Portfolio management in early stage drug discovery - a traveler's guide through uncharted territory.

PubMed

Betz, Ulrich A K

2011-07-01

Portfolio management in drug development has become a best practice in the pharmaceutical industry. By contrast, early on in the value chain - the discovery phase - portfolio management is still in its infancy. Nevertheless, owing to the attrition of R&D projects from phase to phase and the cost of capital involved, these early phases of drug discovery play a significant part for the overall cost of bringing new, innovative drugs to the market. This paper describes various approaches to manage a portfolio of projects in early-stage drug discovery and provides crucial factors that determine the success of such an approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

SLAM, a Mathematica interface for SUSY spectrum generators

NASA Astrophysics Data System (ADS)

Marquard, Peter; Zerf, Nikolai

2014-03-01

We present and publish a Mathematica package, which can be used to automatically obtain any numerical MSSM input parameter from SUSY spectrum generators, which follow the SLHA standard, like SPheno, SOFTSUSY, SuSeFLAV or Suspect. The package enables a very comfortable way of numerical evaluations within the MSSM using Mathematica. It implements easy to use predefined high scale and low scale scenarios like mSUGRA or mhmax and if needed enables the user to directly specify the input required by the spectrum generators. In addition it supports an automatic saving and loading of SUSY spectra to and from a SQL data base, avoiding the rerun of a spectrum generator for a known spectrum. Catalogue identifier: AERX_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AERX_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 4387 No. of bytes in distributed program, including test data, etc.: 37748 Distribution format: tar.gz Programming language: Mathematica. Computer: Any computer where Mathematica version 6 or higher is running providing bash and sed. Operating system: Linux. Classification: 11.1. External routines: A SUSY spectrum generator such as SPheno, SOFTSUSY, SuSeFLAV or SUSPECT Nature of problem: Interfacing published spectrum generators for automated creation, saving and loading of SUSY particle spectra. Solution method: SLAM automatically writes/reads SLHA spectrum generator input/output and is able to save/load generated data in/from a data base. Restrictions: No general restrictions, specific restrictions are given in the manuscript. Running time: A single spectrum calculation takes much less than one second on a modern PC.

Stau coannihilation, compressed spectrum, and SUSY discovery potential at the LHC

NASA Astrophysics Data System (ADS)

Aboubrahim, Amin; Nath, Pran; Spisak, Andrew B.

2017-06-01

The lack of observation of supersymmetry thus far implies that the weak supersymmetry scale is larger than what was thought before the LHC era. This observation is strengthened by the Higgs boson mass measurement at ˜125 GeV , which within supersymmetric models implies a large loop correction and a weak supersymmetry scale lying in the several TeV region. In addition if neutralino is the dark matter, its relic density puts further constraints on models often requiring coannihilation to reduce the neutralino relic density to be consistent with experimental observation. The coannihilation in turn implies that the mass gap between the lightest supersymmetric particle and the next to lightest supersymmetric particle will be small, leading to softer final states and making the observation of supersymmetry challenging. In this work we investigate stau coannihilation models within supergravity grand unified models and the potential of discovery of such models at the LHC in the post-Higgs boson discovery era. We utilize a variety of signal regions to optimize the discovery of supersymmetry in the stau coannihilation region. In the analysis presented we impose the relic density constraint as well as the constraint of the Higgs boson mass. The range of sparticle masses discoverable up to the optimal integrated luminosity of the HL-LHC is investigated. It is found that the mass difference between the stau and the neutralino does not exceed ˜20 GeV over the entire mass range of the models explored. Thus the discovery of a supersymmetric signal arising from the stau coannihilation region will also provide a measurement of the neutralino mass. The direct detection of neutralino dark matter is analyzed within the class of stau coannihilation models investigated. The analysis is extended to include multiparticle coannihilation where stau along with chargino and the second neutralino enter into the coannihilation process.

Flow Cytometry: Impact On Early Drug Discovery

PubMed Central

Edwards, Bruce S.; Sklar, Larry A.

2015-01-01

Summary Modern flow cytometers can make optical measurements of 10 or more parameters per cell at tens-of-thousands of cells per second and over five orders of magnitude dynamic range. Although flow cytometry is used in most drug discovery stages, “sip-and-spit” sampling technology has restricted it to low sample throughput applications. The advent of HyperCyt sampling technology has recently made possible primary screening applications in which tens-of-thousands of compounds are analyzed per day. Target-multiplexing methodologies in combination with extended multi-parameter analyses enable profiling of lead candidates early in the discovery process, when the greatest numbers of candidates are available for evaluation. The ability to sample small volumes with negligible waste reduces reagent costs, compound usage and consumption of cells. Improved compound library formatting strategies can further extend primary screening opportunities when samples are scarce. Dozens of targets have been screened in 384- and 1536-well assay formats, predominantly in academic screening lab settings. In concert with commercial platform evolution and trending drug discovery strategies, HyperCyt-based systems are now finding their way into mainstream screening labs. Recent advances in flow-based imaging, mass spectrometry and parallel sample processing promise dramatically expanded single cell profiling capabilities to bolster systems level approaches to drug discovery. PMID:25805180

Prospects for axion detection in natural SUSY with mixed axion-higgsino dark matter: back to invisible?

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Baer, Howard; Serce, Hasan

2017-06-01

Under the expectation that nature is natural, we extend the Standard Model to include SUSY to stabilize the electroweak sector and PQ symmetry to stabilize the QCD sector. Then natural SUSY arises from a Kim-Nilles solution to the SUSY μ problem which allows for a little hierarchy where μ~ fa2/MP~ 100-300 GeV while the SUSY particle mass scale mSUSY~ 1-10 TeV gg μ. Dark matter then consists of two particles: a higgsino-like WIMP and a SUSY DFSZ axion. The range of allowed axion mass values ma depends on the mixed axion-higgsino relic density. The range of ma is actually restricted in this case by limits on WIMPs from direct and indirect detection experiments. We plot the expected axion detection rate at microwave cavity experiments. The axion-photon-photon coupling is severely diminished by charged higgsino contributions to the anomalous coupling. In this case, the axion may retreat, at least temporarily, back into the regime of near invisibility. From our results, we urge new ideas for techniques which probe both deeper and more broadly into axion coupling versus axion mass parameter space.

Holographic entanglement entropy and entanglement thermodynamics of 'black' non-susy D3 brane

NASA Astrophysics Data System (ADS)

Bhattacharya, Aranya; Roy, Shibaji

2018-06-01

Like BPS D3 brane, the non-supersymmetric (non-susy) D3 brane of type IIB string theory is also known to have a decoupling limit and leads to a non-supersymmetric AdS/CFT correspondence. The throat geometry in this case represents a QFT which is neither conformal nor supersymmetric. The 'black' version of the non-susy D3 brane in the decoupling limit describes a QFT at finite temperature. Here we first compute the entanglement entropy for small subsystem of such QFT from the decoupled geometry of 'black' non-susy D3 brane using holographic technique. Then we study the entanglement thermodynamics for the weakly excited states of this QFT from the asymptotically AdS geometry of the decoupled 'black' non-susy D3 brane. We observe that for small subsystem this background indeed satisfies a first law like relation with a universal (entanglement) temperature inversely proportional to the size of the subsystem and an (entanglement) pressure normal to the entangling surface. Finally we show how the entanglement entropy makes a cross-over to the thermal entropy at high temperature.

Flow Cytometry: Impact on Early Drug Discovery.

PubMed

Edwards, Bruce S; Sklar, Larry A

2015-07-01

Modern flow cytometers can make optical measurements of 10 or more parameters per cell at tens of thousands of cells per second and more than five orders of magnitude dynamic range. Although flow cytometry is used in most drug discovery stages, "sip-and-spit" sampling technology has restricted it to low-sample-throughput applications. The advent of HyperCyt sampling technology has recently made possible primary screening applications in which tens of thousands of compounds are analyzed per day. Target-multiplexing methodologies in combination with extended multiparameter analyses enable profiling of lead candidates early in the discovery process, when the greatest numbers of candidates are available for evaluation. The ability to sample small volumes with negligible waste reduces reagent costs, compound usage, and consumption of cells. Improved compound library formatting strategies can further extend primary screening opportunities when samples are scarce. Dozens of targets have been screened in 384- and 1536-well assay formats, predominantly in academic screening lab settings. In concert with commercial platform evolution and trending drug discovery strategies, HyperCyt-based systems are now finding their way into mainstream screening labs. Recent advances in flow-based imaging, mass spectrometry, and parallel sample processing promise dramatically expanded single-cell profiling capabilities to bolster systems-level approaches to drug discovery. © 2015 Society for Laboratory Automation and Screening.

Threshold corrections to dimension-six proton decay operators in SUSY SU(5)

NASA Astrophysics Data System (ADS)

Kuwahara, Takumi

2017-11-01

Proton decay is a significant phenomenon to verify supersymmetric grand unified theories (SUSY GUTs). To predict the proton lifetime precisely, it is important to include the next-leading order (NLO) corrections to the proton decay operators. In this talk, we have shown threshold corrections to the dimension-six proton decay operators in the minimal SUSY SU(5) GUT, its extended models with extra matters, and the missing partner SUSY SU(5) GUT. As a result, we have found that the threshold effects give rise to corrections a few percent in the minimal setup and below 5% in its extension with extra matters in spite of a large unified coupling at the GUT scale. On the other hand, in the missing partner model the correction to the proton decay rate is suppression about 60% due to a number of component fields of 75 and their mass splitting.

The BSM-AI project: SUSY-AI-generalizing LHC limits on supersymmetry with machine learning

NASA Astrophysics Data System (ADS)

Caron, Sascha; Kim, Jong Soo; Rolbiecki, Krzysztof; de Austri, Roberto Ruiz; Stienen, Bob

2017-04-01

A key research question at the Large Hadron Collider is the test of models of new physics. Testing if a particular parameter set of such a model is excluded by LHC data is a challenge: it requires time consuming generation of scattering events, simulation of the detector response, event reconstruction, cross section calculations and analysis code to test against several hundred signal regions defined by the ATLAS and CMS experiments. In the BSM-AI project we approach this challenge with a new idea. A machine learning tool is devised to predict within a fraction of a millisecond if a model is excluded or not directly from the model parameters. A first example is SUSY-AI, trained on the phenomenological supersymmetric standard model (pMSSM). About 300, 000 pMSSM model sets - each tested against 200 signal regions by ATLAS - have been used to train and validate SUSY-AI. The code is currently able to reproduce the ATLAS exclusion regions in 19 dimensions with an accuracy of at least 93%. It has been validated further within the constrained MSSM and the minimal natural supersymmetric model, again showing high accuracy. SUSY-AI and its future BSM derivatives will help to solve the problem of recasting LHC results for any model of new physics. SUSY-AI can be downloaded from http://susyai.hepforge.org/. An on-line interface to the program for quick testing purposes can be found at http://www.susy-ai.org/.

Coupled Boltzmann computation of mixed axion neutralino dark matter in the SUSY DFSZ axion model

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Baer, Howard; Lessa, Andre; Serce, Hasan

2014-10-01

The supersymmetrized DFSZ axion model is highly motivated not only because it offers solutions to both the gauge hierarchy and strong CP problems, but also because it provides a solution to the SUSY μ-problem which naturally allows for a Little Hierarchy. We compute the expected mixed axion-neutralino dark matter abundance for the SUSY DFSZ axion model in two benchmark cases—a natural SUSY model with a standard neutralino underabundance (SUA) and an mSUGRA/CMSSM model with a standard overabundance (SOA). Our computation implements coupled Boltzmann equations which track the radiation density along with neutralino, axion, axion CO (produced via coherent oscillations), saxion, saxion CO, axino and gravitino densities. In the SUSY DFSZ model, axions, axinos and saxions go through the process of freeze-in—in contrast to freeze-out or out-of-equilibrium production as in the SUSY KSVZ model—resulting in thermal yields which are largely independent of the re-heat temperature. We find the SUA case with suppressed saxion-axion couplings (ξ=0) only admits solutions for PQ breaking scale falesssim 6× 1012 GeV where the bulk of parameter space tends to be axion-dominated. For SUA with allowed saxion-axion couplings (ξ =1), then fa values up to ~ 1014 GeV are allowed. For the SOA case, almost all of SUSY DFSZ parameter space is disallowed by a combination of overproduction of dark matter, overproduction of dark radiation or violation of BBN constraints. An exception occurs at very large fa~ 1015-1016 GeV where large entropy dilution from CO-produced saxions leads to allowed models.

The impact of data integrity on decision making in early lead discovery

NASA Astrophysics Data System (ADS)

Beck, Bernd; Seeliger, Daniel; Kriegl, Jan M.

2015-09-01

Data driven decision making is a key element of today's pharmaceutical research, including early drug discovery. It comprises questions like which target to pursue, which chemical series to pursue, which compound to make next, or which compound to select for advanced profiling and promotion to pre-clinical development. In the following paper we will exemplify how data integrity, i.e. the context data is generated in and auxiliary information that is provided for individual result records, can influence decision making in early lead discovery programs. In addition we will describe some approaches which we pursue at Boehringer Ingelheim to reduce the risk for getting misguided.

Higgs mass corrections in the SUSY B - L model with inverse seesaw

NASA Astrophysics Data System (ADS)

Elsayed, A.; Khalil, S.; Moretti, S.

2012-08-01

In the context of the Supersymmetric (SUSY) B - L (Baryon minus Lepton number) model with inverse seesaw mechanism, we calculate the one-loop radiative corrections due to right-handed (s)neutrinos to the mass of the lightest Higgs boson when the latter is Standard Model (SM)-like. We show that such effects can be as large as O (100) GeV, thereby giving an absolute upper limit on such a mass around 180 GeV. The importance of this result from a phenomenological point of view is twofold. On the one hand, this enhancement greatly reconciles theory and experiment, by alleviating the so-called 'little hierarchy problem' of the minimal SUSY realization, whereby the current experimental limit on the SM-like Higgs mass is very near its absolute upper limit predicted theoretically, of 130 GeV. On the other hand, a SM-like Higgs boson with mass below 180 GeV is still well within the reach of the Large Hadron Collider (LHC), so that the SUSY realization discussed here is just as testable as the minimal version.

Gravity waves and the LHC: towards high-scale inflation with low-energy SUSY

NASA Astrophysics Data System (ADS)

He, Temple; Kachru, Shamit; Westphal, Alexander

2010-06-01

It has been argued that rather generic features of string-inspired inflationary theories with low-energy supersymmetry (SUSY) make it difficult to achieve inflation with a Hubble scale H > m 3/2, where m 3/2 is the gravitino mass in the SUSY-breaking vacuum state. We present a class of string-inspired supergravity realizations of chaotic inflation where a simple, dynamical mechanism yields hierarchically small scales of post-inflationary supersymmetry breaking. Within these toy models we can easily achieve small ratios between m 3/2 and the Hubble scale of inflation. This is possible because the expectation value of the superpotential < W> relaxes from large to small values during the course of inflation. However, our toy models do not provide a reasonable fit to cosmological data if one sets the SUSY-breaking scale to m 3/2 ≤ TeV. Our work is a small step towards relieving the apparent tension between high-scale inflation and low-scale supersymmetry breaking in string compactifications.

ADDME – Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective

PubMed Central

Tsaioun, Katya; Bottlaender, Michel; Mabondzo, Aloise

2009-01-01

The advent of early absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening has increased the attrition rate of weak drug candidates early in the drug-discovery process, and decreased the proportion of compounds failing in clinical trials for ADMET reasons. This paper reviews the history of ADMET screening and its place in pharmaceutical development, and central nervous system drug discovery in particular. Assays that have been developed in response to specific needs and improvements in technology that result in higher throughput and greater accuracy of prediction of human mechanisms of absorption and toxicity are discussed. The paper concludes with the authors' forecast of new models that will better predict human efficacy and toxicity. PMID:19534730

D-term contributions and CEDM constraints in E6 × SU(2)F × U(1)A SUSY GUT model

NASA Astrophysics Data System (ADS)

Shigekami, Yoshihiro

2017-11-01

We focus on E6 × SU(2)F × U(1)A supersymmetric (SUSY) grand unified theory (GUT) model. In this model, realistic Yukawa hierarchies and mixings are realized by introducing all allowed interactions with 𝓞(1) coefficients. Moreover, we can take stop mass is smaller than the other sfermion masses. This type of spectrum called by natural SUSY type sfermion mass spectrum can suppress the SUSY contributions to flavor changing neutral current (FCNC) and stabilize weak scale at the same time. However, light stop predicts large up quark CEDM and stop contributions are not decoupled. Since there is Kobayashi-Maskawa phase, stop contributions to the up quark CEDM is severely constrained even if all SUSY breaking parameters and Higgsino mass parameter μ are real. In this model, real up Yukawa couplings are realized at the GUT scale because of spontaneous CP violation. Therefore CEDM bounds are satisfied, although up Yukawa couplings are complex at the SUSY scale through the renormalization equation group effects. We calculated the CEDMs and found that EDM constraints can be satisfied even if stop mass is 𝓞(1) TeV. In addition, we investigate the size of D-terms in this model. Since these D-term contributions is flavor dependent, the degeneracy of sfermion mass spectrum is destroyed and the size of D-term is strongly constrained by FCNCs when SUSY breaking scale is the weak scale. However, SUSY breaking scale is larger than 1 TeV in order to obtain 125 GeV Higgs mass, and therefore sizable D-term contribution is allowed. Furthermore, we obtained the non-trivial prediction for the difference of squared sfermion mass.

Mixed axion/neutralino dark matter in the SUSY DFSZ axion model

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

Bae, Kyu Jung; Baer, Howard; Chun, Eung Jin, E-mail: bae@nhn.ou.edu, E-mail: baer@nhn.ou.edu, E-mail: ejchun@kias.re.kr

2013-12-01

We examine mixed axion/neutralino cold dark matter production in the SUSY DFSZ axion model where an axion superfield couples to Higgs superfields. We calculate a wide array of axino and saxion decay modes along with their decay temperatures, and thermal and non-thermal production rates. For a SUSY benchmark model with a standard underabundance (SUA) of Higgsino-like dark matter (DM), we find for the PQ scale f{sub a}∼<10{sup 12} GeV that the DM abundance is mainly comprised of axions as the saxion/axino decay occurs before the standard neutralino freeze-out and thus its abundance remains suppressed. For 10{sup 12}∼10{sup 14} GeV, bothmore » neutralino dark matter and dark radiation are typically overproduced. For judicious parameter choices, these can be suppressed and the combined neutralino/axion abundance brought into accord with measured values. A SUSY benchmark model with a standard overabundance (SOA) of bino DM is also examined and typically remains excluded due at least to too great a neutralino DM abundance for f{sub a}∼<10{sup 15} GeV. For f{sub a}∼>10{sup 15} GeV and lower saxion masses, large entropy production from saxion decay can dilute all relics and the SOA model can be allowed by all constraints.« less

FAST TRACK COMMUNICATION: SUSY transformations with complex factorization constants: application to spectral singularities

NASA Astrophysics Data System (ADS)

Samsonov, Boris F.

2010-10-01

Supersymmetric (SUSY) transformation operators with complex factorization constants are analyzed as operators acting in the Hilbert space of functions square integrable on the positive semiaxis. The obtained results are applied to Hamiltonians possessing spectral singularities which are non-Hermitian SUSY partners of self-adjoint operators. A new regularization procedure for the resolution of the identity operator in terms of a continuous biorthonormal set of the non-Hermitian Hamiltonian eigenfunctions is proposed. It is also argued that if the binorm of continuous spectrum eigenfunctions is interpreted in the same way as the norm of similar functions in the usual Hermitian case, then one can state that the function corresponding to a spectral singularity has zero binorm.

The hyperbolic step potential: Anti-bound states, SUSY partners and Wigner time delays

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

Gadella, M.; Kuru, Ş.; Negro, J., E-mail: jnegro@fta.uva.es

We study the scattering produced by a one dimensional hyperbolic step potential, which is exactly solvable and shows an unusual interest because of its asymmetric character. The analytic continuation of the scattering matrix in the momentum representation has a branch cut and an infinite number of simple poles on the negative imaginary axis which are related with the so called anti-bound states. This model does not show resonances. Using the wave functions of the anti-bound states, we obtain supersymmetric (SUSY) partners which are the series of Rosen–Morse II potentials. We have computed the Wigner reflection and transmission time delays formore » the hyperbolic step and such SUSY partners. Our results show that the more bound states a partner Hamiltonian has the smaller is the time delay. We also have evaluated time delays for the hyperbolic step potential in the classical case and have obtained striking similitudes with the quantum case. - Highlights: • The scattering matrix of hyperbolic step potential is studied. • The scattering matrix has a branch cut and an infinite number of poles. • The poles are associated to anti-bound states. • Susy partners using antibound states are computed. • Wigner time delays for the hyperbolic step and partner potentials are compared.« less

Should We Care that Johnny Can't Catch and Susie Can't Skip? What Should We Do about It?

