01-01

... act of Congress, or the principles of common law provide. (d) Time limits. All discovery, including... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Scope of document discovery. 747.24 Section 747... of Practice and Procedure § 747.24 Scope of document discovery. (a) Limits on discovery. (1) Subject...

Resource Discovery in Activity-Based Sensor Networks

DEFF Research Database (Denmark)

Bucur, Doina; Bardram, Jakob

This paper proposes a service discovery protocol for sensor networks that is specifically tailored for use in humancentered pervasive environments. It uses the high-level concept of computational activities (as logical bundles of data and resources) to give sensors in Activity-Based Sensor Networ....... ABSN enhances the generic Extended Zone Routing Protocol with logical sensor grouping and greatly lowers network overhead during the process of discovery, while keeping discovery latency close to optimal.......This paper proposes a service discovery protocol for sensor networks that is specifically tailored for use in humancentered pervasive environments. It uses the high-level concept of computational activities (as logical bundles of data and resources) to give sensors in Activity-Based Sensor Networks...... (ABSNs) knowledge about their usage even at the network layer. ABSN redesigns classical network-level service discovery protocols to include and use this logical structuring of the network for a more practically applicable service discovery scheme. Noting that in practical settings activity-based sensor...

Harvest: an open platform for developing web-based biomedical data discovery and reporting applications.

Science.gov (United States)

Pennington, Jeffrey W; Ruth, Byron; Italia, Michael J; Miller, Jeffrey; Wrazien, Stacey; Loutrel, Jennifer G; Crenshaw, E Bryan; White, Peter S

2014-01-01

Biomedical researchers share a common challenge of making complex data understandable and accessible as they seek inherent relationships between attributes in disparate data types. Data discovery in this context is limited by a lack of query systems that efficiently show relationships between individual variables, but without the need to navigate underlying data models. We have addressed this need by developing Harvest, an open-source framework of modular components, and using it for the rapid development and deployment of custom data discovery software applications. Harvest incorporates visualizations of highly dimensional data in a web-based interface that promotes rapid exploration and export of any type of biomedical information, without exposing researchers to underlying data models. We evaluated Harvest with two cases: clinical data from pediatric cardiology and demonstration data from the OpenMRS project. Harvest's architecture and public open-source code offer a set of rapid application development tools to build data discovery applications for domain-specific biomedical data repositories. All resources, including the OpenMRS demonstration, can be found at http://harvest.research.chop.edu.

Novel Technology for Protein-Protein Interaction-based Targeted Drug Discovery

Directory of Open Access Journals (Sweden)

Jung Me Hwang

2011-12-01

Full Text Available We have developed a simple but highly efficient in-cell protein-protein interaction (PPI discovery system based on the translocation properties of protein kinase C- and its C1a domain in live cells. This system allows the visual detection of trimeric and dimeric protein interactions including cytosolic, nuclear, and/or membrane proteins with their cognate ligands. In addition, this system can be used to identify pharmacological small compounds that inhibit specific PPIs. These properties make this PPI system an attractive tool for screening drug candidates and mapping the protein interactome.

Price discovery in a continuous-time setting

DEFF Research Database (Denmark)

Dias, Gustavo Fruet; Fernandes, Marcelo; Scherrer, Cristina

We formulate a continuous-time price discovery model in which the price discovery measure varies (stochastically) at daily frequency. We estimate daily measures of price discovery using a kernel-based OLS estimator instead of running separate daily VECM regressions as standard in the literature. We...... show that our estimator is not only consistent, but also outperforms the standard daily VECM in finite samples. We illustrate our theoretical findings by studying the price discovery process of 10 actively traded stocks in the U.S. from 2007 to 2013....

Defining Creativity with Discovery

OpenAIRE

Wilson, Nicholas Charles; Martin, Lee

2017-01-01

The standard definition of creativity has enabled significant empirical and theoretical advances, yet contains philosophical conundrums concerning the nature of novelty and the role of recognition and values. In this work we offer an act of conceptual valeting that addresses these issues and in doing so, argue that creativity definitions can be extended through the use of discovery. Drawing on dispositional realist philosophy we outline why adding the discovery and bringing into being of new ...

On the antiproton discovery

International Nuclear Information System (INIS)

Piccioni, O.

1989-01-01

The author of this article describes his own role in the discovery of the antiproton. Although Segre and Chamberlain received the Nobel Prize in 1959 for its discovery, the author claims that their experimental method was his idea which he communicated to them informally in December 1954. He describes how his application for citizenship (he was Italian), and other scientists' manipulation, prevented him from being at Berkeley to work on the experiment himself. (UK)

An agent-based peer-to-peer architecture for semantic discovery of manufacturing services across virtual enterprises

Science.gov (United States)

Zhang, Wenyu; Zhang, Shuai; Cai, Ming; Jian, Wu

2015-04-01

With the development of virtual enterprise (VE) paradigm, the usage of serviceoriented architecture (SOA) is increasingly being considered for facilitating the integration and utilisation of distributed manufacturing resources. However, due to the heterogeneous nature among VEs, the dynamic nature of a VE and the autonomous nature of each VE member, the lack of both sophisticated coordination mechanism in the popular centralised infrastructure and semantic expressivity in the existing SOA standards make the current centralised, syntactic service discovery method undesirable. This motivates the proposed agent-based peer-to-peer (P2P) architecture for semantic discovery of manufacturing services across VEs. Multi-agent technology provides autonomous and flexible problemsolving capabilities in dynamic and adaptive VE environments. Peer-to-peer overlay provides highly scalable coupling across decentralised VEs, each of which exhibiting as a peer composed of multiple agents dealing with manufacturing services. The proposed architecture utilises a novel, efficient, two-stage search strategy - semantic peer discovery and semantic service discovery - to handle the complex searches of manufacturing services across VEs through fast peer filtering. The operation and experimental evaluation of the prototype system are presented to validate the implementation of the proposed approach.

Bacterial fatty acid metabolism in modern antibiotic discovery.

Science.gov (United States)

Yao, Jiangwei; Rock, Charles O

2017-11-01

Bacterial fatty acid synthesis is essential for many pathogens and different from the mammalian counterpart. These features make bacterial fatty acid synthesis a desirable target for antibiotic discovery. The structural divergence of the conserved enzymes and the presence of different isozymes catalyzing the same reactions in the pathway make bacterial fatty acid synthesis a narrow spectrum target rather than the traditional broad spectrum target. Furthermore, bacterial fatty acid synthesis inhibitors are single-targeting, rather than multi-targeting like traditional monotherapeutic, broad-spectrum antibiotics. The single-targeting nature of bacterial fatty acid synthesis inhibitors makes overcoming fast-developing, target-based resistance a necessary consideration for antibiotic development. Target-based resistance can be overcome through multi-targeting inhibitors, a cocktail of single-targeting inhibitors, or by making the single targeting inhibitor sufficiently high affinity through a pathogen selective approach such that target-based mutants are still susceptible to therapeutic concentrations of drug. Many of the pathogens requiring new antibiotic treatment options encode for essential bacterial fatty acid synthesis enzymes. This review will evaluate the most promising targets in bacterial fatty acid metabolism for antibiotic therapeutics development and review the potential and challenges in advancing each of these targets to the clinic and circumventing target-based resistance. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.

NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening.

Science.gov (United States)

Thornburg, Christopher C; Britt, John R; Evans, Jason R; Akee, Rhone K; Whitt, James A; Trinh, Spencer K; Harris, Matthew J; Thompson, Jerell R; Ewing, Teresa L; Shipley, Suzanne M; Grothaus, Paul G; Newman, David J; Schneider, Joel P; Grkovic, Tanja; O'Keefe, Barry R

2018-06-13

The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural product discovery technologies and facilitate the discovery of structurally defined, validated lead molecules ready for translation will create a prefractionated library from over 125,000 natural product extracts with the aim of producing a publicly-accessible, HTS-amenable library of >1,000,000 fractions. This library, representing perhaps the largest accumulation of natural-product based fractions in the world, will be made available free of charge in 384-well plates for screening against all disease states in an effort to reinvigorate natural product-based drug discovery.

Resource-estimation models and predicted discovery

International Nuclear Information System (INIS)

Hill, G.W.

1982-01-01

Resources have been estimated by predictive extrapolation from past discovery experience, by analogy with better explored regions, or by inference from evidence of depletion of targets for exploration. Changes in technology and new insights into geological mechanisms have occurred sufficiently often in the long run to form part of the pattern of mature discovery experience. The criterion, that a meaningful resource estimate needs an objective measure of its precision or degree of uncertainty, excludes 'estimates' based solely on expert opinion. This is illustrated by development of error measures for several persuasive models of discovery and production of oil and gas in USA, both annually and in terms of increasing exploration effort. Appropriate generalizations of the models resolve many points of controversy. This is illustrated using two USA data sets describing discovery of oil and of U 3 O 8 ; the latter set highlights an inadequacy of available official data. Review of the oil-discovery data set provides a warrant for adjusting the time-series prediction to a higher resource figure for USA petroleum. (author)

Bringing your tools to CyVerse Discovery Environment using Docker.

Science.gov (United States)

Devisetty, Upendra Kumar; Kennedy, Kathleen; Sarando, Paul; Merchant, Nirav; Lyons, Eric

2016-01-01

Docker has become a very popular container-based virtualization platform for software distribution that has revolutionized the way in which scientific software and software dependencies (software stacks) can be packaged, distributed, and deployed. Docker makes the complex and time-consuming installation procedures needed for scientific software a one-time process. Because it enables platform-independent installation, versioning of software environments, and easy redeployment and reproducibility, Docker is an ideal candidate for the deployment of identical software stacks on different compute environments such as XSEDE and Amazon AWS. CyVerse's Discovery Environment also uses Docker for integrating its powerful, community-recommended software tools into CyVerse's production environment for public use. This paper will help users bring their tools into CyVerse Discovery Environment (DE) which will not only allows users to integrate their tools with relative ease compared to the earlier method of tool deployment in DE but will also help users to share their apps with collaborators and release them for public use.

7 CFR 283.28 - Discovery.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Discovery. 283.28 Section 283.28 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE... Appeals of QC Claims of Less Than $50,000 § 283.28 Discovery. Upon motion and as ordered by the ALJ...

High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes.

Science.gov (United States)

Lorenz, Daniel A; Song, James M; Garner, Amanda L

2015-01-21

MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.

Discovery of charm

International Nuclear Information System (INIS)

Goldhaber, G.

1984-11-01

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

Discovery potential of xenon-based neutrinoless double beta decay experiments in light of small angular scale CMB observations

International Nuclear Information System (INIS)

Gómez-Cadenas, J.J.; Martín-Albo, J.; Vidal, J. Muñoz; Peña-Garay, C.

2013-01-01

The South Pole Telescope (SPT) has probed an expanded angular range of the CMB temperature power spectrum. Their recent analysis of the latest cosmological data prefers nonzero neutrino masses, with Σm ν = (0.32±0.11) eV. This result, if confirmed by the upcoming Planck data, has deep implications on the discovery of the nature of neutrinos. In particular, the values of the effective neutrino mass m ββ involved in neutrinoless double beta decay (ββ0ν) are severely constrained for both the direct and inverse hierarchy, making a discovery much more likely. In this paper, we focus in xenon-based ββ0ν experiments, on the double grounds of their good performance and the suitability of the technology to large-mass scaling. We show that the current generation, with effective masses in the range of 100 kg and conceivable exposures in the range of 500 kg·year, could already have a sizeable opportunity to observe ββ0ν events, and their combined discovery potential is quite large. The next generation, with an exposure in the range of 10 ton·year, would have a much more enhanced sensitivity, in particular due to the very low specific background that all the xenon technologies (liquid xenon, high-pressure xenon and xenon dissolved in liquid scintillator) can achieve. In addition, a high-pressure xenon gas TPC also features superb energy resolution. We show that such detector can fully explore the range of allowed effective Majorana masses, thus making a discovery very likely

Data mining-aided materials discovery and optimization

Directory of Open Access Journals (Sweden)

Wencong Lu

2017-09-01

Full Text Available Recent developments in data mining-aided materials discovery and optimization are reviewed in this paper, and an introduction to the materials data mining (MDM process is provided using case studies. Both qualitative and quantitative methods in machine learning can be adopted in the MDM process to accomplish different tasks in materials discovery, design, and optimization. State-of-the-art techniques in data mining-aided materials discovery and optimization are demonstrated by reviewing the controllable synthesis of dendritic Co3O4 superstructures, materials design of layered double hydroxide, battery materials discovery, and thermoelectric materials design. The results of the case studies indicate that MDM is a powerful approach for use in materials discovery and innovation, and will play an important role in the development of the Materials Genome Initiative and Materials Informatics.

Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) based bioavailability determination of the major classes of phytochemicals.

Science.gov (United States)

Stylos, Evgenios; Chatziathanasiadou, Maria V; Syriopoulou, Aggeliki; Tzakos, Andreas G

2017-03-15

Natural products derived from plants have served as an inexhausted source for drug discovery and drug development. They have been evolutionary amplified with drug-like properties and have already illustrated immense therapeutic potential over an array of different diseases. However, their incorporation in the drug discovery pipeline has been diminished the last two decades. This was probably due to barriers related to their inherent difficulties to be integrated in high-throughput screening assays as also their largely unexplored bioavailability. Analytical procedures have come into the spotlight, a result of the continuous development of the instrumentation's capabilities as far as detection and separation is concerned. Integral part of this technological evolution is LC-MS instrumentation and its extended use for the determination of various compounds. The fact that it provides extra sensitivity, specificity and good separation in complex samples, makes LC-MS/MS the ultimate tool in the determination of many types of chemical compounds, such as phytochemicals. Herein, we focus on the achievements of the last five years in quantitative analysis of the major classes of phytochemicals (flavonoids, alkaloids, terpenes, glycosides and saponins) in plasma, through LC-MS/MS, as also their bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment

Directory of Open Access Journals (Sweden)

Mian Zu

2015-11-01

Full Text Available The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential drug targets due to their distinct advantage of lack of evolution and drug resistance. Cdc2-like kinase 1 (CLK1 in the host cells is responsible for alternative splicing of the M2 gene of influenza virus during influenza infection and replication. In this study, we carried out baculovirus-mediated expression and purification of CLK1 and established a reliable screening assay for CLK1 inhibitors. After a virtual screening of CLK1 inhibitors was performed, the activities of the selected compounds were evaluated. Finally, several compounds with strong inhibitory activity against CLK1 were discovered and their in vitro anti-influenza virus activities were validated using a cytopathic effect (CPE reduction assay. The assay results showed that clypearin, corilagin, and pinosylvine were the most potential anti-influenza virus compounds as CLK1 inhibitors among the compounds tested. These findings will provide important information for new drug design and development in influenza treatment, and CLK1 may be a potent drug target for anti-influenza drug screening and discovery.

12 CFR 509.102 - Discovery.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Discovery. 509.102 Section 509.102 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY RULES OF PRACTICE AND PROCEDURE IN ADJUDICATORY PROCEEDINGS Local Rules § 509.102 Discovery. (a) In general. A party may take the deposition of an...

Maximum Entropy in Drug Discovery

Directory of Open Access Journals (Sweden)

Chih-Yuan Tseng

2014-07-01

Full Text Available Drug discovery applies multidisciplinary approaches either experimentally, computationally or both ways to identify lead compounds to treat various diseases. While conventional approaches have yielded many US Food and Drug Administration (FDA-approved drugs, researchers continue investigating and designing better approaches to increase the success rate in the discovery process. In this article, we provide an overview of the current strategies and point out where and how the method of maximum entropy has been introduced in this area. The maximum entropy principle has its root in thermodynamics, yet since Jaynes’ pioneering work in the 1950s, the maximum entropy principle has not only been used as a physics law, but also as a reasoning tool that allows us to process information in hand with the least bias. Its applicability in various disciplines has been abundantly demonstrated. We give several examples of applications of maximum entropy in different stages of drug discovery. Finally, we discuss a promising new direction in drug discovery that is likely to hinge on the ways of utilizing maximum entropy.

The role of self-blaming moral emotions in major depression and their impact on social-economical decision making

Directory of Open Access Journals (Sweden)

Erdem ePulcu

2013-06-01

Full Text Available People with major depressive disorder (MDD are more prone to experiencing moral emotions related to self-blame, such as guilt and shame. DSM-IV-TR recognises excessive or inappropriate guilt as one of the core symptoms of current MDD, whereas excessive shame is not part of the criteria for MDD. However, previous studies specifically assessing shame suggested its involvement in MDD. In the first part of this review, we will consider literature discussing the role of self-blaming moral emotions in MDD. These self-blaming moral emotions have been purported to influence people when they make social and financial decisions in cognitive studies, particularly those using neuroeconomical paradigms. Such paradigms aim to predict social behaviour in activities of daily living, by using important resource tangibles (especially money in laboratory conditions. Previous literature suggests that guilt promotes altruistic behaviour via acting out reparative tendencies, whereas shame reduces altruism by means of increasing social and interpersonal distance. In the second part of this review, we will discuss the potential influence of self-blaming moral emotions on overt behaviour in MDD, reviewing clinical and experimental studies in social and financial decision-making, in which guilt and shame were manipulated. This is not a well-established area in the depression literature, however in this opinion paper we will argue that studies of moral emotions and their impact on behavioural decision-making are of potential importance in the clinical field, by linking specific symptoms of a disorder to a behavioural outcome which may lead to stratification of clinical diagnoses in the future.

The role of self-blaming moral emotions in major depression and their impact on social-economical decision making.