ERIC Educational Resources Information Center

Whitall, Jill; Clark, Jane E.

2011-01-01

Physical and sport educators care that Johnny and Susie cannot move as well as their peers. They try their best to improve their skill levels because they value participation and skillfulness in sport and physical activity. However, many times there is a deeper problem as to why Johnny or Susie cannot move as well as their peers. Physical and…

On inflation, cosmological constant, and SUSY breaking

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

Linde, Andrei

2016-11-02

We consider a broad class of inflationary models of two unconstrained chiral superfields, the stabilizer S and the inflaton Φ, which can describe inflationary models with nearly arbitrary potentials. These models include, in particular, the recently introduced theories of cosmological attractors, which provide an excellent fit to the latest Planck data. We show that by adding to the superpotential of the fields S and Φ a small term depending on a nilpotent chiral superfield P one can break SUSY and introduce a small cosmological constant without affecting main predictions of the original inflationary scenario.

Comments on SUSY Inflation Models on the Brane

NASA Astrophysics Data System (ADS)

Lee, Lu-Yun; Cheung, Kingman; Lin, Chia-Min

In this paper we consider a class of inflation models on the brane where the dominant part of the inflaton scalar potential does not depend on the inflaton field value during inflation. In particular, we consider supernatural inflation, its hilltop version, A-term inflation, and supersymmetric (SUSY) D- and F-term hybrid inflation on the brane. We show that the parameter space can be broadened, the inflation scale generally can be lowered, and still possible to have the spectral index ns = 0.96.

SUSI 62 A Robust and Safe Parachute Uav with Long Flight Time and Good Payload

NASA Astrophysics Data System (ADS)

Thamm, H. P.

2011-09-01

In many research areas in the geo-sciences (erosion, land use, land cover change, etc.) or applications (e.g. forest management, mining, land management etc.) there is a demand for remote sensing images of a very high spatial and temporal resolution. Due to the high costs of classic aerial photo campaigns, the use of a UAV is a promising option for obtaining the desired remote sensed information at the time it is needed. However, the UAV must be easy to operate, safe, robust and should have a high payload and long flight time. For that purpose, the parachute UAV SUSI 62 was developed. It consists of a steel frame with a powerful 62 cm3 2- stroke engine and a parachute wing. The frame can be easily disassembled for transportation or to replace parts. On the frame there is a gimbal mounted sensor carrier where different sensors, standard SLR cameras and/or multi-spectral and thermal sensors can be mounted. Due to the design of the parachute, the SUSI 62 is very easy to control. Two different parachute sizes are available for different wind speed conditions. The SUSI 62 has a payload of up to 8 kg providing options to use different sensors at the same time or to extend flight duration. The SUSI 62 needs a runway of between 10 m and 50 m, depending on the wind conditions. The maximum flight speed is approximately 50 km/h. It can be operated in a wind speed of up to 6 m/s. The design of the system utilising a parachute UAV makes it comparatively safe as a failure of the electronics or the remote control only results in the UAV coming to the ground at a slow speed. The video signal from the camera, the GPS coordinates and other flight parameters are transmitted to the ground station in real time. An autopilot is available, which guarantees that the area of investigation is covered at the desired resolution and overlap. The robustly designed SUSI 62 has been used successfully in Europe, Africa and Australia for scientific projects and also for agricultural, forestry and

B Physics, Hg EDM, and Lepton Flavor Violation in SUSY Models

NASA Astrophysics Data System (ADS)

Shimizu, Yasuhiro

2005-06-01

We consider the correlation between the CP asymmetry in B → ϕKs (SϕKs) and the chromoelectric dipole moment (CEDM) of strange quark (dCs), which is constrained by the electric dipole moment (EDM) of 199Hg, is studied in the SUSY SU(5) GUT with right-handed neutrinos.

Discovery of a vezatin-like protein for dynein-mediated early endosome transport

PubMed Central

Yao, Xuanli; Arst, Herbert N.; Wang, Xiangfeng; Xiang, Xin

2015-01-01

Early endosomes are transported bidirectionally by cytoplasmic dynein and kinesin-3, but how the movements are regulated in vivo remains unclear. Here our forward genetic study led to the discovery of VezA, a vezatin-like protein in Aspergillus nidulans, as a factor critical for early endosome distribution. Loss of vezA causes an abnormal accumulation of early endosomes at the hyphal tip, where microtubule plus ends are located. This abnormal accumulation depends on kinesin-3 and is due to a decrease in the frequency but not the speed of dynein-mediated early endosome movement. VezA-GFP signals are enriched at the hypha tip in an actin-dependent manner but are not obviously associated with early endosomes, thus differing from the early endosome association of the cargo adapter HookA (Hook in A. nidulans). On loss of VezA, HookA associates normally with early endosomes, but the interaction between dynein-dynactin and the early-endosome-bound HookA is significantly decreased. However, VezA is not required for linking dynein-dynactin to the cytosolic ∆C-HookA, lacking the cargo-binding C-terminus. These results identify VezA as a novel regulator required for the interaction between dynein and the Hook-bound early endosomes in vivo. PMID:26378255

The early bird gets the worm: foraging strategies of wild songbirds lead to the early discovery of food sources

PubMed Central

Farine, Damien R.; Lang, Stephen D. J.

2013-01-01

Animals need to manage the combined risks of predation and starvation in order to survive. Theoretical and empirical studies have shown that individuals can reduce predation risk by delaying feeding (and hence fat storage) until late afternoon. However, little is known about how individuals manage the opposing pressures of resource uncertainty and predation risks. We suggest that individuals should follow a two-part strategy: prioritizing the discovery of food early in the day and exploiting the best patch late in the day. Using automated data loggers, we tested whether a temporal component exists in the discovery of novel foraging locations by individuals in a mixed-species foraging guild. We found that food deployed in the morning was discovered significantly more often than food deployed in the afternoon. Based on the diurnal activity patterns in this population, overall rates of new arrivals were also significantly higher than expected in the morning and significantly lower than expected in the afternoon. These results align with our predictions of a shift from patch discovery to exploitation over the course of the day. PMID:24108676

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection

Cancer.gov

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

Early Intervention System for Preschool Children with Autism in the Community: The DISCOVERY Approach in Yokohama, Japan.

ERIC Educational Resources Information Center

Honda, Hideo; Shimizu, Yasuo

2002-01-01

This article reports on DISCOVERY, a conceptual model for a clinical system of early detection and early intervention in cases of autism that has been implemented in Yokohama, Japan. Longitudinal data from 49 children who participated in a program during 1987-1990 indicate 32 were still being followed in 1999. (Contains references.) (Author/CR)

The Higgs and Supersymmetry at Run II of the LHC

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

Shih, David

2016-04-14

Prof. David Shih was supported by DOE grant DE-SC0013678 from April 2015 to April 2016. His research during this year focused on the phenomenology of super-symmetry (SUSY) and maximizing its future discovery potential at Run II of the LHC. SUSY is one of the most well-motivated frameworks for physics beyond the Standard Model. It solves the "naturalness" or "hierarchy" problem by stabilizing the Higgs mass against otherwise uncontrolled quantum corrections, predicts "grand unification" of the fundamental forces, and provides many potential candidates for dark matter. However, after decades of null results from direct and indirect searches, the viable parameter spacemore » for SUSY is increasingly constrained. Also, the discovery of a Standard Model-like Higgs with a mass at 125 GeV places a stringent constraint on SUSY models. In the work supported on this grant, Shih has worked on four different projects motivated by these issues. He has built natural SUSY models that explain the Higgs mass and provide viable dark matter; he has studied the parameter space of "gauge mediated supersymmetry breaking" (GMSB) that satisfies the Higgs mass constraint; he has developed new tools for the precision calculation of flavor and CP observables in general SUSY models; and he has studied new techniques for discovery of supersymmetric partners of the top quark.« less

Leptogenesis scenarios for natural SUSY with mixed axion-higgsino dark matter

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Baer, Howard; Serce, Hasan; Zhang, Yi-Fan

2016-01-01

Supersymmetric models with radiatively-driven electroweak naturalness require light higgsinos of mass ~ 100-300 GeV . Naturalness in the QCD sector is invoked via the Peccei-Quinn (PQ) axion leading to mixed axion-higgsino dark matter. The SUSY DFSZ axion model provides a solution to the SUSY μ problem and the Little Hierarchy μll m3/2 may emerge as a consequence of a mismatch between PQ and hidden sector mass scales. The traditional gravitino problem is now augmented by the axino and saxion problems, since these latter particles can also contribute to overproduction of WIMPs or dark radiation, or violation of BBN constraints. We compute regions of the TR vs. m3/2 plane allowed by BBN, dark matter and dark radiation constraints for various PQ scale choices fa. These regions are compared to the values needed for thermal leptogenesis, non-thermal leptogenesis, oscillating sneutrino leptogenesis and Affleck-Dine leptogenesis. The latter three are allowed in wide regions of parameter space for PQ scale fa~ 1010-1012 GeV which is also favored by naturalness: fa ~ √μMP/λμ ~ 1010-1012 GeV . These fa values correspond to axion masses somewhat above the projected ADMX search regions.

Early phase drug discovery: cheminformatics and computational techniques in identifying lead series.

PubMed

Duffy, Bryan C; Zhu, Lei; Decornez, Hélène; Kitchen, Douglas B

2012-09-15

Early drug discovery processes rely on hit finding procedures followed by extensive experimental confirmation in order to select high priority hit series which then undergo further scrutiny in hit-to-lead studies. The experimental cost and the risk associated with poor selection of lead series can be greatly reduced by the use of many different computational and cheminformatic techniques to sort and prioritize compounds. We describe the steps in typical hit identification and hit-to-lead programs and then describe how cheminformatic analysis assists this process. In particular, scaffold analysis, clustering and property calculations assist in the design of high-throughput screening libraries, the early analysis of hits and then organizing compounds into series for their progression from hits to leads. Additionally, these computational tools can be used in virtual screening to design hit-finding libraries and as procedures to help with early SAR exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

A continuous family of realistic SUSY SU(5) GUTs

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

Bajc, Borut, E-mail: borut.bajc@ijs.si

2016-06-21

It is shown that the minimal renormalizable supersymmetric SU(5) is still realistic providing the supersymmetric scale is at least few tens of TeV or large R-parity violating terms are considered. In the first case the vacuum is metastable, and different consistency constraints can give a bounded allowed region in the tan β − m{sub susy} plane. In the second case the mass eigenstate electron (down quark) is a linear combination of the original electron (down quark) and Higgsino (heavy colour triplet), and the mass ratio of bino and wino is determined. Both limits lead to light gravitino dark matter.

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

PubMed

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.

The ROTSE Supernova Verification Project (RSVP): Status and Early Discoveries

NASA Astrophysics Data System (ADS)

Yuan, Fang; Akerlof, C.; Quimby, R.; Aretakis, J.; McKay, T.; Miller, J. M.; Rykoff, E. S.; Swan, H. F.; Wheeler, J. C.

2007-12-01

The goal of the ROTSE Supernova Verification Project is the discovery of nearby supernova shortly after shock breakout followed by multi-epoch spectral observations as the lightcurves evolve. The very early spectra effectively constrain the progenitor properties and explosion models, but only a few such observations exist for SN Ia. The sequence of spectral observations reveals deeper and deeper layers of the explosion over time that can be used to construct a detailed picture of the burning process. This program follows the concept of the Texas Supernova Search initiated and executed successfully by Robert Quimby using ROTSE-IIIb at McDonald Observatory. To enlarge the discovery rate, we have developed image subtraction code to be installed on all four ROTSE-III telescopes. By monitoring selected fields nightly to a typical limiting magnitude of 18.5, ROTSE-III is able to discover a nearby supernova earlier than many similar searches. The expected discovery rate is 3 per month at one dedicated site. Since August 2007, our pipeline has been fully operational on ROTSE-IIIb and has discovered 5 supernovae, 3 of which we reported as ATELs and CBETs while the remaining two were found concurrently and reported by others. Among these, SN 2007if is a particularly interesting example of an apparent SN Ia involving the destruction of a super-Chandrasekhar mass system. Its spectrum closely matches that of SN 2003fg which was the first such case that has been observed. Our photometry data show a lightcurve that is a factor of 2 overluminous for a SN Ia, consistent with this interpretation. This work has been supported by NASA grants NNG-04WC41G and NNX-07AF02G.

Higgs, SUSY and the standard model at /γγ colliders

NASA Astrophysics Data System (ADS)

Hagiwara, Kaoru

2001-10-01

In this report, I surveyed physics potential of the γγ option of a linear e +e - collider with the following questions in mind: What new discovery can be expected at a γγ collider in addition to what will be learned at its ' parent' e +e -linear collider? By taking account of the hard energy spectrum and polarization of colliding photons, produced by Compton back-scattering of laser light off incoming e - beams, we find that a γγ collider is most powerful when new physics appears in the neutral spin-zero channel at an invariant mass below about 80% of the c.m. energy of the colliding e -e - system. If a light Higgs boson exists, its properties can be studied in detail, and if its heavier partners or a heavy Higgs boson exists in the above mass range, they may be discovered at a γγ collider. CP property of the scalar sector can be explored in detail by making use of linear polarization of the colliding photons, decay angular correlations of final state particles, and the pattern of interference with the Standard Model amplitudes. A few comments are given for SUSY particle studies at a γγ collider, where a pair of charged spinless particles is produced in the s-wave near the threshold. Squark-onium may be discovered. An e ±γ collision mode may measure the Higgs- Z-γ coupling accurately and probe flavor oscillations in the slepton sector. As a general remark, all the Standard Model background simulation tools should be prepared in the helicity amplitude level, so that simulation can be performed for an arbitrary set of Stokes parameters of the incoming photon beams.

Vacuum Stability in Split SUSY and Little Higgs Models

NASA Astrophysics Data System (ADS)

Datta, Alakabha; Zhang, Xinmin

We study the stability of the effective Higgs potential in the split supersymmetry and Little Higgs models. In particular, we study the effects of higher dimensional operators in the effective potential on the Higgs mass predictions. We find that the size and sign of the higher dimensional operators can significantly change the Higgs mass required to maintain vacuum stability in Split SUSY models. In the Little Higgs models the effects of higher dimensional operators can be large because of a relatively lower cutoff scale. Working with a specific model we find that a contribution from the higher dimensional operator with coefficient of O(1) can destabilize the vacuum.

Spontaneous parity violation and SUSY strong gauge theory

NASA Astrophysics Data System (ADS)

Haba, Naoyuki; Ohki, Hiroshi

2012-07-01

We suggest simple models of spontaneous parity violation in supersymmetric strong gauge theory. We focus on left-right symmetric model and investigate vacuum with spontaneous parity violation. Non-perturbative effects are calculable in supersymmetric gauge theory, and we suggest new models. Our models show confinement, so that we try to understand them by using a dual description of the theory. The left-right symmetry breaking and electroweak symmetry breaking are simultaneously occurred with the suitable energy scale hierarchy. This structure has several advantages compared to the MSSM. The scale of the Higgs mass (left-right breaking scale) and that of VEVs are different, so the SUSY little hierarchy problems are absent. The second model also induces spontaneous supersymmetry breaking [1].

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

PubMed

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.

Proteomic profiling in MPTP monkey model for early Parkinson disease biomarker discovery

PubMed Central

Lin, Xiangmin; Shi, Min; Gunasingh Masilamoni, Jeyaraj; Dator, Romel; Movius, James; Aro, Patrick; Smith, Yoland; Zhang, Jing

2015-01-01

Identification of reliable and robust biomarkers is crucial to enable early diagnosis of Parkinson disease (PD) and monitoring disease progression. While imperfect, the slow, chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced non-human primate animal model system of parkinsonism is an abundant source of pre-motor or early stage PD biomarker discovery. Here, we present a study of a MPTP rhesus monkey model of PD that utilizes complementary quantitative iTRAQ-based proteomic, glycoproteomics and phosphoproteomics approaches. We compared the glycoprotein, non-glycoprotein, and phosphoprotein profiles in the putamen of asymptomatic and symptomatic MPTP-treated monkeys as well as saline injected controls. We identified 86 glycoproteins, 163 non-glycoproteins, and 71 phosphoproteins differentially expressed in the MPTP-treated groups. Functional analysis of the data sets inferred the biological processes and pathways that link to neurodegeneration in PD and related disorders. Several potential biomarkers identified in this study have already been translated for their usefulness in PD diagnosis in human subjects and further validation investigations are currently under way. In addition to providing potential early PD biomarkers, this comprehensive quantitative proteomic study may also shed insights regarding the mechanisms underlying early PD development. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology. PMID:25617661

SUSY, the Third Generation and the LHC

NASA Astrophysics Data System (ADS)

Brust, Christopher; Katz, Andrey; Lawrence, Scott; Sundrum, Raman

2012-03-01

We develop a bottom-up approach to studying SUSY with light stops and sbottoms, but with other squarks and sleptons heavy and beyond reach of the LHC. We discuss the range of squark, gaugino and Higgsino masses for which the electroweak scale is radiatively stable over the "little hierarchy" below 10TeV. We review and expand on indirect constraints on this scenario, in particular from flavor and CP tests. We emphasize that in this context, R-parity violation is very well motivated. The phenomenological differences between Majorana and Dirac gauginos are also discussed. Finally, we focus on the light subsystem of stops, sbottom and neutralino with R-parity, in order to probe the current collider bounds. We find that 1/fb LHC bounds are mild and large parts of the motivated parameter space remain open, while the 10/fb data can be much more decisive.

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

PubMed

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

2017-11-06

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

Multiverse dark matter: SUSY or axions

NASA Astrophysics Data System (ADS)

D'Eramo, Francesco; Hall, Lawrence J.; Pappadopulo, Duccio

2014-11-01

The observed values of the cosmological constant and the abundance of Dark Matter (DM) can be successfully understood, using certain measures, by imposing the anthropic requirement that density perturbations go non-linear and virialize to form halos. This requires a probability distribution favoring low amounts of DM, i.e. low values of the PQ scale f for the QCD axion and low values of the superpartner mass scale for LSP thermal relics. In theories with independent scanning of multiple DM components, there is a high probability for DM to be dominated by a single component. For example, with independent scanning of f and , TeV-scale LSP DM and an axion solution to the strong CP problem are unlikely to coexist. With thermal LSP DM, the scheme allows an understanding of a Little SUSY Hierarchy with multi-TeV superpartners. Alternatively, with axion DM, PQ breaking before (after) inflation leads to f typically below (below) the projected range of the current ADMX experiment of f = (3 - 30) × 1011 GeV, providing strong motivation to develop experimental techniques for probing lower f.

Precision corrections to fine tuning in SUSY

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

Buckley, Matthew R.; Monteux, Angelo; Shih, David

Requiring that the contributions of supersymmetric particles to the Higgs mass are not highly tuned places upper limits on the masses of superpartners — in particular the higgsino, stop, and gluino. We revisit the details of the tuning calculation and introduce a number of improvements, including RGE resummation, two-loop effects, a proper treatment of UV vs. IR masses, and threshold corrections. This improved calculation more accurately connects the tuning measure with the physical masses of the superpartners at LHC-accessible energies. After these refinements, the tuning bound on the stop is now also sensitive to the masses of the 1st andmore » 2nd generation squarks, which limits how far these can be decoupled in Effective SUSY scenarios. We find that, for a fixed level of tuning, our bounds can allow for heavier gluinos and stops than previously considered. Despite this, the natural region of supersymmetry is under pressure from the LHC constraints, with high messenger scales particularly disfavored.« less

Precision corrections to fine tuning in SUSY

DOE PAGES

Buckley, Matthew R.; Monteux, Angelo; Shih, David

2017-06-20

Requiring that the contributions of supersymmetric particles to the Higgs mass are not highly tuned places upper limits on the masses of superpartners — in particular the higgsino, stop, and gluino. We revisit the details of the tuning calculation and introduce a number of improvements, including RGE resummation, two-loop effects, a proper treatment of UV vs. IR masses, and threshold corrections. This improved calculation more accurately connects the tuning measure with the physical masses of the superpartners at LHC-accessible energies. After these refinements, the tuning bound on the stop is now also sensitive to the masses of the 1st andmore » 2nd generation squarks, which limits how far these can be decoupled in Effective SUSY scenarios. We find that, for a fixed level of tuning, our bounds can allow for heavier gluinos and stops than previously considered. Despite this, the natural region of supersymmetry is under pressure from the LHC constraints, with high messenger scales particularly disfavored.« less

A Multicentre Audit of Single-Use Surgical Instruments (SUSI) for Tonsillectomy and Adenoidectomy

PubMed Central

O'Flynn, P; Silva, S; Kothari, P; Persaud, R

2007-01-01

INTRODUCTION Prions are resistant to conventional sterilisation procedures and, therefore, could be transmitted iatrogenically through re-usable adenoid and tonsil surgical instruments. Using disposable instruments would avoid the risk of transmission. We present the results of a complete audit loop using BBraun single-use surgical instruments (SUSI). PATIENTS AND METHODS This was a prospective multicentre audit. Surgeons were asked to fill in a standardised questionnaire recording details including postoperative complications, and evaluation of each piece of equipment compared with their own experience of conventional re-usable instruments. In the first cycle, constructive criticisms of the instruments were noted and the manufacturers modified the instruments accordingly. A second cycle of audit was subsequently undertaken. RESULTS A total of 86 patients were audited in the first cycle and 97 in the second cycle. Postoperative haemorrhage rate for both cycles was well within acceptable range. In the first audit cycle, surgeons generally found the Draffin rods, Boyle-Davis gag and bipolar diathermy forceps of poor quality and difficult to use. These were redesigned and, on repeat evaluation during the second audit cycle, were found to be just as good, if not better, than the re-usable instruments. CONCLUSIONS This study suggests that SUSI may be just as good as re-usable instruments. Furthermore, they may be more cost effective. PMID:18201478

Discovery on Pad 39a

NASA Image and Video Library

2010-10-31

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

Predictions from a flavour GUT model combined with a SUSY breaking sector

NASA Astrophysics Data System (ADS)

Antusch, Stefan; Hohl, Christian

2017-10-01

We discuss how flavour GUT models in the context of supergravity can be completed with a simple SUSY breaking sector, such that the flavour-dependent (non-universal) soft breaking terms can be calculated. As an example, we discuss a model based on an SU(5) GUT symmetry and A 4 family symmetry, plus additional discrete "shaping symmetries" and a ℤ 4 R symmetry. We calculate the soft terms and identify the relevant high scale input parameters, and investigate the resulting predictions for the low scale observables, such as flavour violating processes, the sparticle spectrum and the dark matter relic density.

Discovery Channel Telescope active optics system early integration and test

NASA Astrophysics Data System (ADS)

Venetiou, Alexander J.; Bida, Thomas A.

2012-09-01

The Discovery Channel Telescope (DCT) is a 4.3-meter telescope with a thin meniscus primary mirror (M1) and a honeycomb secondary mirror (M2). The optical design is an f/6.1 Ritchey-Chrétien (RC) with an unvignetted 0.5° Field of View (FoV) at the Cassegrain focus. We describe the design, implementation and performance of the DCT active optics system (AOS). The DCT AOS maintains collimation and controls the figure of the mirror to provide seeing-limited images across the focal plane. To minimize observing overhead, rapid settling times are achieved using a combination of feed-forward and low-bandwidth feedback control using a wavefront sensing system. In 2011, we mounted a Shack-Hartmann wavefront sensor at the prime focus of M1, the Prime Focus Test Assembly (PFTA), to test the AOS with the wavefront sensor, and the feedback loop. The incoming wavefront is decomposed using Zernike polynomials, and the mirror figure is corrected with a set of bending modes. Components of the system that we tested and tuned included the Zernike to Bending Mode transformations. We also started open-loop feed-forward coefficients determination. In early 2012, the PFTA was replaced by M2, and the wavefront sensor moved to its normal location on the Cassegrain instrument assembly. We present early open loop wavefront test results with the full optical system and instrument cube, along with refinements to the overall control loop operating at RC Cassegrain focus.

What hadron collider is required to discover or falsify natural supersymmetry?

NASA Astrophysics Data System (ADS)

Baer, Howard; Barger, Vernon; Gainer, James S.; Huang, Peisi; Savoy, Michael; Serce, Hasan; Tata, Xerxes

2017-11-01

Weak scale supersymmetry (SUSY) remains a compelling extension of the Standard Model because it stabilizes the quantum corrections to the Higgs and W , Z boson masses. In natural SUSY models these corrections are, by definition, never much larger than the corresponding masses. Natural SUSY models all have an upper limit on the gluino mass, too high to lead to observable signals even at the high luminosity LHC. However, in models with gaugino mass unification, the wino is sufficiently light that supersymmetry discovery is possible in other channels over the entire natural SUSY parameter space with no worse than 3% fine-tuning. Here, we examine the SUSY reach in more general models with and without gaugino mass unification (specifically, natural generalized mirage mediation), and show that the high energy LHC (HE-LHC), a pp collider with √{ s } = 33 TeV, will be able to detect the SUSY signal over the entire allowed mass range. Thus, HE-LHC would either discover or conclusively falsify natural SUSY with better than 3% fine-tuning using a conservative measure that allows for correlations among the model parameters.

Optimizing the discovery organization for innovation.

PubMed

Sams-Dodd, Frank

2005-08-01

Strategic management is the process of adapting organizational structure and management principles to fit the strategic goal of the business unit. The pharmaceutical industry has generally been expert at optimizing its organizations for drug development, but has rarely implemented different structures for the early discovery process, where the objective is innovation and the transformation of innovation into drug projects. Here, a set of strategic management methods is proposed, covering team composition, organizational structure, management principles and portfolio management, which are designed to increase the level of innovation in the early drug discovery process.

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

PubMed

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.

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

PubMed

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

2011-12-01

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

Weighted similarity-based clustering of chemical structures and bioactivity data in early drug discovery.

PubMed

Perualila-Tan, Nolen Joy; Shkedy, Ziv; Talloen, Willem; Göhlmann, Hinrich W H; Moerbeke, Marijke Van; Kasim, Adetayo

2016-08-01

The modern process of discovering candidate molecules in early drug discovery phase includes a wide range of approaches to extract vital information from the intersection of biology and chemistry. A typical strategy in compound selection involves compound clustering based on chemical similarity to obtain representative chemically diverse compounds (not incorporating potency information). In this paper, we propose an integrative clustering approach that makes use of both biological (compound efficacy) and chemical (structural features) data sources for the purpose of discovering a subset of compounds with aligned structural and biological properties. The datasets are integrated at the similarity level by assigning complementary weights to produce a weighted similarity matrix, serving as a generic input in any clustering algorithm. This new analysis work flow is semi-supervised method since, after the determination of clusters, a secondary analysis is performed wherein it finds differentially expressed genes associated to the derived integrated cluster(s) to further explain the compound-induced biological effects inside the cell. In this paper, datasets from two drug development oncology projects are used to illustrate the usefulness of the weighted similarity-based clustering approach to integrate multi-source high-dimensional information to aid drug discovery. Compounds that are structurally and biologically similar to the reference compounds are discovered using this proposed integrative approach.

Cosmic Noise: The Pioneers of Early Radio Astronomy and Their Discoveries

NASA Astrophysics Data System (ADS)

Sullivan, Woodruff T., III

2012-01-01

Extraterrestrial radio waves (the galactic background), often referred to as "cosmic noise", were first detected accidentally by Karl Jansky at a frequency of 20 MHz in 1932, with significant followup by Grote Reber. Yet after World War II it was England and Australia that dominated the field. An entirely different sky from that of visual astronomy was revealed by the discoveries of solar noise, "radio stars” (discrete sources such as Cas A, Tau A, Cyg A, Cen A and Vir A), galactic noise, lunar and meteor radar experiments, the detection of the 21 cm hydrogen line, and eventually optical identifications such as the Crab Nebula and M87. Key players included wartime radar experts such as Stanley Hey (the British Army's Operational Research Group), Martin Ryle (Cambridge University), Bernard Lovell (Jodrell Bank) and Joe Pawsey (Radiophysics Lab, Sydney). Younger leaders also emerged such as Graham Smith, Tony Hewish, John Davies, "Chris" Christiansen, Bernie Mills, Paul Wild, and John Bolton. Some optical astronomers (Jan Oort, Henk van de Hulst, Jesse Greenstein, Rudolph Minkowski, and Walter Baade) were also extremely supportive. By the end of the postwar decade, radio astronomy was firmly established within the gamut of astronomy, although very few of its practitioners had been trained as astronomers. I will also trace the technical and social aspects of this wholly new type of astronomy, with special attention on military and national influences. I argue that radio astronomy represents one of the key developments in twentieth century astronomy not only because of its own discoveries, but also its pathfinding for the further opening the electromagnetic spectrum. This study is based on exhaustive archival research and over one hundred interviews with pioneering radio astronomers. Full details are available in the book "Cosmic Noise: A History of Early Radio Astronomy" (Cambridge Univ. Pr.).

Search for beyond standard model physics (non-SUSY) in final states with photons at the Tevatron

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

Palencia, Jose Enrique; /Fermilab

2009-01-01

We present the results of searches for non-standard model phenomena in photon final states. These searches use data from integrated luminosities of {approx} 1-4 fb{sup -1} of p{bar p} collisions at {radical}s = 1.96 TeV, collected with the CDF and D0 detectors at the Fermilab Tevatron. No significant excess in data has been observed. We report limits on the parameters of several BSM models (excluding SUSY) for events containing photons.

Leptogenesis as an origin of hot dark matter and baryon asymmetry in the E6 inspired SUSY models

NASA Astrophysics Data System (ADS)

Nevzorov, R.

2018-04-01

We explore leptogenesis within the E6 inspired U (1) extension of the MSSM in which exact custodial symmetry forbids tree-level flavour-changing transitions and the most dangerous baryon and lepton number violating operators. This supersymmetric (SUSY) model involves extra exotic matter beyond the MSSM. In the simplest phenomenologically viable scenarios the lightest exotic fermions are neutral and stable. These states should be substantially lighter than 1eV forming hot dark matter in the Universe. The low-energy effective Lagrangian of the SUSY model under consideration possesses an approximate global U(1)E symmetry associated with the exotic states. The U(1)E symmetry is explicitly broken because of the interactions between the right-handed neutrino superfields and exotic matter supermultiplets. As a consequence the decays of the lightest right-handed neutrino/sneutrino give rise to both U(1)E and U(1) B - L asymmetries. When all right-handed neutrino/sneutrino are relatively light ∼106-107GeV the appropriate amount of the baryon asymmetry can be induced via these decays if the Yukawa couplings of the lightest right-handed neutrino superfields to the exotic matter supermultiplets vary between ∼10-4-10-3.

Sbottom discovery via mixed decays at the LHC

NASA Astrophysics Data System (ADS)

Han, Tao; Su, Shufang; Wu, Yongcheng; Zhang, Bin; Zhang, Huanian

2015-12-01

In the search for the bottom squark (sbottom) in supersymmetry (SUSY) at the LHC, the common practice has been to assume a 100% decay branching fraction for a given search channel. In realistic minimal supersymmetric Standard Model scenarios, there are often more than one significant decay modes to be present, which significantly weaken the current sbottom search limits at the LHC. On the other hand, the combination of the multiple decay modes offers alternative discovery channels for sbottom searches. In this paper, we present the sbottom decays in a few representative mass parameter scenarios. We then analyze the sbottom signal for the pair production in QCD with one sbottom decaying via b ˜ →b χ10 , b χ20 , and the other one decaying via b ˜→t χ1±. With the gaugino subsequent decaying to gauge bosons or a Higgs boson χ20→Z χ10 , h χ10 and χ1±→W±χ10, we study the reach of those signals at the 14 TeV LHC with 300 fb-1 integrated luminosity. For a left-handed bottom squark, we find that a mass up to 920 GeV can be discovered at 5 σ significance for 250 GeV 0 ); similarly, it can be discovered up to 840 GeV, or excluded up to 900 GeV at the 95% confidence level for the Z channel (μ <0 ). The top squark reach is close to that of the bottom squark. The sbottom and stop signals in the same SUSY parameter scenario are combined to obtain the optimal sensitivity, which is about 150 GeV better than the individual reach of the sbottom or stop. For a right-handed bottom squark with the b ˜ b˜ *→b χ10 , t χ1± channel, we find that the sbottom mass up to 880 GeV can be discovered at 5 σ significance, or excluded up to 1060 GeV at the 95% confidence level.

The Discovery of a Class of High-Temperature Superconductors.

ERIC Educational Resources Information Center

Muller, K. Alex; Bednorz, J. Georg

1987-01-01

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

Quasars at Cosmic Dawn: Discoveries and Probes of the Early Universe

NASA Astrophysics Data System (ADS)

Wang, Feige; Wu, Xue-Bing; Fan, Xiaohui; Yang, Jinyi; Bian, Fuyan; McGreer, Ian D.; Green, Richard F.; Yang, Qian; Jiang, Linhua; Wang, Ran; DECaLS Team; UHS Team

2017-01-01

High redshift quasars, as the most luminous non-transient objects in the early universe, are the most promising tracers to address the history of cosmic reionization and how the origins of super-massive black hole (SMBH) are linked to galaxy formation and evolution. Over the last fifteen years, more than 100 quasars within the first billion years after the Big Bang have been discovered with the highest redshift at 7.1. We have developed a new method to select z>~6 quasars with both high efficiency and high completeness by combing optical and mid-IR Wide-field Infrared Survey Explorer (WISE) photometric data. We have applied this method to SDSS footprint and resulted in the discovery of the most luminous z>6 quasar ever discovered, which hosts a twelve billion solar mass black hole. I will present detailed follow-up observations of the host galaxies and environment of the most luminous quasars using HST, LBT and ALMA, in order to constrain early black hole growth and black hole/galaxy co-evolution at the highest redshift. I will also present initial results from a new quasar survey, which utilizes optical data from DECaLS, which is imaging 6700 deg^2 of sky down to z_AB˜23.0, and neaar-IR data from UHS and UKIDSS, which maps the whole northern sky at Decl.<+60deg. The combination of these datasets allows us to discover quasars at redshift z>~7 and to conduct a complete census of the faint quasar population at z~6.

STS-128 Space Shuttle Discovery on Pad 39a

NASA Image and Video Library

2009-08-24

The space shuttle Discovery is poised for liftoff on the STS-128 mission from pad 39a at the Kennedy Space Center in Cape Canaveral, Fla., Monday, Aug. 24, 2009. Discovery is scheduled to launch early Tuesday morning. Photo Credit: (NASA/Bill Ingalls)

Bound state solution of Dirac equation for 3D harmonics oscillator plus trigonometric scarf noncentral potential using SUSY QM approach

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

Cari, C., E-mail: carinln@yahoo.com; Suparmi, A., E-mail: carinln@yahoo.com

2014-09-30

Dirac equation of 3D harmonics oscillator plus trigonometric Scarf non-central potential for spin symmetric case is solved using supersymmetric quantum mechanics approach. The Dirac equation for exact spin symmetry reduces to Schrodinger like equation. The relativistic energy and wave function for spin symmetric case are simply obtained using SUSY quantum mechanics method and idea of shape invariance.

Drug Discovery in Academia- the third way?

PubMed Central

Frearson, Julie; Wyatt, Paul

2010-01-01

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

In vitro transcriptomic prediction of hepatotoxicity for early drug discovery

PubMed Central

Cheng, Feng; Theodorescu, Dan; Schulman, Ira G.; Lee, Jae K.

2012-01-01

Liver toxicity (hepatotoxicity) is a critical issue in drug discovery and development. Standard preclinical evaluation of drug hepatotoxicity is generally performed using in vivo animal systems. However, only a small number of preselected compounds can be examined in vivo due to high experimental costs. A more efficient yet accurate screening technique which can identify potentially hepatotoxic compounds in the early stages of drug development would thus be valuable. Here, we develop and apply a novel genomic prediction technique for screening hepatotoxic compounds based on in vitro human liver cell tests. Using a training set of in vivo rodent experiments for drug hepatotoxicity evaluation, we discovered common biomarkers of drug-induced liver toxicity among six heterogeneous compounds. This gene set was further triaged to a subset of 32 genes that can be used as a multi-gene expression signature to predict hepatotoxicity. This multi-gene predictor was independently validated and showed consistently high prediction performance on five test sets of in vitro human liver cell and in vivo animal toxicity experiments. The predictor also demonstrated utility in evaluating different degrees of toxicity in response to drug concentrations which may be useful not only for discerning a compound’s general hepatotoxicity but also for determining its toxic concentration. PMID:21884709

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

DOE R&D Accomplishments Database

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.

Radiation Detection Material Discovery Initiative at PNNL

NASA Astrophysics Data System (ADS)

Milbrath, Brian

2006-05-01

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

Brane SUSY breaking and the gravitino mass

NASA Astrophysics Data System (ADS)

Kitazawa, Noriaki

2018-04-01

Supergravity models with spontaneously broken supersymmetry have been widely investigated over the years, together with some notable non-linear limits. Although in these models the gravitino becomes naturally massive absorbing the degrees of freedom of a Nambu-Goldstone fermion, there are cases in which the naive counting of degrees of freedom does not apply, in particular because of the absence of explicit gravitino mass terms in unitary gauge. The corresponding models require non-trivial de Sitter-like backgrounds, and it becomes of interest to clarify the fate of their Nambu-Goldstone modes. We elaborate on the fact that these non-trivial backgrounds can accommodate, consistently, gravitino fields carrying a number of degrees of freedom that is intermediate between those of massless and massive fields in a flat spacetime. For instance, in a simple supergravity model of this type with de Sitter background, the overall degrees of freedom of gravitino are as many as for a massive spin-3/2 field in flat spacetime, while the gravitino remains massless in the sense that it undergoes null-cone propagation in the stereographic picture. On the other hand, in the ten-dimensional USp(32) Type I Sugimoto model with "brane SUSY breaking", which requires a more complicated background, the degrees of freedom of gravitino are half as many of those of a massive one, and yet it somehow behaves again as a massless one.

Molecular Phenotyping Combines Molecular Information, Biological Relevance, and Patient Data to Improve Productivity of Early Drug Discovery.

PubMed

Drawnel, Faye Marie; Zhang, Jitao David; Küng, Erich; Aoyama, Natsuyo; Benmansour, Fethallah; Araujo Del Rosario, Andrea; Jensen Zoffmann, Sannah; Delobel, Frédéric; Prummer, Michael; Weibel, Franziska; Carlson, Coby; Anson, Blake; Iacone, Roberto; Certa, Ulrich; Singer, Thomas; Ebeling, Martin; Prunotto, Marco

2017-05-18

Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade. Copyright © 2017 Elsevier Ltd. All rights reserved.

Defining a discovery: priority and methodological controversy in early nineteenth-century anatomy

PubMed Central

Berkowitz, Carin

2014-01-01

In the early nineteenth century, Charles Bell and François Magendie engaged in a decades-long priority dispute over the discovery of the roots of motor and sensory nerves. The constantly recalibrated arguments of its participants illuminate changes in the life sciences during that period. When Bell first wrote about the nerves in 1811, surgeon-anatomists ran small schools out of their homes, natural theology was in vogue, exchanges between British and French medical practitioners were limited by the Napoleonic Wars, and British practitioners typically rejected experimental physiology and vivisection. By the end of Magendie's career, medical science was produced in the laboratory, taught through artfully produced performances of the sort at which Magendie excelled, and disseminated through journals. It is not entirely clear which historical character, Bell or Magendie, ‘won’ the dispute, nor that they even had clear and consistent positions in it, but what is clear is that one style of science had won out over the other, and over the course of the dispute, pedagogy lost pride of place in medical science. PMID:27494015

Cheminformatics in Drug Discovery, an Industrial Perspective.

PubMed

Chen, Hongming; Kogej, Thierry; Engkvist, Ola

2018-05-18

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

Doors to Discovery[TM]. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2007

2007-01-01

"Doors to Discovery"[TM] is an early childhood curriculum that uses thematic units to engage young children and support them as they build an understanding of their world. "Doors to Discovery"[TM] literacy activities are used to encourage children's development in a number of areas identified by research as the foundation for…

Approximation solution of Schrodinger equation for Q-deformed Rosen-Morse using supersymmetry quantum mechanics (SUSY QM)

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

Alemgadmi, Khaled I. K., E-mail: azozkied@yahoo.com; Suparmi; Cari

2015-09-30

The approximate analytical solution of Schrodinger equation for Q-Deformed Rosen-Morse potential was investigated using Supersymmetry Quantum Mechanics (SUSY QM) method. The approximate bound state energy is given in the closed form and the corresponding approximate wave function for arbitrary l-state given for ground state wave function. The first excited state obtained using upper operator and ground state wave function. The special case is given for the ground state in various number of q. The existence of Rosen-Morse potential reduce energy spectra of system. The larger value of q, the smaller energy spectra of system.

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

PubMed

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.

The discovery of the structure of DNA

NASA Astrophysics Data System (ADS)

Squires, G. L.

2003-04-01

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

The "Discovery" of Child Abuse

ERIC Educational Resources Information Center

Pfohl, Stephen J.