Science.gov (United States)

Pulcu, Erdem; Zahn, Roland; Elliott, Rebecca

2013-01-01

People with major depressive disorder (MDD) are more prone to experiencing moral emotions related to self-blame, such as guilt and shame. DSM-IV-TR recognizes excessive or inappropriate guilt as one of the core symptoms of current MDD, whereas excessive shame is not part of the criteria for MDD. However, previous studies specifically assessing shame suggested its involvement in MDD. In the first part of this review, we will consider literature discussing the role of self-blaming moral emotions in MDD. These self-blaming moral emotions have been purported to influence people when they make social and financial decisions in cognitive studies, particularly those using neuroeconomical paradigms. Such paradigms aim to predict social behavior in activities of daily living, by using important resource tangibles (especially money) in laboratory conditions. Previous literature suggests that guilt promotes altruistic behavior via acting out reparative tendencies, whereas shame reduces altruism by means of increasing social and interpersonal distance. In the second part of this review, we will discuss the potential influence of self-blaming moral emotions on overt behavior in MDD, reviewing clinical and experimental studies in social and financial decision-making, in which guilt, and shame were manipulated. This is not a well-established area in the depression literature, however in this opinion paper we will argue that studies of moral emotions and their impact on behavioral decision-making are of potential importance in the clinical field, by linking specific symptoms of a disorder to a behavioral outcome which may lead to stratification of clinical diagnoses in the future.

The Role of Self-Blaming Moral Emotions in Major Depression and Their Impact on Social-Economical Decision Making

Science.gov (United States)

Pulcu, Erdem; Zahn, Roland; Elliott, Rebecca

2013-01-01

People with major depressive disorder (MDD) are more prone to experiencing moral emotions related to self-blame, such as guilt and shame. DSM-IV-TR recognizes excessive or inappropriate guilt as one of the core symptoms of current MDD, whereas excessive shame is not part of the criteria for MDD. However, previous studies specifically assessing shame suggested its involvement in MDD. In the first part of this review, we will consider literature discussing the role of self-blaming moral emotions in MDD. These self-blaming moral emotions have been purported to influence people when they make social and financial decisions in cognitive studies, particularly those using neuroeconomical paradigms. Such paradigms aim to predict social behavior in activities of daily living, by using important resource tangibles (especially money) in laboratory conditions. Previous literature suggests that guilt promotes altruistic behavior via acting out reparative tendencies, whereas shame reduces altruism by means of increasing social and interpersonal distance. In the second part of this review, we will discuss the potential influence of self-blaming moral emotions on overt behavior in MDD, reviewing clinical and experimental studies in social and financial decision-making, in which guilt, and shame were manipulated. This is not a well-established area in the depression literature, however in this opinion paper we will argue that studies of moral emotions and their impact on behavioral decision-making are of potential importance in the clinical field, by linking specific symptoms of a disorder to a behavioral outcome which may lead to stratification of clinical diagnoses in the future. PMID:23750148

Deep Learning in Drug Discovery.

Science.gov (United States)

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

2016-01-01

Artificial neural networks had their first heyday in molecular informatics and drug discovery approximately two decades ago. Currently, we are witnessing renewed interest in adapting advanced neural network architectures for pharmaceutical research by borrowing from the field of "deep learning". Compared with some of the other life sciences, their application in drug discovery is still limited. Here, we provide an overview of this emerging field of molecular informatics, present the basic concepts of prominent deep learning methods and offer motivation to explore these techniques for their usefulness in computer-assisted drug discovery and design. We specifically emphasize deep neural networks, restricted Boltzmann machine networks and convolutional networks. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioinformatics in translational drug discovery.

Science.gov (United States)

Wooller, Sarah K; Benstead-Hume, Graeme; Chen, Xiangrong; Ali, Yusuf; Pearl, Frances M G

2017-08-31

Bioinformatics approaches are becoming ever more essential in translational drug discovery both in academia and within the pharmaceutical industry. Computational exploitation of the increasing volumes of data generated during all phases of drug discovery is enabling key challenges of the process to be addressed. Here, we highlight some of the areas in which bioinformatics resources and methods are being developed to support the drug discovery pipeline. These include the creation of large data warehouses, bioinformatics algorithms to analyse 'big data' that identify novel drug targets and/or biomarkers, programs to assess the tractability of targets, and prediction of repositioning opportunities that use licensed drugs to treat additional indications. © 2017 The Author(s).

Discovery of Allostery in PKA Signaling.

Science.gov (United States)

Zhang, Ping; Kornev, Alexandr P; Wu, Jian; Taylor, Susan S

2015-06-01

cAMP-dependent protein kinase (PKA) was the second protein kinase to be discovered and the PKA catalytic (C) subunit serves as a prototype for the large protein kinase superfamily that contains over 500 gene products. The protein kinases regulate much of biology in eukaryotic cells and they are now also a major therapeutic target. Although PKA was discovered nearly 50 years ago and the subsequent discovery of the regulatory subunits that bind cAMP and release the catalytic activity from the holoenzyme followed quickly. Thus in PKA we see the convergence of two major signaling mechanisms - protein phosphorylation and second messenger signaling through cAMP. Crystallography provides a foundation for understanding function, and the structure of the isolated regulatory (R) and C-subunits have been extremely informative. Yet it is the R 2 C 2 holoenzyme that predominates in cells, and one can only appreciate the allosteric features of PKA signaling by seeing the full length protein. The symmetry and the quaternary constraints that one R:C hetero-dimer exerts on the other in the holoenzyme simply are not present in the isolated subunits or even in the R:C hetero-dimer.

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

Directory of Open Access Journals (Sweden)

Nicholas Ekow Thomford

2018-05-01

Full Text Available The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.

Science.gov (United States)

Thomford, Nicholas Ekow; Senthebane, Dimakatso Alice; Rowe, Arielle; Munro, Daniella; Seele, Palesa; Maroyi, Alfred; Dzobo, Kevin

2018-05-25

The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of "active compound" has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of 'organ-on chip' and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review

Discovery and Reuse of Open Datasets: An Exploratory Study

Directory of Open Access Journals (Sweden)

Sara

2016-07-01

Full Text Available Objective: This article analyzes twenty cited or downloaded datasets and the repositories that house them, in order to produce insights that can be used by academic libraries to encourage discovery and reuse of research data in institutional repositories. Methods: Using Thomson Reuters’ Data Citation Index and repository download statistics, we identified twenty cited/downloaded datasets. We documented the characteristics of the cited/downloaded datasets and their corresponding repositories in a self-designed rubric. The rubric includes six major categories: basic information; funding agency and journal information; linking and sharing; factors to encourage reuse; repository characteristics; and data description. Results: Our small-scale study suggests that cited/downloaded datasets generally comply with basic recommendations for facilitating reuse: data are documented well; formatted for use with a variety of software; and shared in established, open access repositories. Three significant factors also appear to contribute to dataset discovery: publishing in discipline-specific repositories; indexing in more than one location on the web; and using persistent identifiers. The cited/downloaded datasets in our analysis came from a few specific disciplines, and tended to be funded by agencies with data publication mandates. Conclusions: The results of this exploratory research provide insights that can inform academic librarians as they work to encourage discovery and reuse of institutional datasets. Our analysis also suggests areas in which academic librarians can target open data advocacy in their communities in order to begin to build open data success stories that will fuel future advocacy efforts.

Arthritis Genetics Analysis Aids Drug Discovery

Science.gov (United States)

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

Solution NMR Spectroscopy in Target-Based Drug Discovery.

Science.gov (United States)

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.

Bioinformatics for cancer immunotherapy target discovery

DEFF Research Database (Denmark)

Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

2014-01-01

therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...

Vaccines Through Centuries: Major Cornerstones of Global Health

Directory of Open Access Journals (Sweden)

Inaya eHajj Hussein

2015-11-01

Full Text Available Multiple cornerstones have shaped the history of vaccines, which may contain live attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response.The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the 18th century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on small pox.The 19th century was a major landmark, with the Germ Theory of disease of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for BCG, Polio, DTP, measles, yellow fever and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010 The Decade of vaccines was launched, and on April 1st 2012, the United Nations launched the shot@Life campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated

Discovery of the Higgs boson

CERN Document Server

Sharma, Vivek

2016-01-01

The recent observation of the Higgs boson has been hailed as the scientific discovery of the century and led to the 2013 Nobel Prize in physics. This book describes the detailed science behind the decades-long search for this elusive particle at the Large Electron Positron Collider at CERN and at the Tevatron at Fermilab and its subsequent discovery and characterization at the Large Hadron Collider at CERN. Written by physicists who played leading roles in this epic search and discovery, this book is an authoritative and pedagogical exposition of the portrait of the Higgs boson that has emerged from a large number of experimental measurements. As the first of its kind, this book should be of interest to graduate students and researchers in particle physics.

Price discovery in European natural gas markets

International Nuclear Information System (INIS)

Schultz, Emma; Swieringa, John

2013-01-01

We provide the first high-frequency investigation of price discovery within the physical and financial layers of Europe's natural gas markets. Testing not only looks at short-term return dynamics, but also considers each security's contribution to price equilibrium in the longer-term. Results show that UK natural gas futures traded on the Intercontinental Exchange display greater price discovery than physical trading at various hubs throughout Europe. - Highlights: • We use intraday data to gauge price discovery in European natural gas markets. • We explore short and long-term dynamics in physical and financial market layers. • Results show ICE's UK natural gas futures are the main venue for price discovery

Intraday Price Discovery in Fragmented Markets

NARCIS (Netherlands)

S.R. Ozturk (Sait); M. van der Wel (Michel); D.J.C. van Dijk (Dick)

2014-01-01

textabstractFor many assets, trading is fragmented across multiple exchanges. Price discovery measures summarize the informativeness of trading on each venue for discovering the asset’s true underlying value. We explore intraday variation in price discovery using a structural model with

Efficient discovery of responses of proteins to compounds using active learning

Science.gov (United States)

2014-01-01

Background Drug discovery and development has been aided by high throughput screening methods that detect compound effects on a single target. However, when using focused initial screening, undesirable secondary effects are often detected late in the development process after significant investment has been made. An alternative approach would be to screen against undesired effects early in the process, but the number of possible secondary targets makes this prohibitively expensive. Results This paper describes methods for making this global approach practical by constructing predictive models for many target responses to many compounds and using them to guide experimentation. We demonstrate for the first time that by jointly modeling targets and compounds using descriptive features and using active machine learning methods, accurate models can be built by doing only a small fraction of possible experiments. The methods were evaluated by computational experiments using a dataset of 177 assays and 20,000 compounds constructed from the PubChem database. Conclusions An average of nearly 60% of all hits in the dataset were found after exploring only 3% of the experimental space which suggests that active learning can be used to enable more complete characterization of compound effects than otherwise affordable. The methods described are also likely to find widespread application outside drug discovery, such as for characterizing the effects of a large number of compounds or inhibitory RNAs on a large number of cell or tissue phenotypes. PMID:24884564

Knowledge Discovery in Data in Construction Projects

Directory of Open Access Journals (Sweden)

Szelka J.

2016-06-01

Full Text Available Decision-making processes, including the ones related to ill-structured problems, are of considerable significance in the area of construction projects. Computer-aided inference under such conditions requires the employment of specific methods and tools (non-algorithmic ones, the best recognized and successfully used in practice represented by expert systems. The knowledge indispensable for such systems to perform inference is most frequently acquired directly from experts (through a dialogue: a domain expert - a knowledge engineer and from various source documents. Little is known, however, about the possibility of automating knowledge acquisition in this area and as a result, in practice it is scarcely ever used. It has to be noted that in numerous areas of management more and more attention is paid to the issue of acquiring knowledge from available data. What is known and successfully employed in the practice of aiding the decision-making is the different methods and tools. The paper attempts to select methods for knowledge discovery in data and presents possible ways of representing the acquired knowledge as well as sample tools (including programming ones, allowing for the use of this knowledge in the area under consideration.

Informing child welfare policy and practice: using knowledge discovery and data mining technology via a dynamic Web site.

Science.gov (United States)

Duncan, Dean F; Kum, Hye-Chung; Weigensberg, Elizabeth Caplick; Flair, Kimberly A; Stewart, C Joy

2008-11-01

Proper management and implementation of an effective child welfare agency requires the constant use of information about the experiences and outcomes of children involved in the system, emphasizing the need for comprehensive, timely, and accurate data. In the past 20 years, there have been many advances in technology that can maximize the potential of administrative data to promote better evaluation and management in the field of child welfare. Specifically, this article discusses the use of knowledge discovery and data mining (KDD), which makes it possible to create longitudinal data files from administrative data sources, extract valuable knowledge, and make the information available via a user-friendly public Web site. This article demonstrates a successful project in North Carolina where knowledge discovery and data mining technology was used to develop a comprehensive set of child welfare outcomes available through a public Web site to facilitate information sharing of child welfare data to improve policy and practice.

User needs analysis and usability assessment of DataMed - a biomedical data discovery index.

Science.gov (United States)

Dixit, Ram; Rogith, Deevakar; Narayana, Vidya; Salimi, Mandana; Gururaj, Anupama; Ohno-Machado, Lucila; Xu, Hua; Johnson, Todd R

2017-11-30

To present user needs and usability evaluations of DataMed, a Data Discovery Index (DDI) that allows searching for biomedical data from multiple sources. We conducted 2 phases of user studies. Phase 1 was a user needs analysis conducted before the development of DataMed, consisting of interviews with researchers. Phase 2 involved iterative usability evaluations of DataMed prototypes. We analyzed data qualitatively to document researchers' information and user interface needs. Biomedical researchers' information needs in data discovery are complex, multidimensional, and shaped by their context, domain knowledge, and technical experience. User needs analyses validate the need for a DDI, while usability evaluations of DataMed show that even though aggregating metadata into a common search engine and applying traditional information retrieval tools are promising first steps, there remain challenges for DataMed due to incomplete metadata and the complexity of data discovery. Biomedical data poses distinct problems for search when compared to websites or publications. Making data available is not enough to facilitate biomedical data discovery: new retrieval techniques and user interfaces are necessary for dataset exploration. Consistent, complete, and high-quality metadata are vital to enable this process. While available data and researchers' information needs are complex and heterogeneous, a successful DDI must meet those needs and fit into the processes of biomedical researchers. Research directions include formalizing researchers' information needs, standardizing overviews of data to facilitate relevance judgments, implementing user interfaces for concept-based searching, and developing evaluation methods for open-ended discovery systems such as DDIs. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A Taxonomy of Self-configuring Service Discovery Systems

NARCIS (Netherlands)

Sundramoorthy, V.; Hartel, Pieter H.; Scholten, Johan

2007-01-01

We analyze the fundamental concepts and issues in service discovery. This analysis places service discovery in the context of distributed systems by describing service discovery as a third generation naming system. We also describe the essential architectures and the functionalities in service

Discovery stories in the science classroom

Science.gov (United States)

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

Applied metabolomics in drug discovery.

Science.gov (United States)

Cuperlovic-Culf, M; Culf, A S

2016-08-01

The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs. This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads.

Discover collaboration: Collaborative learning from the implementation of a discovery system

Directory of Open Access Journals (Sweden)

Åsa Forsberg

2013-12-01

Full Text Available Background Lund University Library purchased and implemented a new discovery system in the end of 2011 and the beginning of 2012. Historically there has been no collaboration between the digital library unit and the pedagogical unit at the University Library. The conditions for the implementation were quite difficult; an extremely tight time frame, changes of the member of staff, high demands from the library network, a bad relation with current system supplier, a dependency of the current system and its functionalities. What to do? In order to reach trustworthiness and to make sure that we have a learning perspective in all the processes we initiated a close collaboration between the digital unit and the pedagogical unit and formed an implementation group. We also initiated a close and active collaboration between the implementation group and an expert group formed by members from the faculty libraries i.e. the super user group. Activities We had four workshops about pedagogical issues regarding discovery systems. The workshops turned out to be a forum for a dialogue between the digital library, the pedagogical unit and the teacher librarians. They resulted in an action plan which was integrated in the implementation process. We also invited colleagues to informal discussions about the pedagogical use of the discovery system. We encouraged all teaching librarians to share their educational materials on our intranet. Conclusion We found the collaborative strategy fruitful and not only did it result in a closer collaboration between the digital library and the pedagogical unit but also with the library network. Due to several reasons we conducted a new tender of a discovery system during 2012. The tender resulted in a new system with a different supplier. In the implementation started in the autumn 2012, we implemented the experiences and learnings gained by our previous implementation.

NMR approaches in structure-based lead discovery: recent developments and new frontiers for targeting multi-protein complexes.

Science.gov (United States)

Dias, David M; Ciulli, Alessio

2014-01-01

Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information on protein structure, dynamics and interaction at an atomic level in solution. Nowadays, in most ligand screening cascades, NMR-based methods are applied to identify and structurally validate small molecule binding. These can be high-throughput and are often used synergistically with other biophysical assays. Here, we describe current state-of-the-art in the portfolio of available NMR-based experiments that are used to aid early-stage lead discovery. We then focus on multi-protein complexes as targets and how NMR spectroscopy allows studying of interactions within the high molecular weight assemblies that make up a vast fraction of the yet untargeted proteome. Finally, we give our perspective on how currently available methods could build an improved strategy for drug discovery against such challenging targets. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Predicting future discoveries from current scientific literature.

Science.gov (United States)

Petrič, Ingrid; Cestnik, Bojan

2014-01-01

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

Business intelligence making decisions through data analytics

CERN Document Server

Surma, Jerzy

2014-01-01

This book is about using business intelligence as a management information system for supporting managerial decision making. It concentrates primarily on practical business issues and demonstrates how to apply data warehousing and data analytics to support business decision making. This book progresses through a logical sequence, starting with data model infrastructure, then data preparation, followed by data analysis, integration, knowledge discovery, and finally the actual use of discovered knowledge. All examples are based on the most recent achievements in business intelligence. Finally this book outlines an overview of a methodology that takes into account the complexity of developing applications in an integrated business intelligence environment. This book is written for managers, business consultants, and undergraduate and postgraduates students in business administration.