1977-01-01

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

Software automation tools for increased throughput metabolic soft-spot identification in early drug discovery.

PubMed

Zelesky, Veronica; Schneider, Richard; Janiszewski, John; Zamora, Ismael; Ferguson, James; Troutman, Matthew

2013-05-01

The ability to supplement high-throughput metabolic clearance data with structural information defining the site of metabolism should allow design teams to streamline their synthetic decisions. However, broad application of metabolite identification in early drug discovery has been limited, largely due to the time required for data review and structural assignment. The advent of mass defect filtering and its application toward metabolite scouting paved the way for the development of software automation tools capable of rapidly identifying drug-related material in complex biological matrices. Two semi-automated commercial software applications, MetabolitePilot™ and Mass-MetaSite™, were evaluated to assess the relative speed and accuracy of structural assignments using data generated on a high-resolution MS platform. Review of these applications has demonstrated their utility in providing accurate results in a time-efficient manner, leading to acceleration of metabolite identification initiatives while highlighting the continued need for biotransformation expertise in the interpretation of more complex metabolic reactions.

MLViS: A Web Tool for Machine Learning-Based Virtual Screening in Early-Phase of Drug Discovery and Development

PubMed Central

Korkmaz, Selcuk; Zararsiz, Gokmen; Goksuluk, Dincer

2015-01-01

Virtual screening is an important step in early-phase of drug discovery process. Since there are thousands of compounds, this step should be both fast and effective in order to distinguish drug-like and nondrug-like molecules. Statistical machine learning methods are widely used in drug discovery studies for classification purpose. Here, we aim to develop a new tool, which can classify molecules as drug-like and nondrug-like based on various machine learning methods, including discriminant, tree-based, kernel-based, ensemble and other algorithms. To construct this tool, first, performances of twenty-three different machine learning algorithms are compared by ten different measures, then, ten best performing algorithms have been selected based on principal component and hierarchical cluster analysis results. Besides classification, this application has also ability to create heat map and dendrogram for visual inspection of the molecules through hierarchical cluster analysis. Moreover, users can connect the PubChem database to download molecular information and to create two-dimensional structures of compounds. This application is freely available through www.biosoft.hacettepe.edu.tr/MLViS/. PMID:25928885

Cp Asymmetries of B → ϕK0 and B → η'KS Decays in SUSY Models

NASA Astrophysics Data System (ADS)

Dutta, Bhaskar; Kim, C. S.; Oh, Sechul; Zhu, Guohuai

2005-04-01

CP asymmetries of B → ϕK and B → η(')K modes are analyzed in the QCD improved factorization framework. The phenomenological parameters are determined from the global fit for the available B → PP and V P modes (without the subprocess b -> sbar {s}s). The possible deviation of sin(2ϕ1)ϕK0, η'Ks from sin(2ϕ1)J/ΨKs and the large branching ratio for B± → η'K± can be simultaneously explained in the context of R-parity conserving SUGRA models and R-parity violating SUSY models.

Discovery Orientation, Cognitive Schemas, and Disparities in Science Identity in Early Adolescence.

PubMed

Hill, Patricia Wonch; McQuillan, Julia; Spiegel, Amy N; Diamond, Judy

2018-02-01

Why are some youth more likely to think of themselves as a science kind of person than others? In this paper, we use a cognitive social-theoretical framework to assess disparities in science identity among middle school-age youth in the United States. We investigate how discovery orientation is associated with science interest, perceived ability, importance, and reflected appraisal, and how they are related to whether youth see themselves, and perceive that others see them, as a science kind of person. We surveyed 441 students in an ethnically diverse, low-income middle school. Gender and race/ethnicity are associated with science identity but not with discovery orientation. Structural equation model results show that the positive association between discovery orientation and science identity is mediated by science interest, importance, and reflected appraisal. These findings advance understanding of how science attitudes and recognition may contribute to the underrepresentation of girls and/or minorities in science.

Self-Discovery and Professional Development.

ERIC Educational Resources Information Center

Margolin, Edythe

This paper explores the role of self discovery in the early stages of caregiver professional development, with a focus on the array of choices available to university students. The assumption is that many people do not know their repertoire of skills until asked to complete a project requiring those skills; thus, "the heart of becoming a…

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates.

PubMed

Landis, Margaret S; Bhattachar, Shobha; Yazdanian, Mehran; Morrison, John

2018-01-01

This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

Alchemist multimodal workflows for diabetic retinopathy research, disease prevention and investigational drug discovery.

PubMed

Riposan, Adina; Taylor, Ian; Owens, David R; Rana, Omer; Conley, Edward C

2007-01-01

In this paper we present mechanisms for imaging and spectral data discovery, as applied to the early detection of pathologic mechanisms underlying diabetic retinopathy in research and clinical trial scenarios. We discuss the Alchemist framework, built using a generic peer-to-peer architecture, supporting distributed database queries and complex search algorithms based on workflow. The Alchemist is a domain-independent search mechanism that can be applied to search and data discovery scenarios in many areas. We illustrate Alchemist's ability to perform complex searches composed as a collection of peer-to-peer overlays, Grid-based services and workflows, e.g. applied to image and spectral data discovery, as applied to the early detection and prevention of retinal disease and investigational drug discovery. The Alchemist framework is built on top of decentralised technologies and uses industry standards such as Web services and SOAP for messaging.

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

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

Morton, M.J., E-mail: michael.morton@astrazeneca.com; Armstrong, D.; Abi Gerges, N.

2014-09-01

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity inmore » the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility.« less

Insecticide ADME for support of early-phase discovery: combining classical and modern techniques.

PubMed

David, Michael D

2017-04-01

The two factors that determine an insecticide's potency are its binding to a target site (intrinsic activity) and the ability of its active form to reach the target site (bioavailability). Bioavailability is dictated by the compound's stability and transport kinetics, which are determined by both physical and biochemical characteristics. At BASF Global Insecticide Research, we characterize bioavailability in early research with an ADME (Absorption, Distribution, Metabolism and Excretion) approach, combining classical and modern techniques. For biochemical assessment of metabolism, we purify native insect enzymes using classical techniques, and recombinantly express individual insect enzymes that are known to be relevant in insecticide metabolism and resistance. For analytical characterization of an experimental insecticide and its metabolites, we conduct classical radiotracer translocation studies when a radiolabel is available. In discovery, where typically no radiolabel has been synthesized, we utilize modern high-resolution mass spectrometry to probe complex systems for the test compounds and its metabolites. By using these combined approaches, we can rapidly compare the ADME properties of sets of new experimental insecticides and aid in the design of structures with an improved potential to advance in the research pipeline. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

New SPIRITS discoveries of Infrared Transients and Variables

NASA Astrophysics Data System (ADS)

Jencson, J. E.; Kasliwal, M. M.; Adams, S.; Cook, D.; Tinyanont, S.; Kwan, S.; Prince, T.; Lau, R. M.; Perley, D.; Masci, F.; Helou, G.; Armus, L.; Surace, J.; Dyk, S. D. Van; Cody, A.; Boyer, M. L.; Bond, H. E.; Monson, A.; Bally, J.; Khan, R.; Levesque, E.; Fox, O.; Williams, R.; Whitelock, P. A.; Mohamed, S.; Gehrz, R. D.; Amodeo, S.; Shenoy, D.; Carlon, R.; Cass, A.; Corgan, D.; Dykhoff, D.; Faella, J.; Gburek, T.; Smith, N.; Cantiello, M.; Langer, N.; Ofek, E.; Johansson, J.; Parthasarathy, M.; Hsiao, E.; Phillips, M.; Morrell, N.; Gonzalez, C.; Contreras, C.

2017-10-01

We report the discoveries of mid-infrared transients/strong variables found in the course of the Spitzer InfraRed Intensive Transients Survey (SPIRITS) using Spitzer Early Release Data (ATel #6644, #7929, #8688, #8940, #9434, #10171, #10172, #10488).

Early detection surveillance for an emerging plant pathogen: a rule of thumb to predict prevalence at first discovery

PubMed Central

Parnell, S.; Gottwald, T. R.; Cunniffe, N. J.; Alonso Chavez, V.; van den Bosch, F.

2015-01-01

Emerging plant pathogens are a significant problem for conservation and food security. Surveillance is often instigated in an attempt to detect an invading epidemic before it gets out of control. Yet in practice many epidemics are not discovered until already at a high prevalence, partly due to a lack of quantitative understanding of how surveillance effort and the dynamics of an invading epidemic relate. We test a simple rule of thumb to determine, for a surveillance programme taking a fixed number of samples at regular intervals, the distribution of the prevalence an epidemic will have reached on first discovery (discovery-prevalence) and its expectation E(q*). We show that E(q*) = r/(N/Δ), i.e. simply the rate of epidemic growth divided by the rate of sampling; where r is the epidemic growth rate, N is the sample size and Δ is the time between sampling rounds. We demonstrate the robustness of this rule of thumb using spatio-temporal epidemic models as well as data from real epidemics. Our work supports the view that, for the purposes of early detection surveillance, simple models can provide useful insights in apparently complex systems. The insight can inform decisions on surveillance resource allocation in plant health and has potential applicability to invasive species generally. PMID:26336177

Doors to Discovery [TM]. WWC Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2009

2009-01-01

Doors to Discovery[TM], an early childhood curriculum, focuses on the development of children's vocabulary and expressive and receptive language through a learning process called "shared literacy," where adults and children work together to develop literacy-related skills. Literacy activities, organized into thematic units, encourage children's…

Application of a High Throughput Method of Biomarker Discovery to Improvement of the EarlyCDT®-Lung Test

PubMed Central

Macdonald, Isabel K.; Murray, Andrea; Healey, Graham F.; Parsy-Kowalska, Celine B.; Allen, Jared; McElveen, Jane; Robertson, Chris; Sewell, Herbert F.; Chapman, Caroline J.; Robertson, John F. R.

2012-01-01

Background The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung) to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT. Recent advances in high throughput (HTP) cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV)). Methods and Findings Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165). Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7). Conclusion This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT­-Lung test, and so further aid the early detection of lung cancer. PMID:23272083

Substance Use and Sex Index (SUSI): First stage development of an assessment tool to measure behaviour change in sexualised drug use for substance use treatment studies.

PubMed

Ezard, Nadine; Webb, Beatrice; Clifford, Brendan; Cecilio, Michael E; Jellie, Amanda; Lea, Toby; Rodgers, Craig; Ruth, Simon; Bruno, Raimondo

2018-05-01

Existing tools for measuring blood-borne virus (BBV) and sexually transmitted infection (STI) transmission risk behaviours in substance use interventions have limited capacity to assess risk behaviours across varied social, cultural and epidemiological contexts; have not evolved alongside HIV treatment and prevention innovations; or accounted for sexual contexts of drug use including among a range of lesbian, gay, bisexual, transgender, intersex and queer (LGBTIQ) sub-communities. The Substance Use and Sex Index (SUSI) is a new brief, simple tool being developed to assess change in HIV and STI risk behaviours for substance use treatment studies. A 26-item questionnaire was piloted online among community volunteers (n = 199). Concurrent and predictive validity were assessed against risk-taking (RT-18) and STI testing items (Gay Community Periodic Surveys). The developed scale comprised nine items measuring: condomless penile (anal or vaginal) sex, unprotected oral sex, shared toy use, bloodplay, chemsex (consumption of drugs for the facilitation of sex), trading sex for drugs, being 'too out of it' to protect self, injecting risk and group sex. Factor-analytic approaches demonstrated that items met good fit criteria for a single scale. Significant, moderate magnitude, positive relationships were identified between total SUSI score and both RT-18 risk-taking and recent STI testing. Qualitative feedback underscored the importance of culturally-embedded question formulation. The results support the conceptual basis for the instrument, highlighting the need for further scale content refinement to validate the tool and examine sensitivity to change. SUSI is a step towards improving outcome measurement of HIV/BBV/STI transmission risk behaviours in substance use treatment studies with greater inclusiveness of experiences across different population groups. Copyright © 2018 Elsevier B.V. All rights reserved.

Stability of neutrino parameters and self-complementarity relation with varying SUSY breaking scale

NASA Astrophysics Data System (ADS)

Singh, K. Sashikanta; Roy, Subhankar; Singh, N. Nimai

2018-03-01

The scale at which supersymmetry (SUSY) breaks (ms) is still unknown. The present article, following a top-down approach, endeavors to study the effect of varying ms on the radiative stability of the observational parameters associated with the neutrino mixing. These parameters get additional contributions in the minimal supersymmetric model (MSSM). A variation in ms will influence the bounds for which the Standard Model (SM) and MSSM work and hence, will account for the different radiative contributions received from both sectors, respectively, while running the renormalization group equations (RGE). The present work establishes the invariance of the self complementarity relation among the three mixing angles, θ13+θ12≈θ23 against the radiative evolution. A similar result concerning the mass ratio, m2:m1 is also found to be valid. In addition to varying ms, the work incorporates a range of different seesaw (SS) scales and tries to see how the latter affects the parameters.

S-Duality, Deconstruction and Confinement for a Marginal Deformation of N=4 SUSY Yang-Mills

NASA Astrophysics Data System (ADS)

Dorey, Nick

2004-08-01

We study an exactly marginal deformation of Script N = 4 SUSY Yang-Mills with gauge group U(N) using field theory and string theory methods. The classical theory has a Higgs branch for rational values of the deformation parameter. We argue that the quantum theory also has an S-dual confining branch which cannot be seen classically. The low-energy effective theory on these branches is a six-dimensional non-commutative gauge theory with sixteen supercharges. Confinement of magnetic and electric charges, on the Higgs and confining branches respectively, occurs due to the formation of BPS-saturated strings in the low energy theory. The results also suggest a new way of deconstructing Little String Theory as a large-N limit of a confining gauge theory in four dimensions.

Early physics results.

PubMed

Jenni, Peter

2012-02-28

For the past year, experiments at the Large Hadron Collider (LHC) have started exploring physics at the high-energy frontier. Thanks to the superb turn-on of the LHC, a rich harvest of initial physics results have already been obtained by the two general-purpose experiments A Toroidal LHC Apparatus (ATLAS) and the Compact Muon Solenoid (CMS), which are the subject of this report. The initial data have allowed a test, at the highest collision energies ever reached in a laboratory, of the Standard Model (SM) of elementary particles, and to make early searches Beyond the Standard Model (BSM). Significant results have already been obtained in the search for the Higgs boson, which would establish the postulated electro-weak symmetry breaking mechanism in the SM, as well as for BSM physics such as Supersymmetry (SUSY), heavy new particles, quark compositeness and others. The important, and successful, SM physics measurements are giving confidence that the experiments are in good shape for their journey into the uncharted territory of new physics anticipated at the LHC.

Early detection surveillance for an emerging plant pathogen: a rule of thumb to predict prevalence at first discovery.

PubMed

Parnell, S; Gottwald, T R; Cunniffe, N J; Alonso Chavez, V; van den Bosch, F

2015-09-07

Emerging plant pathogens are a significant problem for conservation and food security. Surveillance is often instigated in an attempt to detect an invading epidemic before it gets out of control. Yet in practice many epidemics are not discovered until already at a high prevalence, partly due to a lack of quantitative understanding of how surveillance effort and the dynamics of an invading epidemic relate. We test a simple rule of thumb to determine, for a surveillance programme taking a fixed number of samples at regular intervals, the distribution of the prevalence an epidemic will have reached on first discovery (discovery-prevalence) and its expectation E(q*). We show that E(q*) = r/(N/Δ), i.e. simply the rate of epidemic growth divided by the rate of sampling; where r is the epidemic growth rate, N is the sample size and Δ is the time between sampling rounds. We demonstrate the robustness of this rule of thumb using spatio-temporal epidemic models as well as data from real epidemics. Our work supports the view that, for the purposes of early detection surveillance, simple models can provide useful insights in apparently complex systems. The insight can inform decisions on surveillance resource allocation in plant health and has potential applicability to invasive species generally. © 2015 The Author(s).

Analytical considerations for mass spectrometry profiling in serum biomarker discovery.

PubMed

Whiteley, Gordon R; Colantonio, Simona; Sacconi, Andrea; Saul, Richard G

2009-03-01

The potential of using mass spectrometry profiling as a diagnostic tool has been demonstrated for a wide variety of diseases. Various cancers and cancer-related diseases have been the focus of much of this work because of both the paucity of good diagnostic markers and the knowledge that early diagnosis is the most powerful weapon in treating cancer. The implementation of mass spectrometry as a routine diagnostic tool has proved to be difficult, however, primarily because of the stringent controls that are required for the method to be reproducible. The method is evolving as a powerful guide to the discovery of biomarkers that could, in turn, be used either individually or in an array or panel of tests for early disease detection. Using proteomic patterns to guide biomarker discovery and the possibility of deployment in the clinical laboratory environment on current instrumentation or in a hybrid technology has the possibility of being the early diagnosis tool that is needed.

Fossil evidence of avian crops from the Early Cretaceous of China

PubMed Central

Zheng, Xiaoting; Martin, Larry D.; Zhou, Zhonghe; Burnham, David A.; Zhang, Fucheng; Miao, Desui

2011-01-01

The crop is characteristic of seed-eating birds today, yet little is known about its early history despite remarkable discoveries of many Mesozoic seed-eating birds in the past decade. Here we report the discovery of some early fossil evidence for the presence of a crop in birds. Two Early Cretaceous birds, the basal ornithurine Hongshanornis and a basal avian Sapeornis, demonstrate that an essentially modern avian digestive system formed early in avian evolution. The discovery of a crop in two phylogenetically remote lineages of Early Cretaceous birds and its absence in most intervening forms indicates that it was independently acquired as a specialized seed-eating adaptation. Finally, the reduction or loss of teeth in the forms showing seed-filled crops suggests that granivory was possibly one of the factors that resulted in the reduction of teeth in early birds. PMID:21896733

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

PubMed

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

2012-08-01

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

Scientific workflows as productivity tools for drug discovery.

PubMed

Shon, John; Ohkawa, Hitomi; Hammer, Juergen

2008-05-01

Large pharmaceutical companies annually invest tens to hundreds of millions of US dollars in research informatics to support their early drug discovery processes. Traditionally, most of these investments are designed to increase the efficiency of drug discovery. The introduction of do-it-yourself scientific workflow platforms has enabled research informatics organizations to shift their efforts toward scientific innovation, ultimately resulting in a possible increase in return on their investments. Unlike the handling of most scientific data and application integration approaches, researchers apply scientific workflows to in silico experimentation and exploration, leading to scientific discoveries that lie beyond automation and integration. This review highlights some key requirements for scientific workflow environments in the pharmaceutical industry that are necessary for increasing research productivity. Examples of the application of scientific workflows in research and a summary of recent platform advances are also provided.

Discovery and History of Amino Acid Fermentation.

PubMed

Hashimoto, Shin-Ichi

There has been a strong demand in Japan and East Asia for L-glutamic acid as a seasoning since monosodium glutamate was found to present umami taste in 1907. The discovery of glutamate fermentation by Corynebacterium glutamicum in 1956 enabled abundant and low-cost production of the amino acid, creating a large market. The discovery also prompted researchers to develop fermentative production processes for other L-amino acids, such as lysine. Currently, the amino acid fermentation industry is so huge that more than 5 million metric tons of amino acids are manufactured annually all over the world, and this number continues to grow. Research on amino acid fermentation fostered the notion and skills of metabolic engineering which has been applied for the production of other compounds from renewable resources. The discovery of glutamate fermentation has had revolutionary impacts on both the industry and science. In this chapter, the history and development of glutamate fermentation, including the very early stage of fermentation of other amino acids, are reviewed.

Modern approaches to accelerate discovery of new antischistosomal drugs.

PubMed

Neves, Bruno Junior; Muratov, Eugene; Machado, Renato Beilner; Andrade, Carolina Horta; Cravo, Pedro Vitor Lemos

2016-06-01

The almost exclusive use of only praziquantel for the treatment of schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes. Consequently, there is an urgent need for new antischistosomal drugs. The identification of leads and the generation of high quality data are crucial steps in the early stages of schistosome drug discovery projects. Herein, the authors focus on the current developments in antischistosomal lead discovery, specifically referring to the use of automated in vitro target-based and whole-organism screens and virtual screening of chemical databases. They highlight the strengths and pitfalls of each of the above-mentioned approaches, and suggest possible roadmaps towards the integration of several strategies, which may contribute for optimizing research outputs and led to more successful and cost-effective drug discovery endeavors. Increasing partnerships and access to funding for drug discovery have strengthened the battle against schistosomiasis in recent years. However, the authors believe this battle also includes innovative strategies to overcome scientific challenges. In this context, significant advances of in vitro screening as well as computer-aided drug discovery have contributed to increase the success rate and reduce the costs of drug discovery campaigns. Although some of these approaches were already used in current antischistosomal lead discovery pipelines, the integration of these strategies in a solid workflow should allow the production of new treatments for schistosomiasis in the near future.