Marine viruses--major players in the global ecosystem.

Science.gov (United States)

Suttle, Curtis A

2007-10-01

Viruses are by far the most abundant 'lifeforms' in the oceans and are the reservoir of most of the genetic diversity in the sea. The estimated 10(30) viruses in the ocean, if stretched end to end, would span farther than the nearest 60 galaxies. Every second, approximately 10(23) viral infections occur in the ocean. These infections are a major source of mortality, and cause disease in a range of organisms, from shrimp to whales. As a result, viruses influence the composition of marine communities and are a major force behind biogeochemical cycles. Each infection has the potential to introduce new genetic information into an organism or progeny virus, thereby driving the evolution of both host and viral assemblages. Probing this vast reservoir of genetic and biological diversity continues to yield exciting discoveries.

GeoSearch: A lightweight broking middleware for geospatial resources discovery

Science.gov (United States)

Gui, Z.; Yang, C.; Liu, K.; Xia, J.

2012-12-01

With petabytes of geodata, thousands of geospatial web services available over the Internet, it is critical to support geoscience research and applications by finding the best-fit geospatial resources from the massive and heterogeneous resources. Past decades' developments witnessed the operation of many service components to facilitate geospatial resource management and discovery. However, efficient and accurate geospatial resource discovery is still a big challenge due to the following reasons: 1)The entry barriers (also called "learning curves") hinder the usability of discovery services to end users. Different portals and catalogues always adopt various access protocols, metadata formats and GUI styles to organize, present and publish metadata. It is hard for end users to learn all these technical details and differences. 2)The cost for federating heterogeneous services is high. To provide sufficient resources and facilitate data discovery, many registries adopt periodic harvesting mechanism to retrieve metadata from other federated catalogues. These time-consuming processes lead to network and storage burdens, data redundancy, and also the overhead of maintaining data consistency. 3)The heterogeneous semantics issues in data discovery. Since the keyword matching is still the primary search method in many operational discovery services, the search accuracy (precision and recall) is hard to guarantee. Semantic technologies (such as semantic reasoning and similarity evaluation) offer a solution to solve these issues. However, integrating semantic technologies with existing service is challenging due to the expandability limitations on the service frameworks and metadata templates. 4)The capabilities to help users make final selection are inadequate. Most of the existing search portals lack intuitive and diverse information visualization methods and functions (sort, filter) to present, explore and analyze search results. Furthermore, the presentation of the value

The neutron discovery

International Nuclear Information System (INIS)

Six, J.

1987-01-01

The neutron: who had first the idea, who discovered it, who established its main properties. To these apparently simple questions, multiple answers exist. The progressive discovery of the neutron is a marvellous illustration of some characteristics of the scientific research, where the unforeseen may be combined with the expected. This discovery is replaced in the context of the 1930's scientific effervescence that succeeded the revolutionary introduction of quantum mechanics. This book describes the works of Bothe, the Joliot-Curie and Chadwick which led to the neutron in an unexpected way. A historical analysis allows to give a new interpretation on the hypothesis suggested by the Joliot-Curie. Some texts of these days will help the reader to revive this fascinating story [fr

Viral pathogen discovery

Science.gov (United States)

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

Making the Introductory Meteorology Class Relevant in a Minority Serving Community College

Science.gov (United States)

Marchese, P. J.; Tremberger, G.; Bluestone, C.

2008-12-01

Queensborough Community College (QCC), a constituent campus of the City University of New York (CUNY), has modified the introductory Meteorology Class lecture and lab to include active learning activities and discovery based learning. The modules were developed at QCC and other 4 year colleges and designed to introduce basic physical concepts important in meteorology. The modules consisted of either interactive lecture demonstrations or discovery-based activities. The discovery based activities are intended to have students become familiar with scientific investigation. Students engage in formulating hypotheses, developing and carrying out experiments, and analyzing scientific data. These activities differ from traditional lab experiments in that they avoid "cookbook" procedures and emphasize having the students learn about physical concepts by applying the scientific method. During the interactive lecture demonstrations the instructor describes an experiment/phenomenon that is to be demonstrated in class. Students discuss the phenomenon based on their experiences and make a prediction about the outcome. The class then runs the experiment, makes observations, and compares the expected results to the actual outcome. As a result of these activities students in the introductory Meteorology class scored higher in exams questions measuring conceptual understanding, as well as factual knowledge. Lower scoring students demonstrated the greatest benefit, while the better students had little (or no) changes. All students also had higher self-efficacy scores after the intervention, compared to an unmodified class.

Benefit-risk trade-offs in retrospect: how major stakeholders perceive the decision-making process in the Barents Sea oil field development

DEFF Research Database (Denmark)

Renn, Ortwin; Grieger, Khara Deanne; Øien, Knut

2013-01-01

review of the decision-making process seen through the lenses of the major stakeholders involved in this process. The research design used qualitative methods of empirical research including stakeholder interviews during a five-day period in 2011 in Northern Norway. Results showed that the siting process...... additional benefits to the communities which would then be fairly distributed among the beneficiaries have been disappointed. We review the reasons behind these results as well as formulate recommendations regarding potential improvements to the risk-benefit communication process in addition to future siting...

Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder.

Science.gov (United States)

Yang, Xin-hua; Huang, Jia; Lan, Yong; Zhu, Cui-ying; Liu, Xiao-qun; Wang, Ye-fei; Cheung, Eric F C; Xie, Guang-rong; Chan, Raymond C K

2016-01-04

Anhedonia, the loss of interest or pleasure in reward processing, is a hallmark feature of major depressive disorder (MDD), but its underlying neurobiological mechanism is largely unknown. The present study aimed to examine the underlying neural mechanism of reward-related decision-making in patients with MDD. We examined behavioral and neural responses to rewards in patients with first-episode MDD (N=25) and healthy controls (N=25) using the Effort-Expenditure for Rewards Task (EEfRT). The task involved choices about possible rewards of varying magnitude and probability. We tested the hypothesis that individuals with MDD would exhibit a reduced neural response in reward-related brain structures involved in cost-benefit decision-making. Compared with healthy controls, patients with MDD showed significantly weaker responses in the left caudate nucleus when contrasting the 'high reward'-'low reward' condition, and blunted responses in the left superior temporal gyrus and the right caudate nucleus when contrasting high and low probabilities. In addition, hard tasks chosen during high probability trials were negatively correlated with superior temporal gyrus activity in MDD patients, while the same choices were negatively correlated with caudate nucleus activity in healthy controls. These results indicate that reduced caudate nucleus and superior temporal gyrus activation may underpin abnormal cost-benefit decision-making in MDD. Copyright © 2015 Elsevier Inc. All rights reserved.

Synthetic biology for pharmaceutical drug discovery

Directory of Open Access Journals (Sweden)

Trosset JY

2015-12-01

Full Text Available Jean-Yves Trosset,1 Pablo Carbonell2,3 1Bioinformation Research Laboratory, Sup’Biotech, Villejuif, France; 2Faculty of Life Sciences, SYNBIOCHEM Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK; 3Department of Experimental and Health Sciences (DCEXS, Research Programme on Biomedical Informatics (GRIB, Hospital del Mar Medical Research Institute (IMIM, Universitat Pompeu Fabra (UPF, Barcelona, Spain Abstract: Synthetic biology (SB is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell–cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity. Keywords: metabolic engineering, plant synthetic biology, natural products, synthetic quorum sensing, drug resistance

Biotechnology and Consumer Decision-Making.

Science.gov (United States)

Sax, Joanna K

Society is facing major challenges in climate change, health care and overall quality of life. Scientific advances to address these areas continue to grow, with overwhelming evidence that the application of highly tested forms of biotechnology is safe and effective. Despite scientific consensus in these areas, consumers appear reluctant to support their use. Research that helps to understand consumer decision-making and the public’s resistance to biotechnologies such as vaccines, fluoridated water programs and genetically engineered food, will provide great social value. This article is forward-thinking in that it suggests that important research in behavioral decision-making, specifically affect and ambiguity, can be used to help consumers make informed choices about major applications of biotechnology. This article highlights some of the most controversial examples: vaccinations, genetically engineered food, rbST treated dairy cows, fluoridated water, and embryonic stem cell research. In many of these areas, consumers perceive the risks as high, but the experts calculate the risks as low. Four major thematic approaches are proposed to create a roadmap for policymakers to consider for policy design and implementation in controversial areas of biotechnology. This article articulates future directions for studies that implement decision-making research to allow consumers to appropriately assign risk to their options and make informed decisions.

Discovery and Characterization of a Higgs boson using four-lepton events from the CMS

Energy Technology Data Exchange (ETDEWEB)

Martin, Christopher Blake [Johns Hopkins Univ., Baltimore, MD (United States)

2015-07-01

A new particle decaying to a pair of vector bosons was discovered in 2012 by the ATLAS and CMS experiments at the Large Hadron Collider. In the wake of this discovery a rush of measurements was made to characterize this particle. The fourlepton final state has been instrumental in both the discovery and characterization of this new particle. With only about 20 events seen in the resonance peak at 125 GeV the CMS experiment has been able to make considerable progress in characterizing the Higgs-like boson using the wealth of information in this final state in concert with other decay modes. In addition to the search for this new boson we present three recent results in the study of the Higgs-like boson properties: studies of the production mode, total width, and spin-parity quantum numbers.

Lise Meitner and fission: Fallout from the discovery

International Nuclear Information System (INIS)

Sime, R.L.

1991-01-01

Much has been written about Lise Meitner, but she remains on the periphery. Of her pioneering work in nuclear physics, little is said; she is remembered primarily for nuclear fission, a discovery in which she did not share. Especially in Germany the staging seldom varies: Otto Hahn in the spotlight, Fritz Strassmann in his shadow, Lise Meitner in the wings, dimly outlined in reflected light. Her role is open to speculation. One writer sees her work 'crowned by the Nobel Prize for Otto Hahn', another, once director of an institute that bears her name, portrays her as the physicist who obstructed the discovery from the start. Often she is cast as Hahn's Mitarbeiterin; sometimes she is completely invisible, as in one of the world's great science museums, which for 30 years displayed the fission apparatus-equipment assembled by Lise Meitner on a table in her laboratory in her physics section of the Kaiser-Wilhelm-Institut fuer Chemie - without ever mentioning her name. The principals themselves do not agree. In his memoirs, Hahn has remarkably little to say of this closest colleague and friend. From Lise Meitner herself we have no autobiography. Available, however, is the large collection of letters and documents she has left behind, and these make it possible for us to learn much more. (orig./BBR)

Lise Meitner and fission: Fallout from the discovery

Energy Technology Data Exchange (ETDEWEB)

Sime, R.L. (Sacramento City Coll., CA (United States). Dept. of Chemistry)

1991-08-01

Much has been written about Lise Meitner, but she remains on the periphery. Of her pioneering work in nuclear physics, little is said; she is remembered primarily for nuclear fission, a discovery in which she did not share. Especially in Germany the staging seldom varies: Otto Hahn in the spotlight, Fritz Strassmann in his shadow, Lise Meitner in the wings, dimly outlined in reflected light. Her role is open to speculation. One writer sees her work 'crowned by the Nobel Prize for Otto Hahn', another, once director of an institute that bears her name, portrays her as the physicist who obstructed the discovery from the start. Often she is cast as Hahn's Mitarbeiterin; sometimes she is completely invisible, as in one of the world's great science museums, which for 30 years displayed the fission apparatus-equipment assembled by Lise Meitner on a table in her laboratory in her physics section of the Kaiser-Wilhelm-Institut fuer Chemie - without ever mentioning her name. The principals themselves do not agree. In his memoirs, Hahn has remarkably little to say of this closest colleague and friend. From Lise Meitner herself we have no autobiography. Available, however, is the large collection of letters and documents she has left behind, and these make it possible for us to learn much more. (orig./BBR).

Seeking Ligand Bias: Assessing GPCR Coupling to Beta-Arrestins for Drug Discovery

OpenAIRE

Bohn, Laura M.; McDonald, Patricia H.

2010-01-01

G protein-coupled receptors (GPCR) are the major site of action for endogenous hormones and neurotransmitters. Early drug discovery efforts focused on determining whether ligands could engage G protein coupling and subsequently activate or inhibit cognate “second messengers.” Gone are those simple days as we now realize that receptors can also couple βarrestins. As we delve into the complexity of ligand-directed signaling and receptosome scaffolds, we are faced with what may seem like endless...

Digital One Disc One Compound Method for High Throughput Discovery of Prostate Cancer Targeting Ligands

Science.gov (United States)

2016-12-01

efficiency of drug discovery and make a potential impact on modern pharmaceutical industries . 15. SUBJECT TERMS ODOC carriers, barcode, split-mix...approach4-7. Array technologies can construct high density of molecules in an array format on a solid substrate (microchip), from which the chemical...and-play microfluidic packaging scheme, known as Microflego – 3D Microfluidic Assembly, to facilely establish complex 3D microfluidic networks using

Public-Private Partnerships in Lead Discovery: Overview and Case Studies.

Science.gov (United States)

Gottwald, Matthias; Becker, Andreas; Bahr, Inke; Mueller-Fahrnow, Anke

2016-09-01

The pharmaceutical industry is faced with significant challenges in its efforts to discover new drugs that address unmet medical needs. Safety concerns and lack of efficacy are the two main technical reasons for attrition. Improved early research tools including predictive in silico, in vitro, and in vivo models, as well as a deeper understanding of the disease biology, therefore have the potential to improve success rates. The combination of internal activities with external collaborations in line with the interests and needs of all partners is a successful approach to foster innovation and to meet the challenges. Collaboration can take place in different ways, depending on the requirements of the participants. In this review, the value of public-private partnership approaches will be discussed, using examples from the Innovative Medicines Initiative (IMI). These examples describe consortia approaches to develop tools and processes for improving target identification and validation, as well as lead identification and optimization. The project "Kinetics for Drug Discovery" (K4DD), focusing on the adoption of drug-target binding kinetics analysis in the drug discovery decision-making process, is described in more detail. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

"Metabolic staging" after major trauma - a guide for clinical decision making?

Directory of Open Access Journals (Sweden)

Moore Ernest E

2010-06-01

Full Text Available Abstract Metabolic changes after major trauma have a complex underlying pathophysiology. The early posttraumatic stress response is associated with a state of hyperinflammation, with increased oxygen consumption and energy expenditure. This hypercatabolic state must be recognized early and mandates an early nutritional management strategy. A proactive concept of early enteral "immunonutrition" in severely injured patients, is aimed at counterbalancing the negative aspects of hyperinflammation and hypercatabolism in order to reduce the risk of late complications, including infections and posttraumatic organ failure. Recently, the concept of "metabolic staging" has been advocated, which takes into account the distinct inflammatory phases and metabolic phenotypes after major trauma, including the "ischemia/reperfusion phenotype", the "leukocytic phenotype", and the "angiogenic phenotype". The potential clinical impact of metabolic staging, and of an appropriately adapted "metabolic control" and nutritional support, remains to be determined.

Predictors of timing of pregnancy discovery.

Science.gov (United States)

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.

Book Review: Dispute Resolution and e-Discovery

Directory of Open Access Journals (Sweden)

Milton Luoma

2012-09-01

Full Text Available Garrie, D.B., & Griver, Y.M., Eds. (2012. Dispute Resolution and e-Discovery. Thomson Reuters Westlaw, 570 pages, ISBN-13: 9780314604484, US$149.00.Reviewed by Milton Luoma, JD, (Milt.Luoma@metrostate.eduAs is apparent from its title, this book tackles two very current and difficult legal issues – electronic discovery and dispute resolution. The authors tie the two legal concepts together in an effort to provide litigants and practitioners a less expensive and less time consuming alternative than is typically the case with traditional litigation and court proceedings. By including electronic discovery in the discussions, the authors recognize the importance and significance of electronic discovery in mediation and arbitration as it is in traditional litigation.(see PDF for full review

BayesMotif: de novo protein sorting motif discovery from impure datasets.

Science.gov (United States)

Hu, Jianjun; Zhang, Fan

2010-01-18

Protein sorting is the process that newly synthesized proteins are transported to their target locations within or outside of the cell. This process is precisely regulated by protein sorting signals in different forms. A major category of sorting signals are amino acid sub-sequences usually located at the N-terminals or C-terminals of protein sequences. Genome-wide experimental identification of protein sorting signals is extremely time-consuming and costly. Effective computational algorithms for de novo discovery of protein sorting signals is needed to improve the understanding of protein sorting mechanisms. We formulated the protein sorting motif discovery problem as a classification problem and proposed a Bayesian classifier based algorithm (BayesMotif) for de novo identification of a common type of protein sorting motifs in which a highly conserved anchor is present along with a less conserved motif regions. A false positive removal procedure is developed to iteratively remove sequences that are unlikely to contain true motifs so that the algorithm can identify motifs from impure input sequences. Experiments on both implanted motif datasets and real-world datasets showed that the enhanced BayesMotif algorithm can identify anchored sorting motifs from pure or impure protein sequence dataset. It also shows that the false positive removal procedure can help to identify true motifs even when there is only 20% of the input sequences containing true motif instances. We proposed BayesMotif, a novel Bayesian classification based algorithm for de novo discovery of a special category of anchored protein sorting motifs from impure datasets. Compared to conventional motif discovery algorithms such as MEME, our algorithm can find less-conserved motifs with short highly conserved anchors. Our algorithm also has the advantage of easy incorporation of additional meta-sequence features such as hydrophobicity or charge of the motifs which may help to overcome the limitations of

Pharmaceutical structure montages as catalysts for design and discovery.