Simple animal models for amyotrophic lateral sclerosis drug discovery.

PubMed

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

2016-08-01

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

Antibody-enabled small-molecule drug discovery.

PubMed

Lawson, Alastair D G

2012-06-29

Although antibody-based therapeutics have become firmly established as medicines for serious diseases, the value of antibodies as tools in the early stages of small-molecule drug discovery is only beginning to be realized. In particular, antibodies may provide information to reduce risk in small-molecule drug discovery by enabling the validation of targets and by providing insights into the design of small-molecule screening assays. Moreover, antibodies can act as guides in the quest for small molecules that have the ability to modulate protein-protein interactions, which have traditionally only been considered to be tractable targets for biological drugs. The development of small molecules that have similar therapeutic effects to current biologics has the potential to benefit a broader range of patients at earlier stages of disease.

STS-33 Discovery, OV-103, early morning liftoff from KSC LC Pad 39B

NASA Image and Video Library

1989-11-22

STS033-S-003 (22 Nov 1989) --- The Space Shuttle Discovery heads for Earth-orbit on the first post-Challenger nocturnal launch. Liftoff occurred at 7:23:29:989 p.m. (EST), November 22, 1989. This picture shows almost a full front view of the Space Shuttle Discovery, its two Solid Rocket Boosters (SRB) and the External Tank (ET). Onboard for the Department of the Defense (DOD) devoted mission were astronauts Frederick D. Gregory, John E. Blaha, F. Story Musgrave, Kathryn C. Thornton and Manley L. Carter.

A Short History of the Discovery of Isotopes (and Some of Their Uses)

ERIC Educational Resources Information Center

Scott, Dave

2013-01-01

This article looks at the events that led to the discovery of isotopes in the early part of the 20th century. It is difficult to claim that the discovery was a single event. A number of famous scientists worked independently to provide the evidence, and the understanding of the need to think differently about atoms gradually emerged. Four varied…

A novel in silico approach to drug discovery via computational intelligence.

PubMed

Hecht, David; Fogel, Gary B

2009-04-01

A computational intelligence drug discovery platform is introduced as an innovative technology designed to accelerate high-throughput drug screening for generalized protein-targeted drug discovery. This technology results in collections of novel small molecule compounds that bind to protein targets as well as details on predicted binding modes and molecular interactions. The approach was tested on dihydrofolate reductase (DHFR) for novel antimalarial drug discovery; however, the methods developed can be applied broadly in early stage drug discovery and development. For this purpose, an initial fragment library was defined, and an automated fragment assembly algorithm was generated. These were combined with a computational intelligence screening tool for prescreening of compounds relative to DHFR inhibition. The entire method was assayed relative to spaces of known DHFR inhibitors and with chemical feasibility in mind, leading to experimental validation in future studies.

The A-Z of Zika drug discovery.

PubMed

Mottin, Melina; Borba, Joyce V V B; Braga, Rodolpho C; Torres, Pedro H M; Martini, Matheus C; Proenca-Modena, Jose Luiz; Judice, Carla C; Costa, Fabio T M; Ekins, Sean; Perryman, Alexander L; Andrade, Carolina Horta

2018-06-20

Despite the recent outbreak of Zika virus (ZIKV), there are still no approved treatments, and early-stage compounds are probably many years away from approval. A comprehensive A-Z review of the recent advances in ZIKV drug discovery efforts is presented, highlighting drug repositioning and computationally guided compounds, including discovered viral and host cell inhibitors. Promising ZIKV molecular targets are also described and discussed, as well as targets belonging to the host cell, as new opportunities for ZIKV drug discovery. All this knowledge is not only crucial to advancing the fight against the Zika virus and other flaviviruses but also helps us prepare for the next emerging virus outbreak to which we will have to respond. Copyright © 2018. Published by Elsevier Ltd.

Scientific Prediction and Prophetic Patenting in Drug Discovery.

PubMed

Curry, Stephen H; Schneiderman, Anne M

2015-01-01

Pharmaceutical patenting involves writing claims based on both discoveries already made, and on prophesy of future developments in an ongoing project. This is necessitated by the very different timelines involved in the drug discovery and product development process on the one hand, and successful patenting on the other. If patents are sought too early there is a risk that patent examiners will disallow claims because of lack of enablement. If patenting is delayed, claims are at risk of being denied on the basis of existence of prior art, because the body of relevant known science will have developed significantly while the project was being pursued. This review examines the role of prophetic patenting in relation to the essential predictability of many aspects of drug discovery science, promoting the concepts of discipline-related and project-related prediction. This is especially directed towards patenting activities supporting commercialization of academia-based discoveries, where long project timelines occur, and where experience, and resources to pay for patenting, are limited. The need for improved collaborative understanding among project scientists, technology transfer professionals in, for example, universities, patent attorneys, and patent examiners is emphasized.

"Seeing is believing": perspectives of applying imaging technology in discovery toxicology.

PubMed

Xu, Jinghai James; Dunn, Margaret Condon; Smith, Arthur Russell

2009-11-01

Efficiency and accuracy in addressing drug safety issues proactively are critical in minimizing late-stage drug attritions. Discovery toxicology has become a specialty subdivision of toxicology seeking to effectively provide early predictions and safety assessment in the drug discovery process. Among the many technologies utilized to select safer compounds for further development, in vitro imaging technology is one of the best characterized and validated to provide translatable biomarkers towards clinically-relevant outcomes of drug safety. By carefully applying imaging technologies in genetic, hepatic, and cardiac toxicology, and integrating them with the rest of the drug discovery processes, it was possible to demonstrate significant impact of imaging technology on drug research and development and substantial returns on investment.

STS-33 Discovery, OV-103, early morning liftoff from KSC LC Pad 39B

NASA Image and Video Library

1989-11-22

STS033-S-002 (22 Nov 1989) --- The Space Shuttle Discovery heads for Earth orbit on the first post-Challenger nocturnal launch. Liftoff occurred at 7:23:29:989 p.m. (EST), November 22, 1989. This picture shows a side view of Discovery, one of its two solid rocket boosters (SRB) and the external tank. It represents a good example of the "diamond shock" effect, in the plume from the main engine, associated with Shuttle launches. Onboard for the DOD-devoted mission were Astronauts Frederick D. Gregory, John E. Blaha, F. Story Musgrave, Kathryn C. Thornton and Manley L. Carter.

Doors to Discovery[TM]. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2013

2013-01-01

"Doors to Discovery"]TM] is a preschool literacy curriculum that uses eight thematic units of activities to help children build fundamental early literacy skills in oral language, phonological awareness, concepts of print, alphabet knowledge, writing, and comprehension. The eight thematic units cover topics such as nature, friendship,…

Three-Dimensional Cell Cultures in Drug Discovery and Development

PubMed Central

Fang, Ye; Eglen, Richard M.

2017-01-01

The past decades have witnessed significant efforts toward the development of three-dimensional (3D) cell cultures as systems that better mimic in vivo physiology. Today, 3D cell cultures are emerging, not only as a new tool in early drug discovery but also as potential therapeutics to treat disease. In this review, we assess leading 3D cell culture technologies and their impact on drug discovery, including spheroids, organoids, scaffolds, hydrogels, organs-on-chips, and 3D bioprinting. We also discuss the implementation of these technologies in compound identification, screening, and development, ranging from disease modeling to assessment of efficacy and safety profiles. PMID:28520521

Bead-based screening in chemical biology and drug discovery.

PubMed

Komnatnyy, Vitaly V; Nielsen, Thomas E; Qvortrup, Katrine

2018-06-11

High-throughput screening is an important component of the drug discovery process. The screening of libraries containing hundreds of thousands of compounds requires assays amenable to miniaturisation and automization. Combinatorial chemistry holds a unique promise to deliver structurally diverse libraries for early drug discovery. Among the various library forms, the one-bead-one-compound (OBOC) library, where each bead carries many copies of a single compound, holds the greatest potential for the rapid identification of novel hits against emerging drug targets. However, this potential has not yet been fully realized due to a number of technical obstacles. In this feature article, we review the progress that has been made in bead-based library screening and its application to the discovery of bioactive compounds. We identify the key challenges of this approach and highlight key steps needed for making a greater impact in the field.

Recent SPIRITS discoveries of Infrared Transients and Variables with Spitzer/IRAC

NASA Astrophysics Data System (ADS)

Jencson, J. E.; Kasliwal, M. M.; Adams, S.; Cook, D.; Tinyanont, S.; Kwan, S.; Prince, T.; Lau, R. M.; Perley, D.; Masci, F.; Helou, G.; Armus, L.; Surace, J.; Dyk, S. D. Van; Cody, A.; Boyer, M. L.; Bond, H. E.; Monson, A.; Bally, J.; Khan, R.; Levesque, E.; Fox, O.; Williams, R.; Whitelock, P. A.; Mohamed, S.; Gehrz, R. D.; Amodeo, S.; Shenoy, D.; Carlon, R.; Cass, A.; Corgan, D.; Dykhoff, D.; Faella, J.; Gburek, T.; Smith, N.; Cantiello, M.; Langer, N.; Ofek, E.; Johansson, J.; Parthasarathy, M.; Hsiao, E.; Phillips, M.; Morrell, N.; Gonzalez, C.; Contreras, C.

2018-04-01

We report the discoveries of mid-infrared transients/strong variables found in the course of the Spitzer InfraRed Intensive Transients Survey (SPIRITS) using Spitzer Early Release Data (ATel #6644, #7929, #8688, #8940, #9434, #10171, #10172, #10488, #10903).

The minimal SUSY B - L model: from the unification scale to the LHC

DOE PAGES

Ovrut, Burt A.; Purves, Austin; Spinner, Sogee

2015-06-26

Here, this paper introduces a random statistical scan over the high-energy initial parameter space of the minimal SUSY B - L model — denoted as the B - L MSSM. Each initial set of points is renormalization group evolved to the electroweak scale — being subjected, sequentially, to the requirement of radiative B - L and electroweak symmetry breaking, the present experimental lower bounds on the B - L vector boson and sparticle masses, as well as the lightest neutral Higgs mass of ~125 GeV. The subspace of initial parameters that satisfies all such constraints is presented, shown to bemore » robust and to contain a wide range of different configurations of soft supersymmetry breaking masses. The low-energy predictions of each such “valid” point — such as the sparticle mass spectrum and, in particular, the LSP — are computed and then statistically analyzed over the full subspace of valid points. Finally, the amount of fine-tuning required is quantified and compared to the MSSM computed using an identical random scan. The B - L MSSM is shown to generically require less fine-tuninng.« less

First discovery of colobine fossils from the Late Miocene/Early Pliocene in central Myanmar.

PubMed

Takai, Masanaru; Thaung-Htike; Zin-Maung-Maung-Thein; Soe, Aung Naing; Maung, Maung; Tsubamoto, Takehisa; Egi, Naoko; Nishimura, Takeshi D; Nishioka, Yuichiro

2015-07-01

Here we report two kinds of colobine fossils discovered from the latest Miocene/Early Pliocene Irrawaddy sediments of the Chaingzauk area, central Myanmar. A left mandibular corpus fragment preserving M1-3 is named as a new genus and species, Myanmarcolobus yawensis. Isolated upper (M(1)?) and lower (M2) molars are tentatively identified as Colobinae gen. et sp. indet. Although both forms are medium-sized colobines, they are quite different from each other in M2 morphology. The isolated teeth of the latter show typical colobine-type features, so it is difficult to identify their taxonomic position, whereas lower molars of Myanmarcolobus have unique features, such as a trapezoid-shaped long median lingual notch, a deeply concave median buccal cleft, a strongly developed mesiobuccal notch, and rather obliquely running transverse lophids. Compared with fossil and living Eurasian colobine genera, Myanmarcolobus is most similar in lower molar morphology to the Pliocene Dolichopithecus of Europe rather than to any Asian forms. In Dolichopithecus, however, the tooth size is much larger and the median lingual notch is mesiodistally much shorter than that of Myanmarcolobus. The discovery of Myanmarcolobus in central Myanmar is the oldest fossil record in Southeast Asia not only of colobine but also of cercopithecid monkeys and raises many questions regarding the evolutionary history of Asian colobine monkeys. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Joseph Henry’s role in the discovery of electromagnetic induction

NASA Astrophysics Data System (ADS)

Smith, Glenn S.

2017-01-01

The discovery of electromagnetic induction in the early part of the 19th century is one of the greatest scientific achievements of all time, and it has had tremendous technological consequences. The credit for this discovery rightfully goes to the great English experimental physicist Michael Faraday. However, the American physicist Joseph Henry made some observations comparable to Faraday’s at nearly the same time, and for that reason, Faraday and Henry are often considered to be co-discoverers of some aspects of electromagnetic induction. We examine Henry’s early research on electromagnetism, starting from his efforts to improve the electromagnet, which led directly to his investigations of induction. We describe his earliest experiments on both mutual and self-induction, and pay particular attention to the relationship of Henry’s research to that of Faraday. The approach is one in which the experiments are described and then analysed using modern theory and terminology.

Emergence of Chinese drug discovery research: impact of hit and lead identification.

PubMed

Zhou, Caihong; Zhou, Yan; Wang, Jia; Zhu, Yue; Deng, Jiejie; Wang, Ming-Wei

2015-03-01

The identification of hits and the generation of viable leads is an early and yet crucial step in drug discovery. In the West, the main players of drug discovery are pharmaceutical and biotechnology companies, while in China, academic institutions remain central in the field of drug discovery. There has been a tremendous amount of investment from the public as well as private sectors to support infrastructure buildup and expertise consolidation relative to drug discovery and development in the past two decades. A large-scale compound library has been established in China, and a series of high-impact discoveries of lead compounds have been made by integrating information obtained from different technology-based strategies. Natural products are a major source in China's drug discovery efforts. Knowledge has been enhanced via disruptive breakthroughs such as the discovery of Boc5 as a nonpeptidic agonist of glucagon-like peptide 1 receptor (GLP-1R), one of the class B G protein-coupled receptors (GPCRs). Most of the original hit identification and lead generation were carried out by academic institutions, including universities and specialized research institutes. The Chinese pharmaceutical industry is gradually transforming itself from manufacturing low-end generics and active pharmaceutical ingredients to inventing new drugs. © 2014 Society for Laboratory Automation and Screening.

Proteomic profiling of human plasma for cancer biomarker discovery.

PubMed

Huang, Zhao; Ma, Linguang; Huang, Canhua; Li, Qifu; Nice, Edouard C

2017-03-01

Over the past decades, substantial advances have been made in both the early diagnosis and accurate prognosis of many cancers because of the impressive development of novel proteomic strategies. However, it remains difficult to standardize proteomic approaches. In addition, the heterogeneity of proteins in distinct tissues results in incomplete population of the whole proteome, which inevitably limits its clinical practice. As one of the most complex proteomes in the human body, the plasma proteome contains secreted proteins originating from multiple organs and tissues, making it a favorable matrix for comprehensive biomarker discovery. Here, we will discuss the roles of plasma proteome profiling in cancer biomarker discovery and validation, and highlight both the inherent advantages and disadvantages. Although several hurdles lay ahead, further advances in this technology will greatly increase our understanding of cancer biology, reveal new biomarkers and biomarker panels, and open a new avenue for more efficient early diagnosis and surveillance of cancer, leading toward personalized medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Elements of discovery.

PubMed

Toledo-Pereyra, Luis H

2008-01-01

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

Medicinal chemistry inspired fragment-based drug discovery.

PubMed

Lanter, James; Zhang, Xuqing; Sui, Zhihua

2011-01-01

Lead generation can be a very challenging phase of the drug discovery process. The two principal methods for this stage of research are blind screening and rational design. Among the rational or semirational design approaches, fragment-based drug discovery (FBDD) has emerged as a useful tool for the generation of lead structures. It is particularly powerful as a complement to high-throughput screening approaches when the latter failed to yield viable hits for further development. Engagement of medicinal chemists early in the process can accelerate the progression of FBDD efforts by incorporating drug-friendly properties in the earliest stages of the design process. Medium-chain acyl-CoA synthetase 2b and ketohexokinase are chosen as examples to illustrate the importance of close collaboration of medicinal chemists, crystallography, and modeling. Copyright © 2011 Elsevier Inc. All rights reserved.

A Virtual Bioinformatics Knowledge Environment for Early Cancer Detection

NASA Technical Reports Server (NTRS)

Crichton, Daniel; Srivastava, Sudhir; Johnsey, Donald

2003-01-01

Discovery of disease biomarkers for cancer is a leading focus of early detection. The National Cancer Institute created a network of collaborating institutions focused on the discovery and validation of cancer biomarkers called the Early Detection Research Network (EDRN). Informatics plays a key role in enabling a virtual knowledge environment that provides scientists real time access to distributed data sets located at research institutions across the nation. The distributed and heterogeneous nature of the collaboration makes data sharing across institutions very difficult. EDRN has developed a comprehensive informatics effort focused on developing a national infrastructure enabling seamless access, sharing and discovery of science data resources across all EDRN sites. This paper will discuss the EDRN knowledge system architecture, its objectives and its accomplishments.

The dendritic spine story: an intriguing process of discovery.

PubMed

DeFelipe, Javier

2015-01-01

Dendritic spines are key components of a variety of microcircuits and they represent the majority of postsynaptic targets of glutamatergic axon terminals in the brain. The present article will focus on the discovery of dendritic spines, which was possible thanks to the application of the Golgi technique to the study of the nervous system, and will also explore the early interpretation of these elements. This discovery represents an interesting chapter in the history of neuroscience as it shows us that progress in the study of the structure of the nervous system is based not only on the emergence of new techniques but also on our ability to exploit the methods already available and correctly interpret their microscopic images.

Modified parton branching model for multi-particle production in hadronic collisions: Application to SUSY particle branching

NASA Astrophysics Data System (ADS)

Yuanyuan, Zhang

The stochastic branching model of multi-particle productions in high energy collision has theoretical basis in perturbative QCD, and also successfully describes the experimental data for a wide energy range. However, over the years, little attention has been put on the branching model for supersymmetric (SUSY) particles. In this thesis, a stochastic branching model has been built to describe the pure supersymmetric particle jets evolution. This model is a modified two-phase stochastic branching process, or more precisely a two phase Simple Birth Process plus Poisson Process. The general case that the jets contain both ordinary particle jets and supersymmetric particle jets has also been investigated. We get the multiplicity distribution of the general case, which contains a Hypergeometric function in its expression. We apply this new multiplicity distribution to the current experimental data of pp collision at center of mass energy √s = 0.9, 2.36, 7 TeV. The fitting shows the supersymmetric particles haven't participate branching at current collision energy.

Computational drug discovery

PubMed Central

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

2012-01-01

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

Natural product discovery: past, present, and future.

PubMed

Katz, Leonard; Baltz, Richard H

2016-03-01

Microorganisms have provided abundant sources of natural products which have been developed as commercial products for human medicine, animal health, and plant crop protection. In the early years of natural product discovery from microorganisms (The Golden Age), new antibiotics were found with relative ease from low-throughput fermentation and whole cell screening methods. Later, molecular genetic and medicinal chemistry approaches were applied to modify and improve the activities of important chemical scaffolds, and more sophisticated screening methods were directed at target disease states. In the 1990s, the pharmaceutical industry moved to high-throughput screening of synthetic chemical libraries against many potential therapeutic targets, including new targets identified from the human genome sequencing project, largely to the exclusion of natural products, and discovery rates dropped dramatically. Nonetheless, natural products continued to provide key scaffolds for drug development. In the current millennium, it was discovered from genome sequencing that microbes with large genomes have the capacity to produce about ten times as many secondary metabolites as was previously recognized. Indeed, the most gifted actinomycetes have the capacity to produce around 30-50 secondary metabolites. With the precipitous drop in cost for genome sequencing, it is now feasible to sequence thousands of actinomycete genomes to identify the "biosynthetic dark matter" as sources for the discovery of new and novel secondary metabolites. Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.

STS-91 Launch of Discovery from Launch Pad 39-A

NASA Technical Reports Server (NTRS)

1998-01-01

Searing the early evening sky with its near sun-like rocket exhaust, the Space Shuttle Discovery lifts off from Launch Pad 39A at 6:06:24 p.m. EDT June 2 on its way to the Mir space station. On board Discovery are Mission Commander Charles J. Precourt; Pilot Dominic L. Gorie; and Mission Specialists Wendy B. Lawrence, Franklin R. Chang-Diaz, Janet Lynn Kavandi and Valery Victorovitch Ryumin. The nearly 10-day mission will feature the ninth and final Shuttle docking with the Russian space station Mir, the first Mir docking for the Space Shuttle orbiter Discovery, the first on-orbit test of the Alpha Magnetic Spectrometer (AMS), and the first flight of the new Space Shuttle super lightweight external tank. Astronaut Andrew S. W. Thomas will be returning to Earth as a STS-91 crew member after living more than four months aboard Mir.

Fifty years of herbicide research: comparing the discovery of trifluralin and halauxifen-methyl.

PubMed

Epp, Jeffrey B; Schmitzer, Paul R; Crouse, Gary D

2018-01-01

Fifty years separate the commercialization of the herbicides trifluralin and halauxifen-methyl. Despite the vast degree of technological change that occurred over that time frame, some aspects of their discovery stories are remarkably similar. For example, both herbicides were prepared very early in the iterative discovery process and both were developed from known lead compound structures by hypothesis-driven research efforts without the use of in vitro assays or computer-aided molecular design. However, there are aspects of the halauxifen-methyl and trifluralin discovery stories that are substantially different. For example, the chemical technology required for the cost-effective production of halauxifen-methyl simply did not exist just two decades prior to its commercial launch. By contrast, the chemical technology required for the cost-effective production of trifluralin was reported in the chemical literature more than two decades prior to its commercial launch. In addition, changes in regulatory environment since the early 1960s ensured that their respective discovery to commercial launch stories would also differ in substantial ways. Ultimately, the time and cost required to develop and register halauxifen-methyl demanded a global initial business case while the lower registration hurdles that trifluralin cleared enabled a narrow initial business case mainly focused on the USA. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities.

PubMed

Huang, Boshi; Kang, Dongwei; Zhan, Peng; Liu, Xinyong

2015-12-01

The search for additional drugs to treat HIV infection is a continuing effort due to the emergence and spread of HIV strains resistant to nearly all current drugs. The recent literature reveals that fragment-based drug design/discovery (FBDD) has become an effective alternative to conventional high-throughput screening strategies for drug discovery. In this critical review, the authors describe the state of the art in FBDD strategies for the discovery of anti-HIV drug-like compounds. The article focuses on fragment screening techniques, direct fragment-based design and early hit-to-lead progress. Rapid progress in biophysical detection and in silico techniques has greatly aided the application of FBDD to discover candidate agents directed at a variety of anti-HIV targets. Growing evidence suggests that structural insights on key proteins in the HIV life cycle can be applied in the early phase of drug discovery campaigns, providing valuable information on the binding modes and efficiently prompting fragment hit-to-lead progression. The combination of structural insights with improved methodologies for FBDD, including the privileged fragment-based reconstruction approach, fragment hybridization based on crystallographic overlays, fragment growth exploiting dynamic combinatorial chemistry, and high-speed fragment assembly via diversity-oriented synthesis followed by in situ screening, offers the possibility of more efficient and rapid discovery of novel drugs for HIV-1 prevention or treatment. Though the use of FBDD in anti-HIV drug discovery is still in its infancy, it is anticipated that anti-HIV agents developed via fragment-based strategies will be introduced into the clinic in the future.

Water resources and potential effects of ground-water development in Maggie, Marys, and Susie Creek basins, Elko and Eureka counties, Nevada

USGS Publications Warehouse

Plume, R.W.

1995-01-01

The basins of Maggie, Marys, and Susie Creeks in northeastern Nevada are along the Carline trend, an area of large, low-grade gold deposits. Pumping of ground water, mostly for pit dewatering at one of the mines, will reach maximum rates of about 70,000 acre-ft/yr (acre-feet per year) around the year 2000. This pumping is expected to affect ground-water levels, streamflow, and possibly the flow of Carlin spring, which is the water supply for the town of Carlin, Nev. Ground water in the upper Maggie Creek Basin moves from recharge areas in mountain ranges toward the basin axis and discharges as evapotranspiration and as inflow to the stream channel. Ground water in the lower Maggie, Marys, and Susie Creek Basins moves southward from recharge areas in mountain ranges and along the channel of lower Maggie Creek to the discharge area along the Humboldt River. Ground-water underflow between basins is through permeable bedrock of Schroeder Mountain from the upper Maggie Creek Basin to the lower Maggie Creek Basin and through permeable volcanic rocks from lower Maggie Creek to Carlin spring in the Marys Creek Basin. The only source of water to the combined area of the three basins is an estimated 420,000 acre-ft/yr of precipitation. Water leaves as runoff (38,000 acre-ft/yr) and evapotranspiration of soil moisture and ground water (380,000 acre-ft/yr). A small part of annual precipitation (about 25,000 acre-ft/yr) infiltrates the soil zone and becomes ground-water recharge. This ground water eventually is discharged as evapotranspiration (11,000 acre-ft/yr) and as inflow to the Humboldt River channel and nearby springflow (7,000 acre-ft/yr). Total discharge is estimated to be 18,000 acre-ft/yr.

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

PubMed

Shou, Wilson Z; Zhang, Jun

2012-05-01

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

Discovery, Progenitor and Early Evolution of a Stripped Envelope Supernova iPTF13bvn

NASA Astrophysics Data System (ADS)

Cao, Yi; Kasliwal, Mansi M.; Arcavi, Iair; Horesh, Assaf; Hancock, Paul; Valenti, Stefano; Cenko, S. Bradley; Kulkarni, S. R.; Gal-Yam, Avishay; Gorbikov, Evgeny; Ofek, Eran O.; Sand, David; Yaron, Ofer; Graham, Melissa; Silverman, Jeffrey M.; Wheeler, J. Craig; Marion, G. H.; Walker, Emma S.; Mazzali, Paolo; Howell, D. Andrew; Li, K. L.; Kong, A. K. H.; Bloom, Joshua S.; Nugent, Peter E.; Surace, Jason; Masci, Frank; Carpenter, John; Degenaar, Nathalie; Gelino, Christopher R.

2013-09-01

The intermediate Palomar Transient Factory reports our discovery of a young supernova, iPTF13bvn, in the nearby galaxy, NGC 5806 (22.5 Mpc). Our spectral sequence in the optical and infrared suggests a Type Ib classification. We identify a blue progenitor candidate in deep pre-explosion imaging within a 2σ error circle of 80 mas (8.7 pc). The candidate has an MB luminosity of -5.52 ± 0.39 mag and a B - I color of 0.25 ± 0.25 mag. If confirmed by future observations, this would be the first direct detection for a progenitor of a Type Ib. Fitting a power law to the early light curve, we find an extrapolated explosion date around 0.6 days before our first detection. We see no evidence of shock cooling. The pre-explosion detection limits constrain the radius of the progenitor to be smaller than a few solar radii. iPTF13bvn is also detected in centimeter and millimeter wavelengths. Fitting a synchrotron self-absorption model to our radio data, we find a mass-loading parameter of 1.3×1012 g cm-1. Assuming a wind velocity of 103 km s-1, we derive a progenitor mass-loss rate of 3 × 10-5 M ⊙ yr-1. Our observations, taken as a whole, are consistent with a Wolf-Rayet progenitor of the supernova iPTF13bvn.

Natural little hierarchy for SUSY from radiative breaking of the Peccei-Quinn symmetry

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Baer, Howard; Serce, Hasan

2015-01-01

While LHC8 Higgs mass and sparticle search constraints favor a multi-TeV value of soft SUSY breaking terms, electroweak naturalness favors a superpotential Higgsino mass μ ˜100 - 200 GeV : the mismatch results in an apparent little hierarchy characterized by μ ≪msoft (with msoft˜m3 /2 in gravity mediation). It has been suggested that the little hierarchy arises from a mismatch between Peccei-Quinn (PQ) and hidden sector intermediate scales vPQ≪mhidden . We examine the Murayama-Suzuki-Yanagida model of radiatively driven PQ symmetry breaking which not only generates a weak scale value of μ but also produces intermediate scale Majorana masses for right-hand neutrinos. For this model, we show ranges of parameter choices with multi-TeV values of m3 /2 which can easily generate values of μ ˜100 - 200 GeV so that the apparent little hierarchy suggested from data emerges quite naturally. In such a scenario, dark matter would be comprised of an axion plus a Higgsino-like weakly-interacting massive particle admixture where the axion mass and Higgsino masses are linked by the value of the PQ scale. The required light Higgsinos should ultimately be detected at a linear e+e- collider with √{s }>2 m (Higgsino) .

Designing an intuitive web application for drug discovery scientists.

PubMed

Karamanis, Nikiforos; Pignatelli, Miguel; Carvalho-Silva, Denise; Rowland, Francis; Cham, Jennifer A; Dunham, Ian

2018-06-01

We discuss how we designed the Open Targets Platform (www.targetvalidation.org), an intuitive application for bench scientists working in early drug discovery. To meet the needs of our users, we applied lean user experience (UX) design methods: we started engaging with users very early and carried out research, design and evaluation activities within an iterative development process. We also emphasize the collaborative nature of applying lean UX design, which we believe is a foundation for success in this and many other scientific projects. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

pH-Dependent solubility and permeability criteria for provisional biopharmaceutics classification (BCS and BDDCS) in early drug discovery.

PubMed

Varma, Manthena V; Gardner, Iain; Steyn, Stefanus J; Nkansah, Paul; Rotter, Charles J; Whitney-Pickett, Carrie; Zhang, Hui; Di, Li; Cram, Michael; Fenner, Katherine S; El-Kattan, Ayman F

2012-05-07

pH-dependent permeability and solubility criteria that can be used to assign provisional biopharmaceutics class at early stage of the drug discovery process. Additionally, such a classification system will enable discovery scientists to assess the potential limiting factors to oral absorption, as well as help predict the drug disposition mechanisms and potential drug-drug interactions.

Perspectives on bioanalytical mass spectrometry and automation in drug discovery.

PubMed

Janiszewski, John S; Liston, Theodore E; Cole, Mark J

2008-11-01

The use of high speed synthesis technologies has resulted in a steady increase in the number of new chemical entities active in the drug discovery research stream. Large organizations can have thousands of chemical entities in various stages of testing and evaluation across numerous projects on a weekly basis. Qualitative and quantitative measurements made using LC/MS are integrated throughout this process from early stage lead generation through candidate nomination. Nearly all analytical processes and procedures in modern research organizations are automated to some degree. This includes both hardware and software automation. In this review we discuss bioanalytical mass spectrometry and automation as components of the analytical chemistry infrastructure in pharma. Analytical chemists are presented as members of distinct groups with similar skillsets that build automated systems, manage test compounds, assays and reagents, and deliver data to project teams. The ADME-screening process in drug discovery is used as a model to highlight the relationships between analytical tasks in drug discovery. Emerging software and process automation tools are described that can potentially address gaps and link analytical chemistry related tasks. The role of analytical chemists and groups in modern 'industrialized' drug discovery is also discussed.

The dendritic spine story: an intriguing process of discovery

PubMed Central

DeFelipe, Javier

2015-01-01

Dendritic spines are key components of a variety of microcircuits and they represent the majority of postsynaptic targets of glutamatergic axon terminals in the brain. The present article will focus on the discovery of dendritic spines, which was possible thanks to the application of the Golgi technique to the study of the nervous system, and will also explore the early interpretation of these elements. This discovery represents an interesting chapter in the history of neuroscience as it shows us that progress in the study of the structure of the nervous system is based not only on the emergence of new techniques but also on our ability to exploit the methods already available and correctly interpret their microscopic images. PMID:25798090

The evolution of the matrix metalloproteinase inhibitor drug discovery program at abbott laboratories.

PubMed

Wada, Carol K

2004-01-01

Matrix metalloproteinases (MMPs) have been implicated in several pathologies. At Abbott Laboratories, the matrix metalloproteinases inhibitor drug discovery program has focused on the discovery of a potent, selective, orally bioavailable MMP inhibitor for the treatment of cancer. The program evolved from early succinate-based inhibitors to utilizing in-house technology such as SAR by NMR to develop a novel class of biaryl hydroxamate MMP inhibitors. The metabolic instability of the biaryl hydroxamates led to the discovery of a new class of N-formylhydroxylamine (retrohydroxamate) biaryl ethers, exemplified by ABT-770 (16). Toxicity issues with this pre-clinical candidate led to the discovery of another novel class of retrohydroxamate MMP inhibitors, the phenoxyphenyl sulfones such as ABT-518 (19j). ABT-518 is a potent, orally bioavailable, selective inhibitor of MMP-2 and 9 over MMP-1 that has been evaluated in Phase I clinical trials in cancer patients.

Early evolution and ecology of camouflage in insects

PubMed Central

Pérez-de la Fuente, Ricardo; Delclòs, Xavier; Peñalver, Enrique; Speranza, Mariela; Wierzchos, Jacek; Ascaso, Carmen; Engel, Michael S.

2012-01-01

Taxa within diverse lineages select and transport exogenous materials for the purposes of camouflage. This adaptive behavior also occurs in insects, most famously in green lacewing larvae who nestle the trash among setigerous cuticular processes, known as trash-carrying, rendering them nearly undetectable to predators and prey, as well as forming a defensive shield. We report an exceptional discovery of a green lacewing larva in Early Cretaceous amber from Spain with specialized cuticular processes forming a dorsal basket that carry a dense trash packet. The trash packet is composed of trichomes of gleicheniacean ferns, which highlight the presence of wildfires in this early forest ecosystem. This discovery provides direct evidence of an early acquisition of a sophisticated behavioral suite in stasis for over 110 million years and an ancient plant–insect interaction. PMID:23236135

Early evolution and ecology of camouflage in insects.

PubMed

Pérez-de la Fuente, Ricardo; Delclòs, Xavier; Peñalver, Enrique; Speranza, Mariela; Wierzchos, Jacek; Ascaso, Carmen; Engel, Michael S

2012-12-26

Taxa within diverse lineages select and transport exogenous materials for the purposes of camouflage. This adaptive behavior also occurs in insects, most famously in green lacewing larvae who nestle the trash among setigerous cuticular processes, known as trash-carrying, rendering them nearly undetectable to predators and prey, as well as forming a defensive shield. We report an exceptional discovery of a green lacewing larva in Early Cretaceous amber from Spain with specialized cuticular processes forming a dorsal basket that carry a dense trash packet. The trash packet is composed of trichomes of gleicheniacean ferns, which highlight the presence of wildfires in this early forest ecosystem. This discovery provides direct evidence of an early acquisition of a sophisticated behavioral suite in stasis for over 110 million years and an ancient plant-insect interaction.

Network-Based Approaches in Drug Discovery and Early Development

PubMed Central

Harrold, JM; Ramanathan, M; Mager, DE

2015-01-01

Identification of novel targets is a critical first step in the drug discovery and development process. Most diseases such as cancer, metabolic disorders, and neurological disorders are complex, and their pathogenesis involves multiple genetic and environmental factors. Finding a viable drug target–drug combination with high potential for yielding clinical success within the efficacy–toxicity spectrum is extremely challenging. Many examples are now available in which network-based approaches show potential for the identification of novel targets and for the repositioning of established targets. The objective of this article is to highlight network approaches for identifying novel targets with greater chances of gaining approved drugs with maximal efficacy and minimal side effects. Further enhancement of these approaches may emerge from effectively integrating computational systems biology with pharmacodynamic systems analysis. Coupling genomics, proteomics, and metabolomics databases with systems pharmacology modeling may aid in the development of disease-specific networks that can be further used to build confidence in target identification. PMID:24025802

History and utility of zeolite framework-type discovery from a data-science perspective

DOE PAGES

Zimmermann, Nils E. R.; Haranczyk, Maciej

2016-05-02

Mature applications such as fluid catalytic cracking and hydrocracking rely critically on early zeolite structures. With a data-driven approach, we find that the discovery of exceptional zeolite framework types around the new millennium was spurred by exciting new utilization routes. The promising processes have yet not been successfully implemented (“valley of death” effect), mainly because of the lack of thermal stability of the crystals. As a result, this foreshadows limited deployability of recent zeolite discoveries that were achieved by novel crystal synthesis routes.

Compound annotation with real time cellular activity profiles to improve drug discovery.

PubMed

Fang, Ye

2016-01-01

In the past decade, a range of innovative strategies have been developed to improve the productivity of pharmaceutical research and development. In particular, compound annotation, combined with informatics, has provided unprecedented opportunities for drug discovery. In this review, a literature search from 2000 to 2015 was conducted to provide an overview of the compound annotation approaches currently used in drug discovery. Based on this, a framework related to a compound annotation approach using real-time cellular activity profiles for probe, drug, and biology discovery is proposed. Compound annotation with chemical structure, drug-like properties, bioactivities, genome-wide effects, clinical phenotypes, and textural abstracts has received significant attention in early drug discovery. However, these annotations are mostly associated with endpoint results. Advances in assay techniques have made it possible to obtain real-time cellular activity profiles of drug molecules under different phenotypes, so it is possible to generate compound annotation with real-time cellular activity profiles. Combining compound annotation with informatics, such as similarity analysis, presents a good opportunity to improve the rate of discovery of novel drugs and probes, and enhance our understanding of the underlying biology.

Bioinformatics in protein kinases regulatory network and drug discovery.

PubMed

Chen, Qingfeng; Luo, Haiqiong; Zhang, Chengqi; Chen, Yi-Ping Phoebe

2015-04-01

Protein kinases have been implicated in a number of diseases, where kinases participate many aspects that control cell growth, movement and death. The deregulated kinase activities and the knowledge of these disorders are of great clinical interest of drug discovery. The most critical issue is the development of safe and efficient disease diagnosis and treatment for less cost and in less time. It is critical to develop innovative approaches that aim at the root cause of a disease, not just its symptoms. Bioinformatics including genetic, genomic, mathematics and computational technologies, has become the most promising option for effective drug discovery, and has showed its potential in early stage of drug-target identification and target validation. It is essential that these aspects are understood and integrated into new methods used in drug discovery for diseases arisen from deregulated kinase activity. This article reviews bioinformatics techniques for protein kinase data management and analysis, kinase pathways and drug targets and describes their potential application in pharma ceutical industry. Copyright © 2015 Elsevier Inc. All rights reserved.

Discovery Systems

NASA Technical Reports Server (NTRS)

Pell, Barney

2003-01-01

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

14 CFR 406.143 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Discovery. 406.143 Section 406.143... Transportation Adjudications § 406.143 Discovery. (a) Initiation of discovery. Any party may initiate discovery... after a complaint has been filed. (b) Methods of discovery. The following methods of discovery are...

14 CFR 406.143 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Discovery. 406.143 Section 406.143... Transportation Adjudications § 406.143 Discovery. (a) Initiation of discovery. Any party may initiate discovery... after a complaint has been filed. (b) Methods of discovery. The following methods of discovery are...

14 CFR 406.143 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Discovery. 406.143 Section 406.143... Transportation Adjudications § 406.143 Discovery. (a) Initiation of discovery. Any party may initiate discovery... after a complaint has been filed. (b) Methods of discovery. The following methods of discovery are...

14 CFR 406.143 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Discovery. 406.143 Section 406.143... Transportation Adjudications § 406.143 Discovery. (a) Initiation of discovery. Any party may initiate discovery... after a complaint has been filed. (b) Methods of discovery. The following methods of discovery are...

14 CFR 406.143 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

Inversion induced Manihot esculenta stem tubers express key tuberization genes; Mec1, RZF, SuSy1 and PIN2.

PubMed

Bowrin, Valerie; Sutton, Fedora

2016-01-01

Cassava (M. esculenta) gives rise to unique underground stem tubers when stem cuttings are planted in an inverted orientation. The nutritional profile of the stem and root tubers were similar except for protein content which was higher in stem than in root tubers. RT-PCR revealed that several key genes (Mec1, RZF, SuSy1 and PIN2) involved in root tuberization were also expressed in these stem tubers. At five weeks post planting, these genes were expressed in roots and underground stems as in the mature tubers. However at 15 weeks post planting, they were expressed in both root and stem tubers but not in adventitious roots or in the non-tuberized stems. Expression of, the root auxin efflux carrier gene PIN2 in the stem tubers indicate a role for auxin in the stem tuberization process.

Conceptual biology, hypothesis discovery, and text mining: Swanson's legacy.

PubMed

Bekhuis, Tanja

2006-04-03

Innovative biomedical librarians and information specialists who want to expand their roles as expert searchers need to know about profound changes in biology and parallel trends in text mining. In recent years, conceptual biology has emerged as a complement to empirical biology. This is partly in response to the availability of massive digital resources such as the network of databases for molecular biologists at the National Center for Biotechnology Information. Developments in text mining and hypothesis discovery systems based on the early work of Swanson, a mathematician and information scientist, are coincident with the emergence of conceptual biology. Very little has been written to introduce biomedical digital librarians to these new trends. In this paper, background for data and text mining, as well as for knowledge discovery in databases (KDD) and in text (KDT) is presented, then a brief review of Swanson's ideas, followed by a discussion of recent approaches to hypothesis discovery and testing. 'Testing' in the context of text mining involves partially automated methods for finding evidence in the literature to support hypothetical relationships. Concluding remarks follow regarding (a) the limits of current strategies for evaluation of hypothesis discovery systems and (b) the role of literature-based discovery in concert with empirical research. Report of an informatics-driven literature review for biomarkers of systemic lupus erythematosus is mentioned. Swanson's vision of the hidden value in the literature of science and, by extension, in biomedical digital databases, is still remarkably generative for information scientists, biologists, and physicians.