Science.gov (United States)

Njarðarson, Jon T

2012-05-01

Majority of pharmaceuticals are small molecule organic compounds. Their structures are most effectively described and communicated using the graphical language of organic chemistry. A few years ago we decided to harness this powerful language to create new educational tools that could serve well for data mining and as catalysts for discovery. The results were the Top 200 drug posters, which we have posted online for everyone to enjoy and update yearly. This article details the origin and motivation for our design and highlights the value of this graphical format by presenting and analyzing a new pharmaceutical structure montage (poster) focused on US FDA approved drugs in 2011.

The Development of Critical Thinking Skills for Elementary Education Majors at Castleton State College.

Science.gov (United States)

Forest, Robert F.

The document describes a practicum which developed a unit on critical thinking that applied Jerome Bruner's discovery-learning method and also incorporated the unit within the curricular requirements of elementary education majors at Castleton State College in Vermont. It is presented in five sections and an appendix. Section I provides…

Testing jumps via false discovery rate control.

Science.gov (United States)

Yen, Yu-Min

2013-01-01

Many recently developed nonparametric jump tests can be viewed as multiple hypothesis testing problems. For such multiple hypothesis tests, it is well known that controlling type I error often makes a large proportion of erroneous rejections, and such situation becomes even worse when the jump occurrence is a rare event. To obtain more reliable results, we aim to control the false discovery rate (FDR), an efficient compound error measure for erroneous rejections in multiple testing problems. We perform the test via the Barndorff-Nielsen and Shephard (BNS) test statistic, and control the FDR with the Benjamini and Hochberg (BH) procedure. We provide asymptotic results for the FDR control. From simulations, we examine relevant theoretical results and demonstrate the advantages of controlling the FDR. The hybrid approach is then applied to empirical analysis on two benchmark stock indices with high frequency data.

The Discovery of Arthropod-Specific Viruses in Hematophagous Arthropods: An Open Door to Understanding the Mechanisms of Arbovirus and Arthropod Evolution?

Science.gov (United States)

Calisher, Charles H; Higgs, Stephen

2018-01-07

The discovery of an odd virus from hematophagous arthropods 40 years ago by Stollar and Thomas described cell fusing agent virus in cells derived from Aedes aegypti mosquitoes. Then came the report of Kamiti River virus from Ae. macintoshi in 1999, followed by worldwide reports of the discovery of other viruses of mosquitoes, ticks, and midges that replicate only in arthropods and not in vertebrates or in vertebrate cells. These viruses (now totaling at least 64 published) have genomes analogous to viruses in various families that include arboviruses and nonarboviruses. It is likely that some of these viruses have been insufficiently studied and may yet be shown to infect vertebrates. However, there is no doubt that the vast majority are restricted to arthropods alone and that they represent a recently recognized clade. Their biology, modes of transmission, worldwide distribution (some have been detected in wild-caught mosquitoes in both Asia and the United States, for example), molecular characteristics of their genomes, and potential for becoming vertebrate pathogens, or at least serving as virus reservoirs, are fascinating and may provide evidence useful in understanding virus evolution. Because metagenomics studies of arthropods have shown that arthropod genomes are the sources of arthropod virus genomes, further studies may also provide insights into the evolution of arthropods. More recently, others have published excellent papers that briefly review discoveries of arthropod viruses and that characterize certain genomic peculiarities, but, to now, there have been no reviews that encompass all these facets. We therefore anticipate that this review is published at a time and in a manner that is helpful for both virologists and entomologists to make more sense and understanding of this recently recognized and obviously important virus group. This review focuses specifically on arthropod viruses in hematophagous arthropods.

Managing discovery risks--A Tevatron case study

International Nuclear Information System (INIS)

Bakul Banerjee

2004-01-01

To meet the increasing need for higher performance, Management of Fermi National Accelerator Laboratory has undertaken various projects to improve systems associated with the Tevatron high-energy particle collider located at Batavia, Illinois. One of the larger projects is the Tevatron Beam Position Monitor (BPM) system. The objective of this project is to replace the existing BPM electronics and software system that was originally installed during early 1980s, along with the original construction of the Tevatron.The original system consists of 236 beam position monitors located around the underground tunnel of the accelerator. Above ground control systems are attached to these monitors using pickup cables. When the Tevatron collider is operational, signals received from the BPMs are used to perform a number of control and diagnostic tasks. The original system can only capture the proton signals from the collider. The new system, when fully operational, will be able to capture combined proton and antiproton signals and will be able to separate the antiproton signal from the combined signal at high resolution. This significant enhancement was beyond the range of technical capabilities when the Tevatron was constructed about two decades ago. To take advantage of exceptional progress made in the hardware and software area in past two decades, Department of Energy approved funding of the BPM electronics and software replacement project. The approximate length of the project is sixteen months with a budget of four million dollars not including overhead, escalation, and contingencies. Apart from cost and schedule risks, there are two major risks associated with this research and development project. The primary risk is the risk of discovery. Since the Tevatron beam path is highly complex, BPMs have to acquire and process a large amount of data. In this environment, analysis of data to separate antiproton signals is even more complex. Finding an optimum algorithm that can

40 CFR 209.22 - Other discovery.

Science.gov (United States)

2010-07-01

... PRACTICE GOVERNING PROCEEDINGS UNDER THE NOISE CONTROL ACT OF 1972 Rules of Practice Governing Hearings for Orders Issued Under Section 11(d) of the Noise Control Act § 209.22 Other discovery. (a) Further... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Other discovery. 209.22 Section 209.22...

How does non-formal marine education affect student attitude and knowledge? A case study using SCDNR's Discovery program

Science.gov (United States)

McGovern, Mary Francis

Non-formal environmental education provides students the opportunity to learn in ways that would not be possible in a traditional classroom setting. Outdoor learning allows students to make connections to their environment and helps to foster an appreciation for nature. This type of education can be interdisciplinary---students not only develop skills in science, but also in mathematics, social studies, technology, and critical thinking. This case study focuses on a non-formal marine education program, the South Carolina Department of Natural Resources' (SCDNR) Discovery vessel based program. The Discovery curriculum was evaluated to determine impact on student knowledge about and attitude toward the estuary. Students from two South Carolina coastal counties who attended the boat program during fall 2014 were asked to complete a brief survey before, immediately after, and two weeks following the program. The results of this study indicate that both student knowledge about and attitude significantly improved after completion of the Discovery vessel based program. Knowledge and attitude scores demonstrated a positive correlation.

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

Science.gov (United States)

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.

Scientific Knowledge Discovery in Complex Semantic Networks of Geophysical Systems

Science.gov (United States)

Fox, P.

2012-04-01

The vast majority of explorations of the Earth's systems are limited in their ability to effectively explore the most important (often most difficult) problems because they are forced to interconnect at the data-element, or syntactic, level rather than at a higher scientific, or semantic, level. Recent successes in the application of complex network theory and algorithms to climate data, raise expectations that more general graph-based approaches offer the opportunity for new discoveries. In the past ~ 5 years in the natural sciences there has substantial progress in providing both specialists and non-specialists the ability to describe in machine readable form, geophysical quantities and relations among them in meaningful and natural ways, effectively breaking the prior syntax barrier. The corresponding open-world semantics and reasoning provide higher-level interconnections. That is, semantics provided around the data structures, using semantically-equipped tools, and semantically aware interfaces between science application components allowing for discovery at the knowledge level. More recently, formal semantic approaches to continuous and aggregate physical processes are beginning to show promise and are soon likely to be ready to apply to geoscientific systems. To illustrate these opportunities, this presentation presents two application examples featuring domain vocabulary (ontology) and property relations (named and typed edges in the graphs). First, a climate knowledge discovery pilot encoding and exploration of CMIP5 catalog information with the eventual goal to encode and explore CMIP5 data. Second, a multi-stakeholder knowledge network for integrated assessments in marine ecosystems, where the data is highly inter-disciplinary.

Arrayed antibody library technology for therapeutic biologic discovery.

Science.gov (United States)

Bentley, Cornelia A; Bazirgan, Omar A; Graziano, James J; Holmes, Evan M; Smider, Vaughn V

2013-03-15

Traditional immunization and display antibody discovery methods rely on competitive selection amongst a pool of antibodies to identify a lead. While this approach has led to many successful therapeutic antibodies, targets have been limited to proteins which are easily purified. In addition, selection driven discovery has produced a narrow range of antibody functionalities focused on high affinity antagonism. We review the current progress in developing arrayed protein libraries for screening-based, rather than selection-based, discovery. These single molecule per microtiter well libraries have been screened in multiplex formats against both purified antigens and directly against targets expressed on the cell surface. This facilitates the discovery of antibodies against therapeutically interesting targets (GPCRs, ion channels, and other multispanning membrane proteins) and epitopes that have been considered poorly accessible to conventional discovery methods. Copyright © 2013. Published by Elsevier Inc.

CUAHSI Data Services: Tools and Cyberinfrastructure for Water Data Discovery, Research and Collaboration

Science.gov (United States)

Seul, M.; Brazil, L.; Castronova, A. M.

2017-12-01

CUAHSI Data Services: Tools and Cyberinfrastructure for Water Data Discovery, Research and CollaborationEnabling research surrounding interdisciplinary topics often requires a combination of finding, managing, and analyzing large data sets and models from multiple sources. This challenge has led the National Science Foundation to make strategic investments in developing community data tools and cyberinfrastructure that focus on water data, as it is central need for many of these research topics. CUAHSI (The Consortium of Universities for the Advancement of Hydrologic Science, Inc.) is a non-profit organization funded by the National Science Foundation to aid students, researchers, and educators in using and managing data and models to support research and education in the water sciences. This presentation will focus on open-source CUAHSI-supported tools that enable enhanced data discovery online using advanced searching capabilities and computational analysis run in virtual environments pre-designed for educators and scientists so they can focus their efforts on data analysis rather than IT set-up.

Year of the Solar System: New Worlds, New Discoveries and Why People Should Care (Invited)

Science.gov (United States)

Green, J. L.; Adams, J.; McCuistion, D.; Erickson, K. J.

2010-12-01

The next two years represents a historic time in planetary science. In order to better communicate this period to our target audiences, NASA’s Planetary Science Division created the Year of the Solar System (YSS) initiative. YSS is being designed to raise awareness, build excitement and make connections with educators, students and the American public about planetary science events and discoveries. Over the next Martian year, with our international partners we will encounter two comets; orbit spacecraft around Venus, Mercury and Vesta; continue to explore Mars with rovers; and launch robotic explorers to Jupiter, Earth’s moon, and Mars. For the first time ever NASA will launch three planetary missions within four months of each other! With the successful accomplishment of these mission events will come a series of fabulous scientific discoveries. We must take advantage of this unique opportunity to get the word out about the scientific revolution occurring in planetary science. This presentation will also discuss the importance of providing relatable material through Earth analogs, comparative visuals, interactive web-based tools and other ideas to communicate, why people should care about these exciting discoveries to come.

Radioactivity. Centenary of radioactivity discovery

International Nuclear Information System (INIS)

Charpak, G.; Tubiana, M.; Bimbot, R.

1997-01-01

This small booklet was edited for the occasion of the exhibitions of the celebration of the centenary of radioactivity discovery which took place in various locations in France from 1996 to 1998. It recalls some basic knowledge concerning radioactivity and its applications: history of discovery, atoms and isotopes, radiations, measurement of ionizing radiations, natural and artificial radioactivity, isotope dating and labelling, radiotherapy, nuclear power and reactors, fission and fusion, nuclear wastes, dosimetry, effects and radioprotection. (J.S.)

Does Economic Education Make a Difference in Congress? How Economics Majors Vote on Trade

Science.gov (United States)

O'Roark, J. Brian

2012-01-01

The author of this article expands the background theory of voting to incorporate the undergraduate majors of members of Congress. Examining nine votes on trade across the 109th and 110th Congresses reveals that economics majors are the only category of college major to vote in favor of free trade in a predictable way. Controls for a variety of…

Stem cells: a model for screening, discovery and development of drugs

Directory of Open Access Journals (Sweden)

Kitambi SS

2011-09-01

Full Text Available Satish Srinivas Kitambi1, Gayathri Chandrasekar21Department of Medical Biochemistry and Biophysics; 2Department of Biosciences, Karolinska Institutet, Stockholm, SwedenAbstract: The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficacy studies using stem cells offers a reliable platform for the drug discovery process. Advances made in the generation of induced pluripotent stem cells from normal or diseased tissue serves as a platform to perform drug screens aimed at developing cell-based therapies against conditions like Parkinson's disease and diabetes. This review discusses the application of stem cells and cancer stem cells in drug screening and their role in complementing, reducing, and replacing animal testing. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells are also discussed.Keywords: therapeutics, stem cells, cancer stem cells, screening models, drug development, high throughput screening

β-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies.

Science.gov (United States)

Rivella, Stefano

2015-04-01

β-thalassemias are monogenic disorders characterized by defective synthesis of the β-globin chain, one of the major components of adult hemoglobin. A large number of mutations in the β-globin gene or its regulatory elements have been associated with β-thalassemias. Due to the complexity of the regulation of the β-globin gene and the role of red cells in many physiological processes, patients can manifest a large spectrum of phenotypes, and clinical requirements vary from patient to patient. It is important to consider the major differences in the light of potential novel therapeutics. This review summarizes the main discoveries and mechanisms associated with the synthesis of β-globin and abnormal erythropoiesis, as well as current and novel therapies. Copyright© Ferrata Storti Foundation.

Do different fairness contexts and facial emotions motivate 'irrational' social decision-making in major depression? An exploratory patient study.

Science.gov (United States)

Radke, Sina; Schäfer, Ina C; Müller, Bernhard W; de Bruijn, Ellen R A

2013-12-15

Although 'irrational' decision-making has been linked to depression, the contribution of biases in information processing to these findings remains unknown. To investigate the impact of cognitive biases and aberrant processing of facial emotions on social decision-making, we manipulated both context-related and emotion-related information in a modified Ultimatum Game. Unfair offers were (1) paired with different unselected alternatives, establishing the context in which an offer was made, and (2) accompanied by emotional facial expressions of proposers. Responder behavior was assessed in patients with major depressive disorder and healthy controls. In both groups alike, rejection rates were highest following unambiguous signals of unfairness, i.e. an angry proposer face or when an unfair distribution had deliberately been chosen over an equal split. However, depressed patients showed overall higher rejection rates than healthy volunteers, without exhibiting differential processing biases. This suggests that depressed patients were, as healthy individuals, basing their decisions on informative, salient features and differentiating between (i) fair and unfair offers, (ii) alternatives to unfair offers and (iii) proposers' facial emotions. Although more fundamental processes, e.g. reduced reward sensitivity, might underlie increased rejection in depression, the current study provides insight into mechanisms that shape fairness considerations in both depressed and healthy individuals. © 2013 Elsevier Ireland Ltd. All rights reserved.

Emerging Concepts and Methodologies in Cancer Biomarker Discovery.

Science.gov (United States)

Lu, Meixia; Zhang, Jinxiang; Zhang, Lanjing

2017-01-01

Cancer biomarker discovery is a critical part of cancer prevention and treatment. Despite the decades of effort, only a small number of cancer biomarkers have been identified for and validated in clinical settings. Conceptual and methodological breakthroughs may help accelerate the discovery of additional cancer biomarkers, particularly their use for diagnostics. In this review, we have attempted to review the emerging concepts in cancer biomarker discovery, including real-world evidence, open access data, and data paucity in rare or uncommon cancers. We have also summarized the recent methodological progress in cancer biomarker discovery, such as high-throughput sequencing, liquid biopsy, big data, artificial intelligence (AI), and deep learning and neural networks. Much attention has been given to the methodological details and comparison of the methodologies. Notably, these concepts and methodologies interact with each other and will likely lead to synergistic effects when carefully combined. Newer, more innovative concepts and methodologies are emerging as the current emerging ones became mainstream and widely applied to the field. Some future challenges are also discussed. This review contributes to the development of future theoretical frameworks and technologies in cancer biomarker discovery and will contribute to the discovery of more useful cancer biomarkers.

120 YEARS SINCE THE DISCOVERY OF X-RAYS.

Science.gov (United States)

Babic, Rade R; Stankovic Babic, Gordana; Babic, Strahinja R; Babic, Nevena R

2016-09-01

This paper is intended to celebrate the 120th anniversary of the discovery of X-rays. X-rays (Roentgen-rays) were discovered on the 8th ofNovember, 1895 by the German physicist Wilhelm Conrad Roentgen. Fifty days after the discovery of X-ray, on December 28, 1895. Wilhelm Conrad Roentgen published a paper about the discovery of X-rays - "On a new kind of rays" (Wilhelm Conrad Roentgen: Ober eine neue Art von Strahlen. In: Sitzungsberichte der Wurzburger Physik.-Medic.- Gesellschaft. 1895.). Therefore, the date of 28th ofDecember, 1895 was taken as the date of X-rays discovery. This paper describes the work of Wilhelm Conrad Roentgen, Nikola Tesla, Mihajlo Pupin and Maria Sklodowska-Curie about the nature of X-rays . The fantastic four - Wilhelm Conrad Roentgen, NikolaTesla, Mihajlo ldvorski Pupin and Maria Sklodowska-Curie set the foundation of radiology with their discovery and study of X-rays. Five years after the discovery of X-rays, in 1900, Dr Avram Vinaver had the first X-ray machine installed in abac, in Serbia at the time when many developed countries did not have an X-ray machine and thus set the foundation of radiology in Serbia.

"Discoveries in Planetary Sciences": Slide Sets Highlighting New Advances for Astronomy Educators

Science.gov (United States)

Brain, D. A.; Schneider, N. M.; Beyer, R. A.