Discovery lands at KSC after completing mission STS-105

NASA Technical Reports Server (NTRS)

2001-01-01

KENNEDY SPACE CENTER, Fla. With its drag chute trailing behind, orbiter Discovery and its crew land on KSC's Shuttle Landing Facility runway 15. Main gear touchdown was at 2:22:58 p.m. EDT; wheel stop, at 2:24:06 p.m. EDT. The 11-day, 21-hour, 12-minute STS-105 mission accomplished the goals set for the 11th flight to the International Space Station: swapout of the resident Station crew; delivery of equipment, supplies and scientific experiments; and installation of the Early Ammonia Servicer and heater cables for the S0 truss on the Station. Discovery traveled 4.3 million miles on its 30th flight into space, the 106th mission of the Space Shuttle program. The landing was the first of five in 2001 to occur in daylight at KSC.

Discovery lands at KSC after completing mission STS-105

NASA Technical Reports Server (NTRS)

2001-01-01

KENNEDY SPACE CENTER, Fla. Orbiter Discovery and its crew land on KSC's Shuttle Landing Facility runway 15. Main gear touchdown was at 2:22:58 p.m. EDT; wheel stop, at 2:24:06 p.m. EDT. The 11-day, 21-hour, 12-minute STS-105 mission accomplished the goals set for the 11th flight to the International Space Station: swapout of the resident Station crew; delivery of equipment, supplies and scientific experiments; and installation of the Early Ammonia Servicer and heater cables for the S0 truss on the Station. Discovery traveled 4.3 million miles on its 30th flight into space, the 106th mission of the Space Shuttle program. The landing was the first of five in 2001 to occur in daylight at KSC.

Discovery lands at KSC after completing mission STS-105

NASA Technical Reports Server (NTRS)

2001-01-01

KENNEDY SPACE CENTER, Fla. A great blue heron flies along with orbiter Discovery as it lands on KSC's Shuttle Landing Facility runway 15. Main gear touchdown was at 2:22:58 p.m. EDT; wheel stop, at 2:24:06 p.m. EDT. The 11-day, 21-hour, 12-minute STS-105 mission accomplished the goals set for the 11th flight to the International Space Station: swapout of the resident Station crew; delivery of equipment, supplies and scientific experiments; and installation of the Early Ammonia Servicer and heater cables for the S0 truss on the Station. Discovery traveled 4.3 million miles on its 30th flight into space, the 106th mission of the Space Shuttle program. The landing was the first of five in 2001 to occur in daylight at KSC.

From machine learning to deep learning: progress in machine intelligence for rational drug discovery.

PubMed

Zhang, Lu; Tan, Jianjun; Han, Dan; Zhu, Hao

2017-11-01

Machine intelligence, which is normally presented as artificial intelligence, refers to the intelligence exhibited by computers. In the history of rational drug discovery, various machine intelligence approaches have been applied to guide traditional experiments, which are expensive and time-consuming. Over the past several decades, machine-learning tools, such as quantitative structure-activity relationship (QSAR) modeling, were developed that can identify potential biological active molecules from millions of candidate compounds quickly and cheaply. However, when drug discovery moved into the era of 'big' data, machine learning approaches evolved into deep learning approaches, which are a more powerful and efficient way to deal with the massive amounts of data generated from modern drug discovery approaches. Here, we summarize the history of machine learning and provide insight into recently developed deep learning approaches and their applications in rational drug discovery. We suggest that this evolution of machine intelligence now provides a guide for early-stage drug design and discovery in the current big data era. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detecting kinematic boundary surfaces in phase space: particle mass measurements in SUSY-like events

DOE PAGES

Debnath, Dipsikha; Gainer, James S.; Kilic, Can; ...

2017-06-19

We critically examine the classic endpoint method for particle mass determination, focusing on difficult corners of parameter space, where some of the measurements are not independent, while others are adversely affected by the experimental resolution. In such scenarios, mass differences can be measured relatively well, but the overall mass scale remains poorly constrained. Using the example of the standard SUSY decay chain q ~→χ ~ 0 2→ℓ ~→χ ~ 0 1 , we demonstrate that sensitivity to the remaining mass scale parameter can be recovered by measuring the two-dimensional kinematical boundary in the relevant three-dimensional phase space of invariant massesmore » squared. We develop an algorithm for detecting this boundary, which uses the geometric properties of the Voronoi tessellation of the data, and in particular, the relative standard deviation (RSD) of the volumes of the neighbors for each Voronoi cell in the tessellation. We propose a new observable, Σ¯ , which is the average RSD per unit area, calculated over the hypothesized boundary. We show that the location of the Σ¯ maximum correlates very well with the true values of the new particle masses. Our approach represents the natural extension of the one-dimensional kinematic endpoint method to the relevant three dimensions of invariant mass phase space.« less

Detecting kinematic boundary surfaces in phase space: particle mass measurements in SUSY-like events

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

Debnath, Dipsikha; Gainer, James S.; Kilic, Can

We critically examine the classic endpoint method for particle mass determination, focusing on difficult corners of parameter space, where some of the measurements are not independent, while others are adversely affected by the experimental resolution. In such scenarios, mass differences can be measured relatively well, but the overall mass scale remains poorly constrained. Using the example of the standard SUSY decay chain q ~→χ ~ 0 2→ℓ ~→χ ~ 0 1 , we demonstrate that sensitivity to the remaining mass scale parameter can be recovered by measuring the two-dimensional kinematical boundary in the relevant three-dimensional phase space of invariant massesmore » squared. We develop an algorithm for detecting this boundary, which uses the geometric properties of the Voronoi tessellation of the data, and in particular, the relative standard deviation (RSD) of the volumes of the neighbors for each Voronoi cell in the tessellation. We propose a new observable, Σ¯ , which is the average RSD per unit area, calculated over the hypothesized boundary. We show that the location of the Σ¯ maximum correlates very well with the true values of the new particle masses. Our approach represents the natural extension of the one-dimensional kinematic endpoint method to the relevant three dimensions of invariant mass phase space.« less

Detecting kinematic boundary surfaces in phase space: particle mass measurements in SUSY-like events

NASA Astrophysics Data System (ADS)

Debnath, Dipsikha; Gainer, James S.; Kilic, Can; Kim, Doojin; Matchev, Konstantin T.; Yang, Yuan-Pao

2017-06-01

We critically examine the classic endpoint method for particle mass determination, focusing on difficult corners of parameter space, where some of the measurements are not independent, while others are adversely affected by the experimental resolution. In such scenarios, mass differences can be measured relatively well, but the overall mass scale remains poorly constrained. Using the example of the standard SUSY decay chain \\tilde{q}\\to {\\tilde{χ}}_2^0\\to \\tilde{ℓ}\\to {\\tilde{χ}}_1^0 , we demonstrate that sensitivity to the remaining mass scale parameter can be recovered by measuring the two-dimensional kinematical boundary in the relevant three-dimensional phase space of invariant masses squared. We develop an algorithm for detecting this boundary, which uses the geometric properties of the Voronoi tessellation of the data, and in particular, the relative standard deviation (RSD) of the volumes of the neighbors for each Voronoi cell in the tessellation. We propose a new observable, \\overline{Σ} , which is the average RSD per unit area, calculated over the hypothesized boundary. We show that the location of the \\overline{Σ} maximum correlates very well with the true values of the new particle masses. Our approach represents the natural extension of the one-dimensional kinematic endpoint method to the relevant three dimensions of invariant mass phase space.

Intersecting branes, Higgs sector, and chirality from N = 4 SYM with soft SUSY breaking

NASA Astrophysics Data System (ADS)

Sperling, Marcus; Steinacker, Harold C.

2018-04-01

We consider SU( N ) N = 4 super Yang-Mills with cubic and quadratic soft SUSY breaking potential, such that the global SU(4) R is broken to SU(3) or further. As shown recently, this set-up supports a rich set of non-trivial vacua with the geometry of self-intersecting SU(3) branes in 6 extra dimensions. The zero modes on these branes can be interpreted as 3 generations of bosonic and chiral fermionic strings connecting the branes at their intersections. Here, we uncover a large class of exact solutions consisting of branes connected by Higgs condensates, leading to Yukawa couplings between the chiral fermionic zero modes. Under certain decoupling conditions, the backreaction of the Higgs on the branes vanishes exactly. The resulting physics is that of a spontaneously broken chiral gauge theory on branes with fluxes. In particular, we identify combined brane plus Higgs configurations which lead to gauge fields that couple to chiral fermions at low energy. This turns out to be quite close to the Standard Model and its constructions via branes in string theory. As a by-product, we construct a G 2-brane solution corresponding to a squashed fuzzy coadjoint orbit of G 2.

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

PubMed

Scerri, Eric

2015-03-13

The article examines the question of priority and simultaneous discovery in the context of the discovery of the periodic system. It is argued that rather than being anomalous, simultaneous discovery is the rule. Moreover, I argue that the discovery of the periodic system by at least six authors in over a period of 7 years represents one of the best examples of a multiple discovery. This notion is supported by a new view of the evolutionary development of science through a mechanism that is dubbed Sci-Gaia by analogy with Lovelock's Gaia hypothesis. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

"Eureka, Eureka!" Discoveries in Science

ERIC Educational Resources Information Center

Agarwal, Pankaj

2011-01-01

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

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

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

39 CFR 952.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

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

39 CFR 952.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

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

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

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

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

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

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

39 CFR 952.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

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

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

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

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

30 CFR 44.24 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-07-01

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

19 CFR 356.20 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

Chemical Discovery

ERIC Educational Resources Information Center

Brown, Herbert C.

1974-01-01

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

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

22 CFR 224.21 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

Strategies for bringing drug delivery tools into discovery.

PubMed

Kwong, Elizabeth; Higgins, John; Templeton, Allen C

2011-06-30

The past decade has yielded a significant body of literature discussing approaches for development and discovery collaboration in the pharmaceutical industry. As a result, collaborations between discovery groups and development scientists have increased considerably. The productivity of pharma companies to deliver new drugs to the market, however, has not increased and development costs continue to rise. Inability to predict clinical and toxicological response underlies the high attrition rate of leads at every step of drug development. A partial solution to this high attrition rate could be provided by better preclinical pharmacokinetics measurements that inform PD response based on key pathways that drive disease progression and therapeutic response. A critical link between these key pharmacology, pharmacokinetics and toxicology studies is the formulation. The challenges in pre-clinical formulation development include limited availability of compounds, rapid turn-around requirements and the frequent un-optimized physical properties of the lead compounds. Despite these challenges, this paper illustrates some successes resulting from close collaboration between formulation scientists and discovery teams. This close collaboration has resulted in development of formulations that meet biopharmaceutical needs from early stage preclinical in vivo model development through toxicity testing and development risk assessment of pre-clinical drug candidates. Published by Elsevier B.V.

Perfect launch for Space Shuttle Discovery on mission STS-105

NASA Technical Reports Server (NTRS)

2001-01-01

KENNEDY SPACE CENTER, Fla. -- Smoke billows out from Launch Pad 39A as Space Shuttle Discovery soars into the blue sky on mission STS-105 to the International Space Station. Liftoff occurred at 5:10:14 p.m. EDT on this second launch attempt. Launch countdown activities for the 12-day mission were called off Aug. 9 during the T-9 minute hold due to the high potential for lightning, a thick cloud cover and the potential for showers. Besides the Shuttle crew of four, Discovery carries the Expedition Three crew who will replace Expedition Two on the International Space Station. The mission includes the third flight of an Italian-built Multi-Purpose Logistics Module delivering additional scientific racks, equipment and supplies for the Space Station, and two spacewalks. Part of the payload is the Early Ammonia Servicer (EAS) tank, which will be attached to the Station during the spacewalks. The EAS contains spare ammonia for the Station'''s cooling system. The three-member Expedition Two crew will be returning to Earth aboard Discovery after a five-month stay on the Station.

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

37 CFR 42.224 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

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

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

5 CFR 185.122 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

37 CFR 42.224 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

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

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

5 CFR 185.122 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

5 CFR 185.122 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

5 CFR 185.122 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

15 CFR 25.21 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

19 CFR 207.109 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

A look at ligand binding thermodynamics in drug discovery.

PubMed

Claveria-Gimeno, Rafael; Vega, Sonia; Abian, Olga; Velazquez-Campoy, Adrian

2017-04-01

Drug discovery is a challenging endeavor requiring the interplay of many different research areas. Gathering information on ligand binding thermodynamics may help considerably in reducing the risk within a high uncertainty scenario, allowing early rejection of flawed compounds and pushing forward optimal candidates. In particular, the free energy, the enthalpy, and the entropy of binding provide fundamental information on the intermolecular forces driving such interaction. Areas covered: The authors review the current status and recent developments in the application of ligand binding thermodynamics in drug discovery. The thermodynamic binding profile (Gibbs energy, enthalpy, and entropy of binding) can be used for lead selection and optimization (binding enthalpy, selectivity, and adaptability). Expert opinion: Binding thermodynamics provides fundamental information on the forces driving the formation of the drug-target complex. It has been widely accepted that binding thermodynamics may be used as a decision criterion along the ligand optimization process in drug discovery and development. In particular, the binding enthalpy may be used as a guide when selecting and optimizing compounds over a set of potential candidates. However, this has been recently called into question by arguing certain difficulties and in the light of certain experimental examples.

Simulating the drug discovery pipeline: a Monte Carlo approach

PubMed Central

2012-01-01

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

High Throughput Screening for Anti–Trypanosoma cruzi Drug Discovery

PubMed Central

Alonso-Padilla, Julio; Rodríguez, Ana

2014-01-01

The discovery of new therapeutic options against Trypanosoma cruzi, the causative agent of Chagas disease, stands as a fundamental need. Currently, there are only two drugs available to treat this neglected disease, which represents a major public health problem in Latin America. Both available therapies, benznidazole and nifurtimox, have significant toxic side effects and their efficacy against the life-threatening symptomatic chronic stage of the disease is variable. Thus, there is an urgent need for new, improved anti–T. cruzi drugs. With the objective to reliably accelerate the drug discovery process against Chagas disease, several advances have been made in the last few years. Availability of engineered reporter gene expressing parasites triggered the development of phenotypic in vitro assays suitable for high throughput screening (HTS) as well as the establishment of new in vivo protocols that allow faster experimental outcomes. Recently, automated high content microscopy approaches have also been used to identify new parasitic inhibitors. These in vitro and in vivo early drug discovery approaches, which hopefully will contribute to bring better anti–T. cruzi drug entities in the near future, are reviewed here. PMID:25474364

High throughput screening for anti-Trypanosoma cruzi drug discovery.

PubMed

Alonso-Padilla, Julio; Rodríguez, Ana

2014-12-01

The discovery of new therapeutic options against Trypanosoma cruzi, the causative agent of Chagas disease, stands as a fundamental need. Currently, there are only two drugs available to treat this neglected disease, which represents a major public health problem in Latin America. Both available therapies, benznidazole and nifurtimox, have significant toxic side effects and their efficacy against the life-threatening symptomatic chronic stage of the disease is variable. Thus, there is an urgent need for new, improved anti-T. cruzi drugs. With the objective to reliably accelerate the drug discovery process against Chagas disease, several advances have been made in the last few years. Availability of engineered reporter gene expressing parasites triggered the development of phenotypic in vitro assays suitable for high throughput screening (HTS) as well as the establishment of new in vivo protocols that allow faster experimental outcomes. Recently, automated high content microscopy approaches have also been used to identify new parasitic inhibitors. These in vitro and in vivo early drug discovery approaches, which hopefully will contribute to bring better anti-T. cruzi drug entities in the near future, are reviewed here.

Long-term trends in oil and gas discovery rates in lower 48 United States

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

Woods, T.J.

1985-09-01

The Gas Research Institute (GRI), in association with Energy and Environmental Analysis, Inc. (EEA), has developed a data base characterizing the discovered oil and gas fields in the lower 48 United States. The number of fields in this data base reported to have been discovered since 1947 substantially exceeds the count presented in the AAPG survey of new-field discoveries since 1947. The greatest relative difference between the field counts is for fields larger than 10 million bbl of oil equivalent (BOE) (AAPG Class C fields or larger). Two factors contribute to the difference in reported discoveries by field size. First,more » the AAPG survey does not capture all new-field discoveries, particularly in the offshore. Second, the AAPG survey does not update field sizes past 6 years after the field discovery date. Because of reserve appreciation to discovered fields, discovery-trend data based on field-size data should be used with caution, particularly when field-size estimates have not been updated for a substantial period of time. Based on the GRI/EEA data base, the major decline in the discovery rates of large, new oil and gas fields in the lower 48 United States appears to have ended by the early 1960s. Since then, discovery rates seem to have improved. Thus, the outlook for future discoveries of large fields may be much better than previously believed.« less

Discovery lands at KSC after completing mission STS-105

NASA Technical Reports Server (NTRS)

2001-01-01

KENNEDY SPACE CENTER, Fla. Orbiter Discovery and its crew land on KSC's Shuttle Landing Facility runway 15, creating a cloud of smoke as its wheels touch the concrete. Main gear touchdown was at 2:22:58 p.m. EDT; wheel stop, at 2:24:06 p.m. EDT. The 11-day, 21-hour, 12-minute STS-105 mission accomplished the goals set for the 11th flight to the International Space Station: swapout of the resident Station crew; delivery of equipment, supplies and scientific experiments; and installation of the Early Ammonia Servicer and heater cables for the S0 truss on the Station. Discovery traveled 4.3 million miles on its 30th flight into space, the 106th mission of the Space Shuttle program. The landing was the first of five in 2001 to occur in daylight at KSC.

Discovery lands at KSC after completing mission STS-105

NASA Technical Reports Server (NTRS)

2001-01-01

KENNEDY SPACE CENTER, Fla. With its drag chute just beginning to open, orbiter Discovery and its crew land on KSC's Shuttle Landing Facility runway 15. Main gear touchdown was at 2:22:58 p.m. EDT; wheel stop, at 2:24:06 p.m. EDT. The 11-day, 21-hour, 12-minute STS-105 mission accomplished the goals set for the 11th flight to the International Space Station: swapout of the resident Station crew; delivery of equipment, supplies and scientific experiments; and installation of the Early Ammonia Servicer and heater cables for the S0 truss on the Station. Discovery traveled 4.3 million miles on its 30th flight into space, the 106th mission of the Space Shuttle program. The landing was the first of five in 2001 to occur in daylight at KSC.

39 CFR 963.14 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

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

39 CFR 963.14 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

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

39 CFR 963.14 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

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

39 CFR 963.14 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

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

39 CFR 963.14 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Discovery. 963.14 Section 963.14 Postal Service... PANDERING ADVERTISEMENTS STATUTE, 39 U.S.C. 3008 § 963.14 Discovery. Discovery is to be conducted on a... such discovery as he or she deems reasonable and necessary. Discovery may include one or more of the...

The discovery and early understanding of leukemia.

PubMed

Kampen, Kim R

2012-01-01

The early history of leukemia reaches back 200 years. In 1811, Peter Cullen defined a case of splenitis acutus with unexplainable milky blood. Alfred Velpeau defined the leukemia associated symptoms, and observed pus in the blood vessels (1825). Alfred Donné detected a maturation arrest of the white blood cells (1844). John Bennett named the disease leucocythemia, based on the microscopic accumulation of purulent leucocytes (1845). That same year, Rudolf Virchow defined a reversed white and red blood cell balance. He introduced the disease as leukämie in 1847. Henry Fuller performed the first microscopic diagnose of a leukemic patient during life (1846). This gradual process brought us towards our current understanding of this complex disease. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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

HOLDEN,N.E.

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

The discovery and early structural studies of arachidonic acid

PubMed Central

Martin, Sarah A.; Brash, Alan R.; Murphy, Robert C.