2010-12-01

Planetary science is a field that evolves rapidly, motivated by spacecraft mission results. Exciting new mission results are generally communicated rather quickly to the public in the form of press releases and news stories, but it can take several years for new advances to work their way into college textbooks. Yet it is important for students to have exposure to these new advances for a number of reasons. In some cases, new work renders older textbook knowledge incorrect or incomplete. In some cases, new discoveries make it possible to emphasize older textbook knowledge in a new way. In all cases, new advances provide exciting and accessible examples of the scientific process in action. To bridge the gap between textbooks and new advances in planetary sciences we have developed content on new discoveries for use by undergraduate instructors. Called 'Discoveries in Planetary Sciences', each new discovery is summarized in a 3-slide PowerPoint presentation. The first slide describes the discovery, the second slide discusses the underlying planetary science concepts, and the third presents the big picture implications of the discovery. A fourth slide includes links to associated press releases, images, and primary sources. This effort is generously sponsored by the Division for Planetary Sciences of the American Astronomical Society, and the slide sets are available at http://dps.aas.org/education/dpsdisc/. Sixteen slide sets have been released so far covering topics spanning all sub-disciplines of planetary science. Results from the following spacecraft missions have been highlighted: MESSENGER, the Spirit and Opportunity rovers, Cassini, LCROSS, EPOXI, Chandrayan, Mars Reconnaissance Orbiter, Mars Express, and Venus Express. Additionally, new results from Earth-orbiting and ground-based observing platforms and programs such as Hubble, Keck, IRTF, the Catalina Sky Survey, HARPS, MEarth, Spitzer, and amateur astronomers have been highlighted. 4-5 new slide sets are

Into the millennium: farewell to majors

International Nuclear Information System (INIS)

Polczer, S.

1999-01-01

Conventional oil discoveries in Alberta peaked in the mid-1960s, marking a shift in the exploration strategies of the oil company majors that established Canada as a player in the world petroleum scene. Increasingly, they are shifting capital out of the country or look to unconventional sources for their new finds. Since they cannot find reserves needed to replace production, major oil companies have began to wind down their exploration programs, or shift to gas or oil sands, or exit altogether. According to the best expert opinion, future traditional exploration and production in Canada will be dominated by technically focused, entrepreneurial niche players using the latest technology to exploit lower quality reservoirs. The same expert source believes that Canada's contribution to the world's petroleum industry after 2000 will be primarily technological development, such as better drilling and well completion techniques. Past evidence suggest that Canada, while not a big player on the world petroleum scene, can and will continue to provide useful contribution to the industry by developing and exporting useful technology

On reliable discovery of molecular signatures

Directory of Open Access Journals (Sweden)

Björkegren Johan

2009-01-01

Full Text Available Abstract Background Molecular signatures are sets of genes, proteins, genetic variants or other variables that can be used as markers for a particular phenotype. Reliable signature discovery methods could yield valuable insight into cell biology and mechanisms of human disease. However, it is currently not clear how to control error rates such as the false discovery rate (FDR in signature discovery. Moreover, signatures for cancer gene expression have been shown to be unstable, that is, difficult to replicate in independent studies, casting doubts on their reliability. Results We demonstrate that with modern prediction methods, signatures that yield accurate predictions may still have a high FDR. Further, we show that even signatures with low FDR may fail to replicate in independent studies due to limited statistical power. Thus, neither stability nor predictive accuracy are relevant when FDR control is the primary goal. We therefore develop a general statistical hypothesis testing framework that for the first time provides FDR control for signature discovery. Our method is demonstrated to be correct in simulation studies. When applied to five cancer data sets, the method was able to discover molecular signatures with 5% FDR in three cases, while two data sets yielded no significant findings. Conclusion Our approach enables reliable discovery of molecular signatures from genome-wide data with current sample sizes. The statistical framework developed herein is potentially applicable to a wide range of prediction problems in bioinformatics.

Resource Discovery in Activity-Based Sensor Networks

DEFF Research Database (Denmark)

Bucur, Doina; Bardram, Jakob

This paper proposes a service discovery protocol for sensor networks that is specifically tailored for use in humancentered pervasive environments. It uses the high-level concept of computational activities (as logical bundles of data and resources) to give sensors in Activity-Based Sensor Networks...... (ABSNs) knowledge about their usage even at the network layer. ABSN redesigns classical network-level service discovery protocols to include and use this logical structuring of the network for a more practically applicable service discovery scheme. Noting that in practical settings activity-based sensor...

Discovery and Innovation

African Journals Online (AJOL)

Discovery and Innovation is a journal of the African Academy of Sciences (AAS) ... World (TWAS) meant to focus attention on science and technology in Africa and the ... of Non-wood Forest Products: Potential Impacts and Challenges in Africa ...

Applications and Methods Utilizing the Simple Semantic Web Architecture and Protocol (SSWAP) for Bioinformatics Resource Discovery and Disparate Data and Service Integration

Science.gov (United States)

Scientific data integration and computational service discovery are challenges for the bioinformatic community. This process is made more difficult by the separate and independent construction of biological databases, which makes the exchange of scientific data between information resources difficu...

Biomarkers: in medicine, drug discovery, and environmental health

National Research Council Canada - National Science Library

Vaidya, Vishal S; Bonventre, Joseph V

2010-01-01

... Identification Using Mass Spectrometry Sample Preparation Protein Quantitation Examples of Biomarker Discovery and Evaluation Challenges in Proteomic Biomarker Discovery The Road Forward: Targeted ...

An Engineering Degree Does Not (Necessarily) an Engineer Make: Career Decision Making among Undergraduate Engineering Majors. Research Brief

Science.gov (United States)

Lichtenstein, Gary; Loshbaugh, Heidi G.; Claar, Brittany; Chen, Helen L.; Jackson, Kristyn; Sheppard, Sheri

2009-01-01

This paper explores the career-related decision making of seniors enrolled in undergraduate engineering programs at two nationally recognized institutions. This strand of the Academic Pathways Study (APS) research revealed that many engineering students were undecided about their career plans, even late into their senior years and that many were…

Multidimensional process discovery

NARCIS (Netherlands)

Ribeiro, J.T.S.

2013-01-01

Typically represented in event logs, business process data describe the execution of process events over time. Business process intelligence (BPI) techniques such as process mining can be applied to get strategic insight into business processes. Process discovery, conformance checking and

Generation of life in a test tube: Albert Szent-Gyorgyi, Bruno Straub, and the discovery of actin.

Science.gov (United States)

Rall, Jack A

2018-06-01

This is a story about a great scientist, luck, great discovery that changed the future direction of muscle research, war, a clandestine war mission, postwar politics, and an attempt to rewrite scientific history. Albert Szent-Gyorgyi, at 44 yr of age, won the Nobel Prize in 1937 for his work on vitamin C and the establishment of the groundwork of the citric acid cycle. He now wanted to investigate one of the fundamental aspects of life and settled on the study of muscle contraction. The Szent-Gyorgyi laboratory in Hungary during World War II demonstrated that contraction could be reproduced in vitro by threads consisting of just two proteins, myosin and the newly discovered protein by Bruno Straub that they called actin. Szent-Gyorgyi called seeing the contraction of these threads, which occurred in the presence of ATP and ions, "the most thrilling moment" of his scientific life. This major discovery of the generation of "life" in a test tube was totally unknown for years by the rest of the world because of the war. When the discovery was finally communicated to the world, it was not immediately accepted by all as being relevant to the physiology of muscle contraction. Nonetheless, this discovery opened up the modern phase of muscle research. Serendipity played an important role in the great discovery, and much later politics would lead to a shocking controversy around the true discoverer of actin.

History of the discovery of uranium fission by neutrons

International Nuclear Information System (INIS)

Simane, C.

1989-01-01

The history is briefly described of the discovery of uranium fission by neutrons, based on the texts of original scientific studies, memories or biographies of those who participated in the discovery and of their contemporaries. Obstacles that stood in the way of the discovery are discussed. It is stated that only a few scientists contributed to the discovery of uranium fission. The fission process itself still remains subject of physical research which studies its detailed laws. (Z.M.). 2 tabs., 16 refs

Discovery of the calcium, indium, tin, and platinum isotopes

International Nuclear Information System (INIS)

Amos, S.; Gross, J.L.; Thoennessen, M.

2011-01-01

Currently, twenty-four calcium, thirty-eight indium, thirty-eight tin, and thirty-nine platinum isotopes have been observed and the discovery of these isotopes is discussed here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented. - Highlights: Documentation of the discovery of all calcium, indium, tin and platinum isotopes. → Summary of author, journal, year, place and country of discovery for each isotope. → Brief description of discovery history of each isotope.

A Research on Reading Strategies among Non-English Major Postgraduates

Science.gov (United States)

Yang, Yang

2016-01-01

As a very important skill both in English teaching and learning, reading strategy has been emphasized at home and abroad for a long time. Many scholars and teachers make research on undergraduates of English major or non-English major. However, the postgraduates are often neglected. Actually, it is also imperative to make a study among…

Orphan diseases: state of the drug discovery art.

Science.gov (United States)

Volmar, Claude-Henry; Wahlestedt, Claes; Brothers, Shaun P

2017-06-01

Since 1983 more than 300 drugs have been developed and approved for orphan diseases. However, considering the development of novel diagnosis tools, the number of rare diseases vastly outpaces therapeutic discovery. Academic centers and nonprofit institutes are now at the forefront of rare disease R&D, partnering with pharmaceutical companies when academic researchers discover novel drugs or targets for specific diseases, thus reducing the failure risk and cost for pharmaceutical companies. Considerable progress has occurred in the art of orphan drug discovery, and a symbiotic relationship now exists between pharmaceutical industry, academia, and philanthropists that provides a useful framework for orphan disease therapeutic discovery. Here, the current state-of-the-art of drug discovery for orphan diseases is reviewed. Current technological approaches and challenges for drug discovery are considered, some of which can present somewhat unique challenges and opportunities in orphan diseases, including the potential for personalized medicine, gene therapy, and phenotypic screening.

Discovery learning with SAVI approach in geometry learning

Science.gov (United States)

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.

The Dynamic Radio Sky: An Opportunity for Discovery

Science.gov (United States)

2010-01-01

giant pulses from the Crab pulsar , a small number of dedicated radio transient surveys, and the serendipitous discovery of transient radio sources...used in the discovery of over 1800 radio pulsars . In 2003, the Parkes Multibeam Survey had covered the entire Galactic plane visible from Parkes... pulsars , and confirmed the neutron star nature of these sources, dubbed Rotating Radio Transients (RRATs). Since the discovery of the original 11 RRATs

Structural Genomics and Drug Discovery for Infectious Diseases

International Nuclear Information System (INIS)

Anderson, W.F.

2009-01-01

The application of structural genomics methods and approaches to proteins from organisms causing infectious diseases is making available the three dimensional structures of many proteins that are potential drug targets and laying the groundwork for structure aided drug discovery efforts. There are a number of structural genomics projects with a focus on pathogens that have been initiated worldwide. The Center for Structural Genomics of Infectious Diseases (CSGID) was recently established to apply state-of-the-art high throughput structural biology technologies to the characterization of proteins from the National Institute for Allergy and Infectious Diseases (NIAID) category A-C pathogens and organisms causing emerging, or re-emerging infectious diseases. The target selection process emphasizes potential biomedical benefits. Selected proteins include known drug targets and their homologs, essential enzymes, virulence factors and vaccine candidates. The Center also provides a structure determination service for the infectious disease scientific community. The ultimate goal is to generate a library of structures that are available to the scientific community and can serve as a starting point for further research and structure aided drug discovery for infectious diseases. To achieve this goal, the CSGID will determine protein crystal structures of 400 proteins and protein-ligand complexes using proven, rapid, highly integrated, and cost-effective methods for such determination, primarily by X-ray crystallography. High throughput crystallographic structure determination is greatly aided by frequent, convenient access to high-performance beamlines at third-generation synchrotron X-ray sources.

Progressively consolidating historical visual explorations for new discoveries

Science.gov (United States)

Zhao, Kaiyu; Ward, Matthew O.; Rundensteiner, Elke A.; Higgins, Huong N.

2013-12-01

A significant task within data mining is to identify data models of interest. While facilitating the exploration tasks, most visualization systems do not make use of all the data models that are generated during the exploration. In this paper, we introduce a system that allows the user to gain insights from the data space progressively by forming data models and consolidating the generated models on the fly. Each model can be a a computationally extracted or user-defined subset that contains a certain degree of interest and might lead to some discoveries. When the user generates more and more data models, the degree of interest of some portion of some models will either grow (indicating higher occurrence) or will fluctuate or decrease (corresponding to lower occurrence). Our system maintains a collection of such models and accumulates the interestingness of each model into a consolidated model. In order to consolidate the models, the system summarizes the associations between the models in the collection and identifies support (models reinforce each other), complementary (models complement each other), and overlap of the models. The accumulated interestingness keeps track of historical exploration and helps the user summarize their findings which can lead to new discoveries. This mechanism for integrating results from multiple models can be applied to a wide range of decision support systems. We demonstrate our system in a case study involving the financial status of US companies.

Discovery as a process

Energy Technology Data Exchange (ETDEWEB)

Loehle, C.

1994-05-01

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

A Hybrid Information Mining Approach for Knowledge Discovery in Cardiovascular Disease (CVD

Directory of Open Access Journals (Sweden)

Stefania Pasanisi

2018-04-01

Full Text Available The healthcare ambit is usually perceived as “information rich” yet “knowledge poor”. Nowadays, an unprecedented effort is underway to increase the use of business intelligence techniques to solve this problem. Heart disease (HD is a major cause of mortality in modern society. This paper analyzes the risk factors that have been identified in cardiovascular disease (CVD surveillance systems. The Heart Care study identifies attributes related to CVD risk (gender, age, smoking habit, etc. and other dependent variables that include a specific form of CVD (diabetes, hypertension, cardiac disease, etc.. In this paper, we combine Clustering, Association Rules, and Neural Networks for the assessment of heart-event-related risk factors, targeting the reduction of CVD risk. With the use of the K-means algorithm, significant groups of patients are found. Then, the Apriori algorithm is applied in order to understand the kinds of relations between the attributes within the dataset, first looking within the whole dataset and then refining the results through the subsets defined by the clusters. Finally, both results allow us to better define patients’ characteristics in order to make predictions about CVD risk with a Multilayer Perceptron Neural Network. The results obtained with the hybrid information mining approach indicate that it is an effective strategy for knowledge discovery concerning chronic diseases, particularly for CVD risk.

Testing jumps via false discovery rate control.

Directory of Open Access Journals (Sweden)

Yu-Min Yen

Full Text Available Many recently developed nonparametric jump tests can be viewed as multiple hypothesis testing problems. For such multiple hypothesis tests, it is well known that controlling type I error often makes a large proportion of erroneous rejections, and such situation becomes even worse when the jump occurrence is a rare event. To obtain more reliable results, we aim to control the false discovery rate (FDR, an efficient compound error measure for erroneous rejections in multiple testing problems. We perform the test via the Barndorff-Nielsen and Shephard (BNS test statistic, and control the FDR with the Benjamini and Hochberg (BH procedure. We provide asymptotic results for the FDR control. From simulations, we examine relevant theoretical results and demonstrate the advantages of controlling the FDR. The hybrid approach is then applied to empirical analysis on two benchmark stock indices with high frequency data.

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

Energy Technology Data Exchange (ETDEWEB)

Fox, Peter [Rensselaer Polytechnic Inst., Troy, NY (United States)

2015-05-30

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 current 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.

Discovery of the Largest Orbweaving Spider Species: The Evolution of Gigantism in Nephila

OpenAIRE

Kuntner, Matja?; Coddington, Jonathan A.

2009-01-01

Background More than 41,000 spider species are known with about 400?500 added each year, but for some well-known groups, such as the giant golden orbweavers, Nephila, the last valid described species dates from the 19th century. Nephila are renowned for being the largest web-spinning spiders, making the largest orb webs, and are model organisms for the study of extreme sexual size dimorphism (SSD) and sexual biology. Here, we report on the discovery of a new, giant Nephila species from Africa...

PENGEMBANGAN LKS DENGAN MODEL DISCOVERY LEARNING PADA MATERI IRISAN DUA LINGKARAN

Directory of Open Access Journals (Sweden)

Harisman Nizar

2016-07-01

Full Text Available This research aims at (1producing a valid and practical LKS (Student Worksheet in discovery learning model in two circles intersection material in class XI, and (2 to find out the potential effect toward the learning outcomes from the development of LKS with discovery learning model in two circles intersections material in class XI MIA. The design ofthis research is a developmental study. The subjects of this research were 33 students of XI MIA 1 SMA N 1 Indralaya in academic year 2015/2016. The data collecting technique used were observation, test, and interview. The result of the researches were : (1 This research produced a valid and practical LKS with discovery learning model in two circles intersections material in class XI MIA withsome characteristics such as, (a Contain the operational steps of discovery learning model, (b Help students in finding the concept of two circles intersections model. (c Make students active in learning. Being valid can be seen from the results of validator assessment, where the validator comments on the first prototype of LKS from content, construct, and language. Being practical can be seen from the results of  small group try out, in which it was based on analysis of the answer sheets of students, it was found that students were able to complete each steps there and students’ comments obtained from the sheets that stated the LKS given was easy to be done by students. (2 The developed LKS consisted of potential effect toward the learning outcomes from cognitive (knowledge, affective (attitude, and psychomotor (skill. In the cognitive domain 81.81% of students got score > 65, in the affective domain all of the students had shown an attitude of honesty and responsiveness shown by observations during LKS usage, as well as in the of psychomotor domain skills all of students had good skill that seen from the result of students performance.

The Higgs Boson Search and Discovery

CERN Document Server

Bernardi, Gregorio

2016-01-01

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

Discovery in a World of Mashups

Science.gov (United States)

King, T. A.; Ritschel, B.; Hourcle, J. A.; Moon, I. S.

2014-12-01

When the first digital information was stored electronically, discovery of what existed was through file names and the organization of the file system. With the advent of networks, digital information was shared on a wider scale, but discovery remained based on file and folder names. With a growing number of information sources, named based discovery quickly became ineffective. The keyword based search engine was one of the first types of a mashup in the world of Web 1.0. Embedded links from one document to another with prescribed relationships between files and the world of Web 2.0 was formed. Search engines like Google used the links to improve search results and a worldwide mashup was formed. While a vast improvement, the need for semantic (meaning rich) discovery was clear, especially for the discovery of scientific data. In response, every science discipline defined schemas to describe their type of data. Some core schemas where shared, but most schemas are custom tailored even though they share many common concepts. As with the networking of information sources, science increasingly relies on data from multiple disciplines. So there is a need to bring together multiple sources of semantically rich information. We explore how harvesting, conceptual mapping, facet based search engines, search term promotion, and style sheets can be combined to create the next generation of mashups in the emerging world of Web 3.0. We use NASA's Planetary Data System and NASA's Heliophysics Data Environment to illustrate how to create a multi-discipline mash-up.

Studying Scientific Discovery by Computer Simulation.

Science.gov (United States)

1983-03-30

Mendel’s laws of inheritance, the law of Gay- Lussac for gaseous reactions, tile law of Dulong and Petit, the derivation of atomic weights by Avogadro...neceseary mid identify by block number) scientific discovery -ittri sic properties physical laws extensive terms data-driven heuristics intensive...terms theory-driven heuristics conservation laws 20. ABSTRACT (Continue on revere. side It necessary and identify by block number) Scientific discovery

Fission and the discovery of isotopes

International Nuclear Information System (INIS)

Thoennessen, M.

2014-01-01

The discovery of new isotopes requires new developments in accelerator and detector technology. The new RI Beam Factory at RIKEN and the future projects FAIR at GSI and FRIB at MSU promise to expand the nuclear horizon even further. In the talk a short history of the role that fission played in the discovery of isotopes will be presented and future perspectives will be discussed

Major Risks, Uncertain Outcomes: Making Ensemble Forecasts Work for Multiple Audiences

Science.gov (United States)

Semmens, K. A.; Montz, B.; Carr, R. H.; Maxfield, K.; Ahnert, P.; Shedd, R.; Elliott, J.

2017-12-01

When extreme river levels are possible in a community, effective communication of weather and hydrologic forecasts is critical to protect life and property. Residents, emergency personnel, and water resource managers need to make timely decisions about how and when to prepare. Uncertainty in forecasting is a critical component of this decision-making, but often poses a confounding factor for public and professional understanding of forecast products. In 2016 and 2017, building on previous research about the use of uncertainty forecast products, and with funding from NOAA's CSTAR program, East Carolina University and Nurture Nature Center (a non-profit organization with a focus on flooding issues, based in Easton, PA) conducted a research project to understand how various audiences use and interpret ensemble forecasts showing a range of hydrologic forecast possibilities. These audiences include community residents, emergency managers and water resource managers. The research team held focus groups in Jefferson County, WV and Frederick County, MD, to test a new suite of products from the National Weather Service's Hydrologic Ensemble Forecast System (HEFS). HEFS is an ensemble system that provides short and long-range forecasts, ranging from 6 hours to 1 year, showing uncertainty in hydrologic forecasts. The goal of the study was to assess the utility of the HEFS products, identify the barriers to proper understanding of the products, and suggest modifications to product design that could improve the understandability and accessibility for residential, emergency managers, and water resource managers. The research team worked with the Sterling, VA Weather Forecast Office and the Middle Atlantic River Forecast center to develop a weather scenario as the basis of the focus group discussions, which also included pre and post session surveys. This presentation shares the findings from those focus group discussions and surveys, including recommendations for revisions to

Panorama 2017 - New conventional oil and gas discoveries

International Nuclear Information System (INIS)

Hureau, Geoffroy; Vially, Roland

2017-01-01

In 2016, spending on exploration is expected to decline by approximately 35% for the second consecutive year (total exploration-production is down 24%). However, volumes discovered through conventional exploration should only fall by 25% due to several significant discoveries, particularly in Alaska and West Africa. The largest discovery in 2016 was an unconventional Permian shale basin in the United States, which could alone contain as many hydrocarbons as all of the year's conventional discoveries combined

Developing integrated crop knowledge networks to advance candidate gene discovery.

Science.gov (United States)

Hassani-Pak, Keywan; Castellote, Martin; Esch, Maria; Hindle, Matthew; Lysenko, Artem; Taubert, Jan; Rawlings, Christopher

2016-12-01

The chances of raising crop productivity to enhance global food security would be greatly improved if we had a complete understanding of all the biological mechanisms that underpinned traits such as crop yield, disease resistance or nutrient and water use efficiency. With more crop genomes emerging all the time, we are nearer having the basic information, at the gene-level, to begin assembling crop gene catalogues and using data from other plant species to understand how the genes function and how their interactions govern crop development and physiology. Unfortunately, the task of creating such a complete knowledge base of gene functions, interaction networks and trait biology is technically challenging because the relevant data are dispersed in myriad databases in a variety of data formats with variable quality and coverage. In this paper we present a general approach for building genome-scale knowledge networks that provide a unified representation of heterogeneous but interconnected datasets to enable effective knowledge mining and gene discovery. We describe the datasets and outline the methods, workflows and tools that we have developed for creating and visualising these networks for the major crop species, wheat and barley. We present the global characteristics of such knowledge networks and with an example linking a seed size phenotype to a barley WRKY transcription factor orthologous to TTG2 from Arabidopsis, we illustrate the value of integrated data in biological knowledge discovery. The software we have developed (www.ondex.org) and the knowledge resources (http://knetminer.rothamsted.ac.uk) we have created are all open-source and provide a first step towards systematic and evidence-based gene discovery in order to facilitate crop improvement.

Virtual drug discovery: beyond computational chemistry?

Science.gov (United States)

Gilardoni, Francois; Arvanites, Anthony C

2010-02-01

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

Bioinformatics for discovery of microbiome variation

DEFF Research Database (Denmark)

Brejnrod, Asker Daniel

of various molecular methods to build hypotheses about the impact of a copper contaminated soil. The introduction is a broad introduction to the field of microbiome research with a focus on the technologies that enable these discoveries and how some of the broader issues have related to this thesis......Sequencing based tools have revolutionized microbiology in recent years. Highthroughput DNA sequencing have allowed high-resolution studies on microbial life in many different environments and at unprecedented low cost. These culture-independent methods have helped discovery of novel bacteria...... 1 ,“Large-scale benchmarking reveals false discoveries and count transformation sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome studies”, benchmarked the performance of a variety of popular statistical methods for discovering differentially abundant bacteria . between...

Reporting Astronomical Discoveries: Past, Now, and Future

Science.gov (United States)

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

2015-08-01

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

Discovery Of A Major Contradiction In Big Bang Cosmology Points To The New Cosmic Center Universe Model

CERN Document Server

Gentry, R V

2003-01-01

The BAL z=3.91 quasar's high Fe/O ratio has led to a reexamination of big bang's spacetime expansion postulate and the discovery that it predicts a CBR redshift of z>36000 instead of the widely accepted z~1000. This result leads an expansion-predicted CBR temperature of only T = 0.08K, which is contradicted by the experimental T = 2.73K. Contrary to long-held belief, these results strongly suggest that the F-L expanding spacetime paradigm, with its expansion redshifts, is not the correct relativistic description of the universe. This conclusion agrees with the earlier finding (gr-qc/9806061) that the universe is relativistically governed by the Einstein static spacetime solution of the field equations, not the F-L solution. Disproof of expansion redshifts removes the only support for the Cosmological Principle, thus showing that the spherical symmetry of the cosmos demanded by the Hubble redshift relation can no longer be attributed to the universe being the same everythere. The Cosmological Principle is flaw...

Matrix- and tensor-based recommender systems for the discovery of currently unknown inorganic compounds

Science.gov (United States)

Seko, Atsuto; Hayashi, Hiroyuki; Kashima, Hisashi; Tanaka, Isao

2018-01-01

Chemically relevant compositions (CRCs) and atomic arrangements of inorganic compounds have been collected as inorganic crystal structure databases. Machine learning is a unique approach to search for currently unknown CRCs from vast candidates. Herein we propose matrix- and tensor-based recommender system approaches to predict currently unknown CRCs from database entries of CRCs. Firstly, the performance of the recommender system approaches to discover currently unknown CRCs is examined. A Tucker decomposition recommender system shows the best discovery rate of CRCs as the majority of the top 100 recommended ternary and quaternary compositions correspond to CRCs. Secondly, systematic density functional theory (DFT) calculations are performed to investigate the phase stability of the recommended compositions. The phase stability of the 27 compositions reveals that 23 currently unknown compounds are newly found to be stable. These results indicate that the recommender system has great potential to accelerate the discovery of new compounds.

NASA Reverb: Standards-Driven Earth Science Data and Service Discovery

Science.gov (United States)

Cechini, M. F.; Mitchell, A.; Pilone, D.

2011-12-01

NASA's Earth Observing System Data and Information System (EOSDIS) is a core capability in NASA's Earth Science Data Systems Program. NASA's EOS ClearingHOuse (ECHO) is a metadata catalog for the EOSDIS, providing a centralized catalog of data products and registry of related data services. Working closely with the EOSDIS community, the ECHO team identified a need to develop the next generation EOS data and service discovery tool. This development effort relied on the following principles: + Metadata Driven User Interface - Users should be presented with data and service discovery capabilities based on dynamic processing of metadata describing the targeted data. + Integrated Data & Service Discovery - Users should be able to discovery data and associated data services that facilitate their research objectives. + Leverage Common Standards - Users should be able to discover and invoke services that utilize common interface standards. Metadata plays a vital role facilitating data discovery and access. As data providers enhance their metadata, more advanced search capabilities become available enriching a user's search experience. Maturing metadata formats such as ISO 19115 provide the necessary depth of metadata that facilitates advanced data discovery capabilities. Data discovery and access is not limited to simply the retrieval of data granules, but is growing into the more complex discovery of data services. These services include, but are not limited to, services facilitating additional data discovery, subsetting, reformatting, and re-projecting. The discovery and invocation of these data services is made significantly simpler through the use of consistent and interoperable standards. By utilizing an adopted standard, developing standard-specific adapters can be utilized to communicate with multiple services implementing a specific protocol. The emergence of metadata standards such as ISO 19119 plays a similarly important role in discovery as the 19115 standard

Accounting for discovery bias in genomic prediction

Science.gov (United States)

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

Discovery Monday - The Power to attract: Magnets that make heads turn

CERN Multimedia

2004-01-01

How do you steer particles round the LHC's 27 kilometre ring? How do you focus the particle beams in order to obtain collisions? How do you generate a magnetic field almost 200 000 times stronger than that of the Earth, using as little electricity as possible? By using superconducting magnets, of course! Come and discover the incredible properties of superconducting materials at Microcosm on Monday 7 June, where you will be able to try, among other things, to make a magnet levitate. You will also learn all you need to know about magnets and electromagnetism in general, thanks to some simple experiments. Come to the Microcosm on Monday 7 June, between 7.30 p.m. and 9.00 p.m. Entrance free. For further information see: http://www.cern.ch/microcosm

QSAR studies in the discovery of novel type-II diabetic therapies.

Science.gov (United States)

Abuhammad, Areej; Taha, Mutasem O

2016-01-01

Type-II diabetes mellitus (T2DM) is a complex chronic disease that represents a major therapeutic challenge. Despite extensive efforts in T2DM drug development, therapies remain unsatisfactory. Currently, there are many novel and important antidiabetic drug targets under investigation by many research groups worldwide. One of the main challenges to develop effective orally active hypoglycemic agents is off-target effects. Computational tools have impacted drug discovery at many levels. One of the earliest methods is quantitative structure-activity relationship (QSAR) studies. QSAR strategies help medicinal chemists understand the relationship between hypoglycemic activity and molecular properties. Hence, QSAR may hold promise in guiding the synthesis of specifically designed novel ligands that demonstrate high potency and target selectivity. This review aims to provide an overview of the QSAR strategies used to model antidiabetic agents. In particular, this review focuses on drug targets that raised recent scientific interest and/or led to successful antidiabetic agents in the market. Special emphasis has been made on studies that led to the identification of novel antidiabetic scaffolds. Computer-aided molecular design and discovery techniques like QSAR have a great potential in designing leads against complex diseases such as T2DM. Combined with other in silico techniques, QSAR can provide more useful and rational insights to facilitate the discovery of novel compounds. However, since T2DM is a complex disease that includes several faulty biological targets, multi-target QSAR studies are recommended in the future to achieve efficient antidiabetic therapies.

Weak affinity chromatography for evaluation of stereoisomers in early drug discovery.

Science.gov (United States)

Duong-Thi, Minh-Dao; Bergström, Maria; Fex, Tomas; Svensson, Susanne; Ohlson, Sten; Isaksson, Roland

2013-07-01

In early drug discovery (e.g., in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography-mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have a major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development.

Drugs from the Oceans: Marine Natural Products as Leads for Drug Discovery.

Science.gov (United States)

Altmann, Karl-Heinz

2017-10-25

The marine environment harbors a vast number of species that are the source of a wide array of structurally diverse bioactive secondary metabolites. At this point in time, roughly 27'000 marine natural products are known, of which eight are (were) at the origin of seven marketed drugs, mostly for the treatment of cancer. The majority of these drugs and also of drug candidates currently undergoing clinical evaluation (excluding antibody-drug conjugates) are unmodified natural products, but synthetic chemistry has played a central role in the discovery and/or development of all but one of the approved marine-derived drugs. More than 1000 new marine natural products have been isolated per year over the last decade, but the pool of new and unique structures is far from exhausted. To fully leverage the potential offered by the structural diversity of marine-produced secondary metabolites for drug discovery will require their broad assessment for different bioactivities and the productive interplay between new fermentation technologies, synthetic organic chemistry, and medicinal chemistry, in order to secure compound supply and enable lead optimization.

Knowledge Discovery from Vibration Measurements

Directory of Open Access Journals (Sweden)

Jun Deng

2014-01-01

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

Non-clinical influences on clinical decision-making: a major challenge to evidence-based practice.

Science.gov (United States)

Hajjaj, F M; Salek, M S; Basra, M K A; Finlay, A Y

2010-05-01

This article reviews an aspect of daily clinical practice which is of critical importance in virtually every clinical consultation, but which is seldom formally considered. Non-clinical influences on clinical decision-making profoundly affect medical decisions. These influences include patient-related factors such as socioeconomic status, quality of life and patient's expectations and wishes, physician-related factors such as personal characteristics and interaction with their professional community, and features of clinical practice such as private versus public practice as well as local management policies. This review brings together the different strands of knowledge concerning non-clinical influences on clinical decision-making. This aspect of decision-making may be the biggest obstacle to the reality of practising evidence-based medicine. It needs to be understood in order to develop clinical strategies that will facilitate the practice of evidence-based medicine.

The Discovery of Gravitational Repulsion by Johannes Droste

Science.gov (United States)

McGruder, Charles Hosewell; VanDerMeer, B. Wieb

2018-01-01

In 1687 Newton published his universal law of gravitation, which states that the gravitational force is always attractive. This law is based on our terrestrial experience with slowly moving bodies (v Einstein completed his theory of general relativity (also referred to as Einstein’s Theory of Gravitation), which is valid not just for slowly moving bodies but also for those with relativistic velocities. In 1916 Johannes Droste submitted a PhD thesis on general relativity to his advisor, H.A. Lorentz. In it he calculated the motion of a particle in what he called a “single center” and today we call the Schwarzschild field and found that highly relativistic particles experience gravitational repulsion. Thus, his thesis written in Dutch and never before translated contains the discovery of gravitational repulsion. Because of its historical importance we translate the entire section of his thesis containing the discovery of gravitational repulsion. We also translate his thesis in the hope of clearing up a major historical misconception. Namely, that David Hilbert in 1917 discovered gravitational repulsion. In fact, Hilbert rediscovered it, apparently completely independent of Droste’s work. Finally we note that one of the biggest mysteries of astrophysics is the question of how highly energetic particles in relativistic jets and cosmic rays are accelerated. It has been suggested that gravitational repulsion is the mechanism responsible for these phenomena. An historical understanding of gravitational repulsion is therefore pertinent.

A brief history of the ''Delayed'' discovery of nuclear fission

International Nuclear Information System (INIS)

Holden, N.E.

1989-08-01

This year marks the Fiftieth Anniversary of the discovery of Nuclear Fission. In the early 1930's, the neutron was discovered, followed by the discovery of artificial radioactivity and then the use of the neutron to produce artificial radioactivity. The first experiments resulting in the fission of uranium took place in 1934. A paper which speculated on fission as an explanation was almost immediately published, yet no one took it seriously not even the author herself. Why did it take an additional five years before anyone realized what had occurred? This is an abnormally long time in a period when discoveries, particularly in nuclear physics, seemed to be almost a daily occurrence. The events which led up to the discovery are recounted, with an attempt made to put them into their historical perspective. The role played by Mendeleev's Periodic Table, the role of the natural radioactive decay chain of uranium, the discovery of protactinium, the apparent discovery of masurium (technetium) and a speculation on the reason why Irene Curie may have missed the discovery of nuclear fission will all be discussed. 43 refs

Four disruptive strategies for removing drug discovery bottlenecks.

Science.gov (United States)

Ekins, Sean; Waller, Chris L; Bradley, Mary P; Clark, Alex M; Williams, Antony J

2013-03-01

Drug discovery is shifting focus from industry to outside partners and, in the process, creating new bottlenecks. Technologies like high throughput screening (HTS) have moved to a larger number of academic and institutional laboratories in the USA, with little coordination or consideration of the outputs and creating a translational gap. Although there have been collaborative public-private partnerships in Europe to share pharmaceutical data, the USA has seemingly lagged behind and this may hold it back. Sharing precompetitive data and models may accelerate discovery across the board, while finding the best collaborators, mining social media and mobile approaches to open drug discovery should be evaluated in our efforts to remove drug discovery bottlenecks. We describe four strategies to rectify the current unsustainable situation. Copyright © 2012 Elsevier Ltd. All rights reserved.

The discovery and development of uranium in Australia

International Nuclear Information System (INIS)

Glasson, K.R.

1988-01-01

The history of the discovery of Australia's uranium deposits is reviewed. The exploration can be conveniently divided into three periods - pre-1944, when the only significant discoveries were made by prospectors in South Australia at Radium Hill and Mount Painter; 1944-1960 and post-1967. The second period saw uranium discoveries in the Northern Territory and Queensland, most of which were made by prospectors using hand-held geiger counters and rewarded by the Australian Government. Since 1967 new deposits have been found in the Northern Territory, Queensland, South Australia and Western Australia by companies using maps, airborne radiometric surveys and sophisticated equipment. The step from the discovery of Mary Kathleen by prospectors to finding Roxby Downs by a combination of geophysical methods, geological concepts and deep drilling was a very big one

Applying Hierarchical Task Analysis Method to Discovery Layer Evaluation

Directory of Open Access Journals (Sweden)

Marlen Promann

2015-03-01

Full Text Available Libraries are implementing discovery layers to offer better user experiences. While usability tests have been helpful in evaluating the success or failure of implementing discovery layers in the library context, the focus has remained on its relative interface benefits over the traditional federated search. The informal site- and context specific usability tests have offered little to test the rigor of the discovery layers against the user goals, motivations and workflow they have been designed to support. This study proposes hierarchical task analysis (HTA as an important complementary evaluation method to usability testing of discovery layers. Relevant literature is reviewed for the discovery layers and the HTA method. As no previous application of HTA to the evaluation of discovery layers was found, this paper presents the application of HTA as an expert based and workflow centered (e.g. retrieving a relevant book or a journal article method to evaluating discovery layers. Purdue University’s Primo by Ex Libris was used to map eleven use cases as HTA charts. Nielsen’s Goal Composition theory was used as an analytical framework to evaluate the goal carts from two perspectives: a users’ physical interactions (i.e. clicks, and b user’s cognitive steps (i.e. decision points for what to do next. A brief comparison of HTA and usability test findings is offered as a way of conclusion.

Effects of Discovery, Iteration, and Collaboration in Laboratory Courses on Undergraduates' Research Career Intentions Fully Mediated by Student Ownership.

Science.gov (United States)

Corwin, Lisa A; Runyon, Christopher R; Ghanem, Eman; Sandy, Moriah; Clark, Greg; Palmer, Gregory C; Reichler, Stuart; Rodenbusch, Stacia E; Dolan, Erin L

2018-06-01

Course-based undergraduate research experiences (CUREs) provide a promising avenue to attract a larger and more diverse group of students into research careers. CUREs are thought to be distinctive in offering students opportunities to make discoveries, collaborate, engage in iterative work, and develop a sense of ownership of their lab course work. Yet how these elements affect students' intentions to pursue research-related careers remain unexplored. To address this knowledge gap, we collected data on three design features thought to be distinctive of CUREs (discovery, iteration, collaboration) and on students' levels of ownership and career intentions from ∼800 undergraduates who had completed CURE or inquiry courses, including courses from the Freshman Research Initiative (FRI), which has a demonstrated positive effect on student retention in college and in science, technology, engineering, and mathematics. We used structural equation modeling to test relationships among the design features and student ownership and career intentions. We found that discovery, iteration, and collaboration had small but significant effects on students' intentions; these effects were fully mediated by student ownership. Students in FRI courses reported significantly higher levels of discovery, iteration, and ownership than students in other CUREs. FRI research courses alone had a significant effect on students' career intentions.

Bigger Data, Collaborative Tools and the Future of Predictive Drug Discovery

Science.gov (United States)

Clark, Alex M.; Swamidass, S. Joshua; Litterman, Nadia; Williams, Antony J.

2014-01-01

Over the past decade we have seen a growth in the provision of chemistry data and cheminformatics tools as either free websites or software as a service (SaaS) commercial offerings. These have transformed how we find molecule-related data and use such tools in our research. There have also been efforts to improve collaboration between researchers either openly or through secure transactions using commercial tools. A major challenge in the future will be how such databases and software approaches handle larger amounts of data as it accumulates from high throughput screening and enables the user to draw insights, enable predictions and move projects forward. We now discuss how information from some drug discovery datasets can be made more accessible and how privacy of data should not overwhelm the desire to share it at an appropriate time with collaborators. We also discuss additional software tools that could be made available and provide our thoughts on the future of predictive drug discovery in this age of big data. We use some examples from our own research on neglected diseases, collaborations, mobile apps and algorithm development to illustrate these ideas. PMID:24943138

Efficient Certification Path Discovery for MANET

Directory of Open Access Journals (Sweden)

Kambourakis Georgios

2010-01-01

Full Text Available A Mobile Ad Hoc Network (MANET is characterized by the lack of any infrastructure, absence of any kind of centralized administration, frequent mobility of nodes, network partitioning, and wireless connections. These properties make traditional wireline security solutions not straightforwardly applicable in MANETs, and of course, constitute the establishment of a Public Key Infrastructure (PKI in such networks a cumbersome task. After surveying related work, we propose a novel public key management scheme using the well-known web-of-trust or trust graph model. Our scheme is based on a binary tree formation of the network's nodes. The binary tree structure is proved very effective for building certificate chains between communicating nodes that are multihops away and the cumbersome problem of certificate chain discovery is avoided. We compare our scheme with related work and show that it presents several advantages, especially when a fair balancing between security and performance is desirable. Simulations of the proposed scheme under different scenarios demonstrate that it is effective in terms of tree formation, join and leave occurrences, and certificate chain establishment.

Beyond discovery: A review of the critique of the discovery view of opportunities

DEFF Research Database (Denmark)

Korsgaard, Steffen T.

This paper systematically reviews and synthesises the critique since 2000 of the discovery view's interpretation of entrepreneurial opportunities. The review shows that the framing of the debate as polarised between two oppositions, the discovery view versus the creation view, is oversimplified....... The issue of whether opportunities are discovered or created is simply one of several key issues in play in the debate. These key issues include questions concerning agency, process, and the role of subjectivity, creativity and interpretation. Propositions for future research are developed from the critique......, emphasising distributed agency, non-linear processes, opportunities as formed, and the role of creativity. However, the paper also points to unresolved issues in relation to all four propositions that require further empirical and conceptual work....

MAGIC Database and Interfaces: An Integrated Package for Gene Discovery and Expression

Directory of Open Access Journals (Sweden)

Lee H. Pratt

2006-03-01

Full Text Available The rapidly increasing rate at which biological data is being produced requires a corresponding growth in relational databases and associated tools that can help laboratories contend with that data. With this need in mind, we describe here a Modular Approach to a Genomic, Integrated and Comprehensive (MAGIC Database. This Oracle 9i database derives from an initial focus in our laboratory on gene discovery via production and analysis of expressed sequence tags (ESTs, and subsequently on gene expression as assessed by both EST clustering and microarrays. The MAGIC Gene Discovery portion of the database focuses on information derived from DNA sequences and on its biological relevance. In addition to MAGIC SEQ-LIMS, which is designed to support activities in the laboratory, it contains several additional subschemas. The latter include MAGIC Admin for database administration, MAGIC Sequence for sequence processing as well as sequence and clone attributes, MAGIC Cluster for the results of EST clustering, MAGIC Polymorphism in support of microsatellite and single-nucleotide-polymorphism discovery, and MAGIC Annotation for electronic annotation by BLAST and BLAT. The MAGIC Microarray portion is a MIAME-compliant database with two components at present. These are MAGIC Array-LIMS, which makes possible remote entry of all information into the database, and MAGIC Array Analysis, which provides data mining and visualization. Because all aspects of interaction with the MAGIC Database are via a web browser, it is ideally suited not only for individual research laboratories but also for core facilities that serve clients at any distance.

Applications and methods utilizing the Simple Semantic Web Architecture and Protocol (SSWAP for bioinformatics resource discovery and disparate data and service integration

Directory of Open Access Journals (Sweden)

Nelson Rex T

2010-06-01

Full Text Available Abstract Background Scientific data integration and computational service discovery are challenges for the bioinformatic community. This process is made more difficult by the separate and independent construction of biological databases, which makes the exchange of data between information resources difficult and labor intensive. A recently described semantic web protocol, the Simple Semantic Web Architecture and Protocol (SSWAP; pronounced "swap" offers the ability to describe data and services in a semantically meaningful way. We report how three major information resources (Gramene, SoyBase and the Legume Information System [LIS] used SSWAP to semantically describe selected data and web services. Methods We selected high-priority Quantitative Trait Locus (QTL, genomic mapping, trait, phenotypic, and sequence data and associated services such as BLAST for publication, data retrieval, and service invocation via semantic web services. Data and services were mapped to concepts and categories as implemented in legacy and de novo community ontologies. We used SSWAP to express these offerings in OWL Web Ontology Language (OWL, Resource Description Framework (RDF and eXtensible Markup Language (XML documents, which are appropriate for their semantic discovery and retrieval. We implemented SSWAP services to respond to web queries and return data. These services are registered with the SSWAP Discovery Server and are available for semantic discovery at http://sswap.info. Results A total of ten services delivering QTL information from Gramene were created. From SoyBase, we created six services delivering information about soybean QTLs, and seven services delivering genetic locus information. For LIS we constructed three services, two of which allow the retrieval of DNA and RNA FASTA sequences with the third service providing nucleic acid sequence comparison capability (BLAST. Conclusions The need for semantic integration technologies has preceded

Novel dual small-molecule HIV inhibitors: scaffolds and discovery strategies.

Science.gov (United States)

Song, Anran; Yu, Haiqing; Wang, Changyuan; Zhu, Xingqi; Liu, Kexin; Ma, Xiaodong

2015-01-01

Searching for safe and effective treatments for HIV infection is still a great challenge worldwide in spite of the 27 marketed anti-HIV drugs and the powerful highly active antiretroviral therapy (HAART). As a promising prospect for generation of new HIV therapy drugs, multiple ligands (MDLs) were greatly focused on recently due to their lower toxicity, simplified dosing and patient adherence than single-target drugs. Till now, by disrupting two active sites or steps of HIV replications, a number of HIV dual inhibitors, such as CD4-gssucap120 inhibitors, CXCR4-gp20 inhibitors, RT-CXCR4 inhibitors, RT-protease inhibitors, RT-integrase inhibitors, and RTassociated functions inhibitors have been identified. Generally, these dual inhibitors were discovered mainly through screening approaches and design strategies. Of these compounds, the molecules bearing small skeletons exhibited strong anti-HIV activity and aroused great attention recently. Reviewing the progress of the dual small-molecule HIV inhibitors from the point of view of their scaffolds and discovery strategies will provide valuable information for producing more effective anti-HIV drugs. In this regard, novel dual small-molecule HIV inhibitors were illustrated, and their discovery paradigms as the major contents were also summarized in this manuscript.

Pharmacogenetics in type 2 diabetes: precision medicine or discovery tool?

Science.gov (United States)

Florez, Jose C

2017-05-01

In recent years, technological and analytical advances have led to an explosion in the discovery of genetic loci associated with type 2 diabetes. However, their ability to improve prediction of disease outcomes beyond standard clinical risk factors has been limited. On the other hand, genetic effects on drug response may be stronger than those commonly seen for disease incidence. Pharmacogenetic findings may aid in identifying new drug targets, elucidate pathophysiology, unravel disease heterogeneity, help prioritise specific genes in regions of genetic association, and contribute to personalised or precision treatment. In diabetes, precedent for the successful application of pharmacogenetic concepts exists in its monogenic subtypes, such as MODY or neonatal diabetes. Whether similar insights will emerge for the much more common entity of type 2 diabetes remains to be seen. As genetic approaches advance, the progressive deployment of candidate gene, large-scale genotyping and genome-wide association studies has begun to produce suggestive results that may transform clinical practice. However, many barriers to the translation of diabetes pharmacogenetic discoveries to the clinic still remain. This perspective offers a contemporary overview of the field with a focus on sulfonylureas and metformin, identifies the major uses of pharmacogenetics, and highlights potential limitations and future directions.

Major events and minor episodes

International Nuclear Information System (INIS)

Amaldi, U.

2014-01-01

Bruno Pontecorvo was a freshly graduated twenty one years old physicist when he joined, in the summer of 1934, the research group led by Enrico Fermi. In October the Panisperna boys would make their most important discovery – radioactivity induced by slow neutrons – and shortly thereafter would be parted by personal and historical events. This paper describes some episodes of those early years and of later periods, sketching a portrait of the team: starting from the extraordinary human and scientific experience of via Panisperna, up to the patent negotiations in USA, to which Pontecorvo’s flight to URSS put an end with unexpected consequences; getting to his first return in Italy, allowed by the sovietic government in 1978, on the occasion of the conference celebrating Edoardo Amaldi’s 70. anniversary. That was the first of several encounters of the author of this paper with Bruno Pontecorvo, which are here briefly recounted, as minor episodes giving a personal perspective on the man.

Discovery: Pile Patterns

Science.gov (United States)

de Mestre, Neville

2017-01-01

Earlier "Discovery" articles (de Mestre, 1999, 2003, 2006, 2010, 2011) considered patterns from many mathematical situations. This article presents a group of patterns used in 19th century mathematical textbooks. In the days of earlier warfare, cannon balls were stacked in various arrangements depending on the shape of the pile base…

A Metadata Schema for Geospatial Resource Discovery Use Cases

Directory of Open Access Journals (Sweden)

Darren Hardy

2014-07-01

Full Text Available We introduce a metadata schema that focuses on GIS discovery use cases for patrons in a research library setting. Text search, faceted refinement, and spatial search and relevancy are among GeoBlacklight's primary use cases for federated geospatial holdings. The schema supports a variety of GIS data types and enables contextual, collection-oriented discovery applications as well as traditional portal applications. One key limitation of GIS resource discovery is the general lack of normative metadata practices, which has led to a proliferation of metadata schemas and duplicate records. The ISO 19115/19139 and FGDC standards specify metadata formats, but are intricate, lengthy, and not focused on discovery. Moreover, they require sophisticated authoring environments and cataloging expertise. Geographic metadata standards target preservation and quality measure use cases, but they do not provide for simple inter-institutional sharing of metadata for discovery use cases. To this end, our schema reuses elements from Dublin Core and GeoRSS to leverage their normative semantics, community best practices, open-source software implementations, and extensive examples already deployed in discovery contexts such as web search and mapping. Finally, we discuss a Solr implementation of the schema using a "geo" extension to MODS.

Discovering non-random segregation of sister chromatids: The naïve treatment of a premature discovery

Directory of Open Access Journals (Sweden)

Karl G. Lark

2013-02-01

Full Text Available The discovery of non-random chromosome segregation is discussed from the perspective of what was known in1965 and1966. The distinction between daughter, parent or grandparent strands of DNA was developed in a bacterial system and led to the discovery that multiple copies of DNA elements of bacteria are not distributed randomly with respect to the age of the template strand. Experiments with higher eukaryotic cells demonstrated that during mitosis Mendel’s laws were violated; and the initial serendipitous choice of eukaryotic cell system led to the striking example of non-random segregation of parent and grand-parent DNA template strands in primary cultures of cells derived from mouse embryos. Attempts to extrapolate these findings to established TC lines demonstrated that the property could be lost. Experiments using plant root tips demonstrated that the phenomenon exists in plants and that it was, at some level, under genetic control. Despite publication in major journals and symposia (Lark et al. (1966a; Lark (1967a; 1967b; 1969, 1969a; 1969b the potential implications of these findings were ignored for several decades. Here we explore possible reasons for the pre-maturity (Stent, 1972 of this discovery.

Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

Science.gov (United States)

Semler, Matthew R; Wiseman, Roger W; Karl, Julie A; Graham, Michael E; Gieger, Samantha M; O'Connor, David H

2017-11-13

Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

Context-sensitive service discovery experimental prototype and evaluation

DEFF Research Database (Denmark)

Balken, Robin; Haukrogh, Jesper; L. Jensen, Jens

2007-01-01

The amount of different networks and services available to users today are increasing. This introduces the need for a way to locate and sort out irrelevant services in the process of discovering available services to a user. This paper describes and evaluates a prototype of an automated discovery...... and selection system, which locates services relevant to a user, based on his/her context and the context of the available services. The prototype includes a multi-level, hierarchical system approach and the introduction of entities called User-nodes, Super-nodes and Root-nodes. These entities separate...... the network in domains that handle the complex distributed service discovery, which is based on dynamically changing context information. In the prototype, a method for performing context-sensitive service discovery has been realised. The service discovery part utilizes UPnP, which has been expanded in order...

Nuclear fission - the unexpected discovery seventy years ago

International Nuclear Information System (INIS)

Weis, Michael

2008-01-01

Seventy years ago, on December 17, 1938, Otto Hahn, Lise Meitner, and Fritz Strassmann discovered nuclear fission. It was a serendipitous discovery resulting from the consistent pursuit, for many years, of occasionally unexpected radiochemical experimental findings. Hardly any other scientific discovery has had such direct bearing on our life, changing our view of the world. It over-threw the tenet of physics, believed to be incontestable, that the atom was indivisible. The use of nuclear power it has made possible has given rise to immense benefits, but it has also allowed mankind's most dreadful weapon so far to be developed. All this is ample reason seventy years later to recall the discovery, the discoverers and their times. It will also be shown what later generations have made of this discovery, and what economic and ecological prospects it continues to hold. (orig.)

Price discovery on the Johannesburg Stock Exchange: Examining ...

African Journals Online (AJOL)

Price discovery on the Johannesburg Stock Exchange: Examining the impact of the ... of price discovery aim to determine which market reflects new information first. ... This paper examines the FTSE/JSE Top 40 Index, the Top 40 Index Futures ...

Fateful discovery almost forgotten

CERN Multimedia

1989-01-01

"The discovery of the fission of uranium exactly half a century ago is at risk of passing unremarked because of the general ambivalence towards the consequences of this development. Can that be wise?" (4 pages)

Discovery of a Supernova Explosion at Half the Age of the Universe and its Cosmological Implications

Science.gov (United States)

Perlmutter, S.; Aldering, G.; Della Valle, M.; Deustua, S.; Ellis, R. S.; Fabbro, S.; Fruchter, A.; Goldhaber, G.; Goobar, A.; Groom, D. E.; Hook, I. M.; Kim, A. G.; Kim, M. Y.; Knop, R. A.; Lidman, C.; McMahon, R. G.; Nugent, P.; Pain, R.; Panagia, N.; Pennypacker, C. R.; Ruiz-Lapuente, P.; Schaefer, B.; Walton, N.

1997-12-16

The ultimate fate of the universe, infinite expansion or a big crunch, can be determined by measuring the redshifts, apparent brightnesses, and intrinsic luminosities of very distant supernovae. Recent developments have provided tools that make such a program practicable: (1) Studies of relatively nearby Type la supernovae (SNe la) have shown that their intrinsic luminosities can be accurately determined; (2) New research techniques have made it possible to schedule the discovery and follow-up observations of distant supernovae, producing well over 50 very distant (z = 0.3-0.7) SNe Ia to date. These distant supernovae provide a record of changes in the expansion rate over the past several billion years. By making precise measurements of supernovae at still greater distances, and thus extending this expansion history back far enough in time, we can even distinguish the slowing caused by the gravitational attraction of the universe's mass density {Omega}{sub M} from the effect of a possibly inflationary pressure caused by a cosmological constant {Lambda}. We report here the first such measurements, with our discovery of a Type Ia supernova (SN 1997ap) at z = 0.83. Measurements at the Keck II 10-m telescope make this the most distant spectroscopically confirmed supernova. Over two months of photometry of SN 1997ap with the Hubble Space Telescope and ground-based telescopes, when combined with previous measurements of nearer SNe la, suggests that we may live in a low mass-density universe. Further supernovae at comparable distances are currently scheduled for ground and space-based observations.

Simultaneous discovery, estimation and prediction analysis of complex traits using a bayesian mixture model.

Directory of Open Access Journals (Sweden)

Gerhard Moser

2015-04-01

Full Text Available Gene discovery, estimation of heritability captured by SNP arrays, inference on genetic architecture and prediction analyses of complex traits are usually performed using different statistical models and methods, leading to inefficiency and loss of power. Here we use a Bayesian mixture model that simultaneously allows variant discovery, estimation of genetic variance explained by all variants and prediction of unobserved phenotypes in new samples. We apply the method to simulated data of quantitative traits and Welcome Trust Case Control Consortium (WTCCC data on disease and show that it provides accurate estimates of SNP-based heritability, produces unbiased estimators of risk in new samples, and that it can estimate genetic architecture by partitioning variation across hundreds to thousands of SNPs. We estimated that, depending on the trait, 2,633 to 9,411 SNPs explain all of the SNP-based heritability in the WTCCC diseases. The majority of those SNPs (>96% had small effects, confirming a substantial polygenic component to common diseases. The proportion of the SNP-based variance explained by large effects (each SNP explaining 1% of the variance varied markedly between diseases, ranging from almost zero for bipolar disorder to 72% for type 1 diabetes. Prediction analyses demonstrate that for diseases with major loci, such as type 1 diabetes and rheumatoid arthritis, Bayesian methods outperform profile scoring or mixed model approaches.

An extended dual search space model of scientific discovery learning

NARCIS (Netherlands)

van Joolingen, Wouter; de Jong, Anthonius J.M.

1997-01-01

This article describes a theory of scientific discovery learning which is an extension of Klahr and Dunbar''s model of Scientific Discovery as Dual Search (SDDS) model. We present a model capable of describing and understanding scientific discovery learning in complex domains in terms of the SDDS

An explanation of resisted discoveries based on construal-level theory.

Science.gov (United States)

Fang, Hui

2015-02-01

New discoveries and theories are crucial for the development of science, but they are often initially resisted by the scientific community. This paper analyses resistance to scientific discoveries that supplement previous research results or conclusions with new phenomena, such as long chains in macromolecules, Alfvén waves, parity nonconservation in weak interactions and quasicrystals. Construal-level theory is used to explain that the probability of new discoveries may be underestimated because of psychological distance. Thus, the insufficiently examined scope of an accepted theory may lead to overstating the suitable scope and underestimating the probability of its undiscovered counter-examples. Therefore, psychological activity can result in people instinctively resisting new discoveries. Direct evidence can help people judge the validity of a hypothesis with rational thinking. The effects of authorities and textbooks on the resistance to discoveries are also discussed. From the results of our analysis, suggestions are provided to reduce resistance to real discoveries, which will benefit the development of science.

Introduction to fragment-based drug discovery.

Science.gov (United States)

Erlanson, Daniel A

2012-01-01

Fragment-based drug discovery (FBDD) has emerged in the past decade as a powerful tool for discovering drug leads. The approach first identifies starting points: very small molecules (fragments) that are about half the size of typical drugs. These fragments are then expanded or linked together to generate drug leads. Although the origins of the technique date back some 30 years, it was only in the mid-1990s that experimental techniques became sufficiently sensitive and rapid for the concept to be become practical. Since that time, the field has exploded: FBDD has played a role in discovery of at least 18 drugs that have entered the clinic, and practitioners of FBDD can be found throughout the world in both academia and industry. Literally dozens of reviews have been published on various aspects of FBDD or on the field as a whole, as have three books (Jahnke and Erlanson, Fragment-based approaches in drug discovery, 2006; Zartler and Shapiro, Fragment-based drug discovery: a practical approach, 2008; Kuo, Fragment based drug design: tools, practical approaches, and examples, 2011). However, this chapter will assume that the reader is approaching the field with little prior knowledge. It will introduce some of the key concepts, set the stage for the chapters to follow, and demonstrate how X-ray crystallography plays a central role in fragment identification and advancement.

Archeologia e Risorgimento. La scoperta degli Etruschi a Bologna / Archaeology and Risorgimento. The discovery of the Etruscans in Bologna

Directory of Open Access Journals (Sweden)

Sassatelli, Giuseppe

2011-10-01

Full Text Available During the italian Risorgimento and unification periods there was a link between the idea of national unity, the exploitation of urban identities and archeology, in particular the archeology of sites belonging to inhabitance of Italy in pre-Roman times. The discoveries concerning the Etruscans particularly influenced historical events and projects related to the future of the newly unified Italy. This paper analyzes the discovery of the Etruscans in Bologna and the consequences with respect to the foundation of the "Museo Civico Archeologico" (Civic Archaeological Museum, known as a major achievement in the city's history, which is aimed at defining and recovering an urban identity according to the the project of national unity.

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

Science.gov (United States)

Patel, Jigneshkumar

2013-03-01

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

The Discovery of Dabigatran Etexilate

Directory of Open Access Journals (Sweden)

Joanne evan Ryn

2013-02-01

Full Text Available Thromboembolic disease is a major cause of mortality and morbidity in the developed world and is caused by an excessive stimulation of coagulation. Thrombin is a key serine protease in the coagulation cascade and numerous efforts have been made to develop safe and effective orally active direct thrombin inhibitors (DTIs. Current anticoagulant therapy includes the use of indirect thrombin inhibitors (e.g. heparins, low-molecular-weight-heparins [LMWHs] and vitamin K antagonists (VKA such as warfarin. However there are several caveats in the clinical use of these agents including narrow therapeutic window, parenteral delivery, and food- and drug-drug interactions. Dabigatran is a synthetic, reversible DTI with high affinity and specificity for its target binding both free and clot-bound thrombin, and offers a favorable pharmacokinetic profile. Large randomized clinical trials have demonstrated that dabigatran provides comparable or superior thromboprophylaxis in multiple thromboembolic disease indications compared to standard of care. This minireview will highlight the discovery and development of dabigatran, the first in a class of new oral anticoagulant (NOAC agents to be licensed worldwide for the prevention of thromboembolism in the setting of orthopedic surgery and stroke prevent in atrial fibrillation.

The Implementation of Discovery Learning Model with Scientific Learning Approach to Improve Students’ Critical Thinking in Learning History

Directory of Open Access Journals (Sweden)

Edi Nurcahyo

2018-03-01

Full Text Available Historical learning has not reached optimal in the learning process. It is caused by the history teachers’ learning model has not used the innovative learning models. Furthermore, it supported by the perception of students to the history subject because it does not become final exam (UN subject so it makes less improvement and builds less critical thinking in students’ daily learning. This is due to the lack of awareness of historical events and the availability of history books for students and teachers in the library are still lacking. Discovery learning with scientific approach encourages students to solve problems actively and able to improve students' critical thinking skills with scientific approach so student can build scientific thinking include observing, asking, reasoning, trying, and networking   Keywords: discovery learning, scientific, critical thinking

Vylepšení nástroje ServiceNow Discovery v oblastech aplikačních vztahů a konfigurací aplikací

OpenAIRE

Toman, František

2014-01-01

The main focus of this paper is to improve the ServiceNow Discovery tool in two areas. The first one is the Application Dependency Mapping (ADM). ServiceNow is currently not able to determine the type of the relationship between two applications. As a solution, a new application was designed and implemented. It enables human element to define the type of relationship before it is found by the Discovery. This application also makes it posiible to define rules, which affect the behaviour of ADM...

Making public health nutrition relevant to evidence-based action.

OpenAIRE

Brunner, E.; Rayner, M.; Thorogood, M.; Margetts, B.; Hooper, L.; Summerbell, C.D.; Dowler, E.; Hewitt, G.; Robertson, A.; Wiseman, M.

2001-01-01

Public health nutrition enjoyed many breakthroughs in the\\ud 20th century – from the discovery of vitamins and the\\ud metabolic roles of some 60 macro- and micronutrients, to\\ud the effects of maternal and childhood diet on health over\\ud the life course. Moreover, the food shortages in the UK that\\ud were experienced during World War II gave the first\\ud opportunity to show that nutritional science could make a\\ud valuable contribution to public policy. However, public\\ud health nutrition is...

Taus and the Trigger for Discovery at ATLAS

International Nuclear Information System (INIS)

Demers, Sarah

2017-01-01

This five year grant allowed Yale Professor Sarah Demers and her students and postdocs to contribute to the ATLAS Experiment at CERN's Large Hadron Collider. We worked on a particular mode of the Higgs Boson decay, contributing to the discovery of this particle as well as measuring the particle's properties. We also performed a 'first of its kind' measurement at a hadron collider in the measurement of tau polarization, which increased the sensitivity of ATLAS in a number of exciting ways, both for making measurements of known particles and for hunting for new ones. We also contributed to the tau trigger - the real-time selection that chooses data that includes the signature of the tau lepton. Four PhD students in the Yale Physics Department received their PhDs during the term of this grant, with at least partial support from the grant.

Neutron Diffraction and Inorganic Materials Discovery

International Nuclear Information System (INIS)

Rosseinsky, M.J.

2005-01-01

Full text: The discovery of complex inorganic materials is an important academic and technological challenge because of the opportunities these systems offer for observation of new phenomena, and the questions they pose for fundamental understanding. This presentation will illustrate the key role of neutron powder diffraction in enabling the discovery of new classes of materials, and in evaluating their properties and the conditions under which they need to be processed to optimise their behaviour in devices for applications. New chemistry is illustrated by the transition metal oxide hydrides, where both structure and ionic mobility required neutron scattering characterisation. The relationship between chemistry, structure and properties will be addressed by considering the difficulties in inducing superconductivity in analogues of magnesium diboride. The role of both neutron and X-ray diffraction in evaluating the processing of microwave dielectric ceramics will be highlighted, with the discovery of new phases shown to be a useful bonus in this type of in-situ study. (author)

Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison.

Science.gov (United States)

Kazemian, Majid; Zhu, Qiyun; Halfon, Marc S; Sinha, Saurabh

2011-12-01

Despite recent advances in experimental approaches for identifying transcriptional cis-regulatory modules (CRMs, 'enhancers'), direct empirical discovery of CRMs for all genes in all cell types and environmental conditions is likely to remain an elusive goal. Effective methods for computational CRM discovery are thus a critically needed complement to empirical approaches. However, existing computational methods that search for clusters of putative binding sites are ineffective if the relevant TFs and/or their binding specificities are unknown. Here, we provide a significantly improved method for 'motif-blind' CRM discovery that does not depend on knowledge or accurate prediction of TF-binding motifs and is effective when limited knowledge of functional CRMs is available to 'supervise' the search. We propose a new statistical method, based on 'Interpolated Markov Models', for motif-blind, genome-wide CRM discovery. It captures the statistical profile of variable length words in known CRMs of a regulatory network and finds candidate CRMs that match this profile. The method also uses orthologs of the known CRMs from closely related genomes. We perform in silico evaluation of predicted CRMs by assessing whether their neighboring genes are enriched for the expected expression patterns. This assessment uses a novel statistical test that extends the widely used Hypergeometric test of gene set enrichment to account for variability in intergenic lengths. We find that the new CRM prediction method is superior to existing methods. Finally, we experimentally validate 12 new CRM predictions by examining their regulatory activity in vivo in Drosophila; 10 of the tested CRMs were found to be functional, while 6 of the top 7 predictions showed the expected activity patterns. We make our program available as downloadable source code, and as a plugin for a genome browser installed on our servers. © The Author(s) 2011. Published by Oxford University Press.

19 CFR 210.61 - Discovery and compulsory process.

Science.gov (United States)

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.

Science.gov (United States)

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...

Career Decision-making of Women's Junior College Students and Career Guidance : An Examination of Self-growth Motivation and Career Decision-making Self-efficacy

OpenAIRE

泉水, 清志; Sensui, Kiyoshi

2008-01-01

The purpose of this study was to examine effects of career decision-making by measuring self-growth motivation and career decision-making self-efficacy of women's junior college students, and to examine career guidance in junior college. A questionnaire was administered to 397, including 286 qualification major and 111 general education major, with women's junior college students. Results showed that self-growth motivation was higher with second-year and general education major students, that...

Use of combinatorial chemistry to speed drug discovery.

Science.gov (United States)

Rádl, S

1998-10-01

IBC's International Conference on Integrating Combinatorial Chemistry into the Discovery Pipeline was held September 14-15, 1998. The program started with a pre-conference workshop on High-Throughput Compound Characterization and Purification. The agenda of the main conference was divided into sessions of Synthesis, Automation and Unique Chemistries; Integrating Combinatorial Chemistry, Medicinal Chemistry and Screening; Combinatorial Chemistry Applications for Drug Discovery; and Information and Data Management. This meeting was an excellent opportunity to see how big pharma, biotech and service companies are addressing the current bottlenecks in combinatorial chemistry to speed drug discovery. (c) 1998 Prous Science. All rights reserved.

A cell-based fluorescent glucose transporter assay for SGLT2 inhibitor discovery

Directory of Open Access Journals (Sweden)

Yi Huan

2013-04-01

Full Text Available The sodium/glucose cotransporter 2 (SGLT2 is responsible for the majority of glucose reabsorption in the kidney, and currently, SGLT2 inhibitors are considered as promising hypoglycemic agents for the treatment of type 2 diabetes mellitus. By constructing CHO cell lines that stably express the human SGLT2 transmembrane protein, along with a fluorescent glucose transporter assay that uses 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-ylamino]2-deoxyglucose (2-NBDG as a glucose analog, we have developed a nonradioactive, cell-based assay for the discovery and characterization of SGLT2 inhibitors.

Discovery Monday - The Power to attract: Magnets that make heads turn

CERN Multimedia

2004-01-01

Model of a superconducting dipole magnet for the LHC project. How do you steer particles round the LHC's 27 kilometre ring? How do you focus the particle beams in order to obtain collisions? How do you generate a magnetic field almost 200 000 times stronger than that of the Earth, using as little electricity as possible? By using superconducting magnets, of course! Come and discover the incredible properties of superconducting materials at Microcosm on Monday 7 June, where you will be able to try, among other things, to make a magnet levitate. You will also learn all you need to know about magnets and electromagnetism in general, thanks to some simple experiments. Some 12 500 amperes, 30 000 times the strength of a 100-Watt electric light bulb, flow through the superconducting cable of the LHC's magnets without generating any resistance, and therefore with no loss of energy in the form of heat. There is just one problem. In order to function, the magnets have to be cooled to a temperature even colder than tha...

Discovery of the first selective inhibitor of excitatory amino acid transporter subtype 1

DEFF Research Database (Denmark)

Jensen, Anders Asbjørn; Erichsen, Mette Navy; Nielsen, Christina Wøhlk

2009-01-01

The discovery of the first class of subtype-selective inhibitors of the human excitatory amino acid transporter subtype 1 (EAAT1) and its rat orthologue GLAST is reported. An opening structure-activity relationship of 25 analogues is presented that addresses the influence of substitutions at the 4......- and 7-positions of the parental skeleton 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile. The most potent analogue 1o displays high nanomolar inhibitory activity at EAAT1 and a >400-fold selectivity over EAAT2 and EAAT3, making it a highly valuable pharmacological tool....