2016-01-01

Arachidonic acid and esterified arachidonate are ubiquitous components of every mammalian cell. This polyunsaturated fatty acid serves very important biochemical roles, including being the direct precursor of bioactive lipid mediators such as prostaglandin and leukotrienes. This 20 carbon fatty acid with four double bonds was first isolated and identified from mammalian tissues in 1909 by Percival Hartley. This was accomplished prior to the advent of chromatography or any spectroscopic methodology (MS, infrared, UV, or NMR). The name, arachidonic, was suggested in 1913 based on its relationship to the well-known arachidic acid (C20:0). It took until 1940 before the positions of the four double bonds were defined at 5,8,11,14 of the 20-carbon chain. Total synthesis was reported in 1961 and, finally, the configuration of the double bonds was confirmed as all-cis-5,8,11,14. By the 1930s, the relationship of arachidonic acid within the family of essential fatty acids helped cue an understanding of its structure and the biosynthetic pathway. Herein, we review the findings leading up to the discovery of arachidonic acid and the progress toward its complete structural elucidation. PMID:27142391

The minimal SUSY B - L model: simultaneous Wilson lines and string thresholds

DOE PAGES

Deen, Rehan; Ovrut, Burt A.; Purves, Austin

2016-07-08

In previous work, we presented a statistical scan over the soft supersymmetry breaking parameters of the minimal SUSY B - L model. For specificity of calculation, unification of the gauge parameters was enforced by allowing the two Z 3×Z 3 Wilson lines to have mass scales separated by approximately an order of magnitude. This introduced an additional “left-right” sector below the unification scale. In this paper, for three important reasons, we modify our previous analysis by demanding that the mass scales of the two Wilson lines be simultaneous and equal to an “average unification” mass U >. The present analysismore » is 1) more “natural” than the previous calculations, which were only valid in a very specific region of the Calabi-Yau moduli space, 2) the theory is conceptually simpler in that the left-right sector has been removed and 3) in the present analysis the lack of gauge unification is due to threshold effects — particularly heavy string thresholds, which we calculate statistically in detail. As in our previous work, the theory is renormalization group evolved from U > to the electroweak scale — being subjected, sequentially, to the requirement of radiative B - L and electroweak symmetry breaking, the present experimental lower bounds on the B - L vector boson and sparticle masses, as well as the lightest neutral Higgs mass of ~125 GeV. The subspace of soft supersymmetry breaking masses that satisfies all such constraints is presented and shown to be substantial.« less

Moments of discovery.

PubMed

Berg, Paul

2008-01-01

Devoted teachers and mentors during early childhood and adolescence nurtured my ambition to become a scientist, but it was not until I actually began doing experiments in college and graduate school that I was confident about that choice and of making it a reality. During my postdoctoral experiences and thereafter, I made several significant advances, most notably the discovery of the then novel acyl- and aminoacyl adenylates: the former as intermediates in fatty acyl coenzyme A (CoA) formation and the latter as precursors to aminoacyl tRNAs. In the early 1970s, my research changed from a focus on transcription and translation in Escherichia coli to the molecular genetics of mammalian cells. To that end, my laboratory developed a method for creating recombinant DNAs that led us and others, over the next two decades, to create increasingly sophisticated ways for introducing "foreign" DNAs into cultured mammalian cells and to target modifications of specific chromosomal loci. Circumstances surrounding that work drew me into the public policy debates regarding recombinant DNA practices. As an outgrowth of my commitment to teaching, I co-authored several textbooks on molecular genetics and a biography of George Beadle. The colleagues, students, and wealth of associates with whom I interacted have made being a scientist far richer than I can have imagined.

Oncology drug discovery: planning a turnaround.

PubMed

Toniatti, Carlo; Jones, Philip; Graham, Hilary; Pagliara, Bruno; Draetta, Giulio

2014-04-01

We have made remarkable progress in our understanding of the pathophysiology of cancer. This improved understanding has resulted in increasingly effective targeted therapies that are better tolerated than conventional cytotoxic agents and even curative in some patients. Unfortunately, the success rate of drug approval has been limited, and therapeutic improvements have been marginal, with too few exceptions. In this article, we review the current approach to oncology drug discovery and development, identify areas in need of improvement, and propose strategies to improve patient outcomes. We also suggest future directions that may improve the quality of preclinical and early clinical drug evaluation, which could lead to higher approval rates of anticancer drugs.

Discovery of a new X-ray transient in the globular cluster Liller 1

NASA Astrophysics Data System (ADS)

Homan, Jeroen; van den Berg, Maureen; Heinke, Craig; Pooley, David; Degenaar, Nathalie; van den Eijnden, Jakob; Bahramian, Arash; Gendreau, Keith; Arzoumanian, Zaven

2018-05-01

We report on the discovery of a new X-ray transient in the globular cluster Liller 1 with Chandra. Swift/XRT monitoring observations of the globular cluster Liller 1 in early April 2018 revealed low-level activity (around 0.1 ct/s) in the core of the cluster.

Post-LHC7 fine-tuning in the minimal supergravity/CMSSM model with a 125 GeV Higgs boson

NASA Astrophysics Data System (ADS)

Baer, Howard; Barger, Vernon; Huang, Peisi; Mickelson, Dan; Mustafayev, Azar; Tata, Xerxes

2013-02-01

The recent discovery of a 125 GeV Higgs-like resonance at LHC, coupled with the lack of evidence for weak scale supersymmetry (SUSY), has severely constrained SUSY models such as minimal supergravity (mSUGRA)/CMSSM. As LHC probes deeper into SUSY model parameter space, the little hierarchy problem—how to reconcile the Z and Higgs boson mass scale with the scale of SUSY breaking—will become increasingly exacerbated unless a sparticle signal is found. We evaluate two different measures of fine-tuning in the mSUGRA/CMSSM model. The more stringent of these, ΔHS, includes effects that arise from the high-scale origin of the mSUGRA parameters while the second measure, ΔEW, is determined only by weak scale parameters: hence, it is universal to any model with the same particle spectrum and couplings. Our results incorporate the latest constraints from LHC7 sparticle searches, LHCb limits from Bs→μ+μ- and also require a light Higgs scalar with mh˜123-127GeV. We present fine-tuning contours in the m0 vs m1/2 plane for several sets of A0 and tan⁡β values. We also present results for ΔHS and ΔEW from a scan over the entire viable model parameter space. We find a ΔHS≳103, or at best 0.1%, fine-tuning. For the less stringent electroweak fine-tuning, we find ΔEW≳102, or at best 1%, fine-tuning. Two benchmark points are presented that have the lowest values of ΔHS and ΔEW. Our results provide a quantitative measure for ascertaining whether or not the remaining mSUGRA/CMSSM model parameter space is excessively fine-tuned and so could provide impetus for considering alternative SUSY models.

STS-82 Discovery Launch

NASA Technical Reports Server (NTRS)

1997-01-01

The Space Shuttle Discovery cuts a bright swath through the early-morning darkness as it lifts off from Launch Pad 39A on a scheduled 10-day flight to service the Hubble Space Telescope (HST). Liftoff of Mission STS-82 occurred on-time at 3:55:17 a.m. EST, Feb. 11, 1997. Leading the veteran crew is Mission Commander Kenneth D. Bowersox. Scott J. 'Doc' Horowitz is the pilot. Mark C. Lee is the payload commander. Rounding out the seven-member crew are Mission Specialists Steven L. Smith, Gregory J. Harbaugh, Joseph R. 'Joe' Tanner and Steven A. Hawley. Four of the astronauts will be divided into two teams to perform the scheduled four back-to-back extravehicular activities (EVAs) or spacewalks. Lee and Smith will team up for EVAs 1 and 3 on flight days 4 and 6; Harbaugh and Tanner will perform EVAs 2 and 4 on flight days 5 and 7. Among the tasks will be to replace two outdated scientific instruments with two new instruments the Space Telescope Imaging Spectrograph (STIS) and the Near Infrared Camera and Multi-Object Spectrometer (NICMOS). This is the second servicing mission for HST, which was originally deployed in 1990 and designed to be serviced on-orbit about every three years. Hubble was first serviced in 1993. STS-82 is the second of eight planned flights in 1997. It is the 22nd flight of Discovery and the 82nd Shuttle mission.

First diatomyid rodent from the Early Miocene of Arabia

NASA Astrophysics Data System (ADS)

López-Antoñanzas, Raquel

2011-02-01

The Asian family Diatomyidae is known from the Early Oligocene to the present. Among living rodents, this group comprises only the recently discovered Laonastes aenigmamus from Laos. Fossil diatomyids are known from only a few sites, in which they are often rare. The discovery of Pierremus explorator gen. nov. sp. nov. in the Lower Miocene of As-Sarrar (Saudi Arabia) raises to ten the number of extinct diatomyid species recognized. Pierremus explorator is the first record of a diatomyid from the Afro-Arabian plate. This discovery provides evidence that, together with other rodents (ctenodactylids, zapodids…), the diatomyids took advantage of the corridor that was established between Afro-Arabia and Eurasia in Early Miocene times.

Early Homo and the role of the genus in paleoanthropology.

PubMed

Villmoare, Brian

2018-01-01

The history of the discovery of early fossils attributed to the genus Homo has been contentious, with scholars disagreeing over the generic assignment of fossils proposed as members of our genus. In this manuscript I review the history of discovery and debate over early Homo and evaluate the various taxonomic hypotheses for the genus. To get a sense of how hominin taxonomy compares to taxonomic practice outside paleoanthropology, I compare the diversity of Homo to genera in other vertebrate clades. Finally, I propose a taxonomic model that hews closely to current models for hominin phylogeny and is consistent with taxonomic practice across evolutionary biology. © 2018 American Association of Physical Anthropologists.

Solving the muon g -2 anomaly in deflected anomaly mediated SUSY breaking with messenger-matter interactions

NASA Astrophysics Data System (ADS)

Wang, Fei; Wang, Wenyu; Yang, Jin Min

2017-10-01

We propose to introduce general messenger-matter interactions in the deflected anomaly mediated supersymmetry (SUSY) breaking (AMSB) scenario to explain the gμ-2 anomaly. Scenarios with complete or incomplete grand unified theory (GUT) multiplet messengers are discussed, respectively. The introduction of incomplete GUT mulitiplets can be advantageous in various aspects. We found that the gμ-2 anomaly can be solved in both scenarios under current constraints including the gluino mass bounds, while the scenarios with incomplete GUT representation messengers are more favored by the gμ-2 data. We also found that the gluino is upper bounded by about 2.5 TeV (2.0 TeV) in scenario A and 3.0 TeV (2.7 TeV) in scenario B if the generalized deflected AMSB scenarios are used to fully account for the gμ-2 anomaly at 3 σ (2 σ ) level. Such a gluino should be accessible in the future LHC searches. Dark matter (DM) constraints, including DM relic density and direct detection bounds, favor scenario B with incomplete GUT multiplets. Much of the allowed parameter space for scenario B could be covered by the future DM direct detection experiments.

37 CFR 11.52 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 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...

37 CFR 11.52 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 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...

19 CFR 354.10 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 3 2014-04-01 2014-04-01 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...

19 CFR 354.10 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 3 2011-04-01 2011-04-01 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.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 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.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 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...

36 CFR 1150.63 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Discovery. 1150.63 Section... PRACTICE AND PROCEDURES FOR COMPLIANCE HEARINGS Prehearing Conferences and Discovery § 1150.63 Discovery. (a) Parties are encouraged to engage in voluntary discovery procedures. For good cause shown under...

36 CFR 1150.63 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Discovery. 1150.63 Section... PRACTICE AND PROCEDURES FOR COMPLIANCE HEARINGS Prehearing Conferences and Discovery § 1150.63 Discovery. (a) Parties are encouraged to engage in voluntary discovery procedures. For good cause shown under...

19 CFR 354.10 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 3 2013-04-01 2013-04-01 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...

37 CFR 11.52 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 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...

19 CFR 354.10 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 3 2012-04-01 2012-04-01 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...

37 CFR 11.52 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

36 CFR 1150.63 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-07-01

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

19 CFR 354.10 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

28 CFR 76.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 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...

14 CFR 16.213 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 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...

14 CFR 16.213 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 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...

14 CFR 16.213 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 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.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 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...

14 CFR 16.213 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 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.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 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...

28 CFR 76.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 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...

28 CFR 76.21 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

14 CFR 16.213 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

Discovery lands at KSC after completing mission STS-105

NASA Technical Reports Server (NTRS)

2001-01-01

KENNEDY SPACE CENTER, Fla. With its drag chute trailing behind, orbiter Discovery and its crew land on KSC's Shuttle Landing Facility runway 15. The 525-foot-tall Vehicle Assembly Building can be seen in the background. Main gear touchdown was at 2:22:58 p.m. EDT; wheel stop, at 2:24:06 p.m. EDT. The 11-day, 21-hour, 12-minute STS-105 mission accomplished the goals set for the 11th flight to the International Space Station: swapout of the resident Station crew; delivery of equipment, supplies and scientific experiments; and installation of the Early Ammonia Servicer and heater cables for the S0 truss on the Station. Discovery traveled 4.3 million miles on its 30th flight into space, the 106th mission of the Space Shuttle program. The landing was the first of five in 2001 to occur in daylight at KSC.

29 CFR 1955.32 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 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...

49 CFR 1503.633 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 9 2012-10-01 2012-10-01 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...

24 CFR 26.42 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 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 1503.633 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 9 2014-10-01 2014-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or approval of the ALJ, at...

14 CFR 1264.120 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 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...

40 CFR 27.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 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...

24 CFR 26.42 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

29 CFR 1955.32 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 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...

24 CFR 26.42 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 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 604.38 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 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...

29 CFR 1955.32 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 9 2013-07-01 2013-07-01 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...

40 CFR 27.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 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...

14 CFR 1264.120 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 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.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 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...

40 CFR 27.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 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...

14 CFR 1264.120 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true 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...

24 CFR 26.18 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

15 CFR 719.10 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

49 CFR 386.37 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 5 2014-10-01 2014-10-01 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...

49 CFR 1503.633 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 9 2011-10-01 2011-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or approval of the ALJ, at...

22 CFR 128.6 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 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...

40 CFR 27.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 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...

22 CFR 128.6 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 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...

49 CFR 1503.633 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 9 2013-10-01 2013-10-01 false Discovery. 1503.633 Section 1503.633... Rules of Practice in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or approval of the ALJ, at...

24 CFR 26.42 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

24 CFR 26.18 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

15 CFR 719.10 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 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...

22 CFR 128.6 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 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...

29 CFR 1955.32 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 9 2012-07-01 2012-07-01 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...

37 CFR 41.150 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 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...

49 CFR 386.37 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 5 2013-10-01 2013-10-01 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...

14 CFR 13.220 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or...

49 CFR 386.37 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 5 2012-10-01 2012-10-01 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...

24 CFR 26.18 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

14 CFR 13.220 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 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 386.37 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 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...

15 CFR 719.10 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 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...

14 CFR 13.220 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or...

49 CFR 604.38 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 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...

49 CFR 604.38 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 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...

14 CFR 13.220 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Discovery. 13.220 Section 13.220... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery described in this section, without the consent or...

24 CFR 26.18 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

49 CFR 604.38 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 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...

37 CFR 41.150 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 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...

37 CFR 41.150 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

24 CFR 26.18 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

49 CFR 604.38 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

49 CFR 1503.633 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

24 CFR 26.42 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

29 CFR 1955.32 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-07-01

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

22 CFR 128.6 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

15 CFR 719.10 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

42 CFR 426.532 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

14 CFR 13.220 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

40 CFR 27.21 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

14 CFR 1264.120 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

Accessing external innovation in drug discovery and development.

PubMed

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.

39 CFR 955.15 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

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

42 CFR 426.432 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Discovery. 426.432 Section 426.432 Public Health... an LCD § 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...

15 CFR 280.210 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Discovery. 280.210 Section 280.210... Enforcement § 280.210 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...

31 CFR 10.71 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 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...

49 CFR 1121.2 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 8 2014-10-01 2014-10-01 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...

10 CFR 13.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 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...

15 CFR 280.210 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Discovery. 280.210 Section 280.210... Enforcement § 280.210 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...

22 CFR 521.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 2 2013-04-01 2009-04-01 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...

10 CFR 13.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Discovery. 13.21 Section 13.21 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.21 Discovery. (a) The following types of discovery are...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...

38 CFR 42.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 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...

39 CFR 955.15 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

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

49 CFR 1121.2 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 8 2013-10-01 2013-10-01 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...

22 CFR 521.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 2 2014-04-01 2014-04-01 false 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.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 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...

15 CFR 766.9 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 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...

39 CFR 955.15 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

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

49 CFR 1121.2 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 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...

49 CFR 1121.2 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 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...

42 CFR 426.432 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 3 2012-10-01 2012-10-01 false Discovery. 426.432 Section 426.432 Public Health... an LCD § 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...

37 CFR 41.150 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Discovery. 41.150 Section 41... COMMERCE PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Contested Cases § 41.150 Discovery. (a) Limited discovery. A party is not entitled to discovery except as authorized in this subpart. The parties may agree...

10 CFR 13.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 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...

39 CFR 955.15 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

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

43 CFR 35.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 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...

43 CFR 35.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 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.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 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...

43 CFR 35.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-10-01

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

22 CFR 521.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 2 2012-04-01 2009-04-01 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.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 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...

15 CFR 280.210 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Discovery. 280.210 Section 280.210... Enforcement § 280.210 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...

38 CFR 42.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Discovery. 42.21 Section... 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...

15 CFR 766.9 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 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...

42 CFR 426.532 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 3 2012-10-01 2012-10-01 false Discovery. 426.532 Section 426.532 Public Health... an NCD § 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...

31 CFR 10.71 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 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...

37 CFR 41.150 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Discovery. 41.150 Section 41... COMMERCE PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Contested Cases § 41.150 Discovery. (a) Limited discovery. A party is not entitled to discovery except as authorized in this subpart. The parties may agree...

15 CFR 280.210 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Discovery. 280.210 Section 280.210... Enforcement § 280.210 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...

10 CFR 13.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 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...

22 CFR 521.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 2 2011-04-01 2009-04-01 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...

38 CFR 42.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 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...

15 CFR 766.9 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 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...

38 CFR 42.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 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...

42 CFR 426.532 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Discovery. 426.532 Section 426.532 Public Health... an NCD § 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...

22 CFR 521.21 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

39 CFR 955.15 - Discovery.

Code of Federal Regulations, 2010 CFR

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.

Code of Federal Regulations, 2010 CFR

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.

Code of Federal Regulations, 2010 CFR

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...

42 CFR 426.432 - Discovery.

Code of Federal Regulations, 2010 CFR

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.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

49 CFR 1121.2 - Discovery.

Code of Federal Regulations, 2010 CFR

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.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Discovery. 42.21 Section... 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...

Accelerating early anti-tuberculosis drug discovery by creating mycobacterial indicator strains that predict mode of action.

PubMed

Boot, Maikel; Commandeur, Susanna; Subudhi, Amit K; Bahira, Meriem; Smith, Trever C; Abdallah, Abdallah M; van Gemert, Mae; Lelièvre, Joël; Ballell, Lluís; Aldridge, Bree B; Pain, Arnab; Speer, Alexander; Bitter, Wilbert

2018-04-16

Due to the rise of drug resistant forms of tuberculosis there is an urgent need for novel antibiotics to effectively combat these cases and shorten treatment regimens. Recently, drug screens using whole cell analyses have been shown to be successful. However, current high-throughput screens focus mostly on stricto sensu life-death screening that give little qualitative information. In doing so, promising compound scaffolds or non-optimized compounds that fail to reach inhibitory concentrations are missed. To accelerate early TB drug discovery, we performed RNA sequencing on Mycobacterium tuberculosis and Mycobacterium marinum to map the stress responses that follow upon exposure to sub-inhibitory concentrations of antibiotics with known targets: ciprofloxacin, ethambutol, isoniazid, streptomycin and rifampicin. The resulting dataset comprises the first overview of transcriptional stress responses of mycobacteria to different antibiotics. We show that antibiotics can be distinguished based on their specific transcriptional stress fingerprint. Notably, this fingerprint was more distinctive in M. marinum. We decided to use this to our advantage and continue with this model organism. A selection of diverse antibiotic stress genes was used to construct stress reporters. In total, three functional reporters were constructed to respond to DNA damage, cell wall damage and ribosomal inhibition. Subsequently, these reporter strains were used to screen a small anti-TB compound library to predict the mode of action. In doing so, we could identify the putative mode of action for three novel compounds, which confirms our approach. Copyright © 2018 American Society for Microbiology.

Perfect launch for Space Shuttle Discovery on mission STS-105

NASA Technical Reports Server (NTRS)

2001-01-01

KENNEDY SPACE CENTER, Fla. -- Viewed from between the trees, Space Shuttle Discovery rises above the smoke as it soars into the blue sky on mission STS-105 to the International Space Station. Viewed from the top of the Vehicle Assembly Building, liftoff occurred at 5:10:14 p.m. EDT on this second launch attempt. Launch countdown activities for the 12-day mission were called off Aug. 9 during the T-9 minute hold due to the high potential for lightning, a thick cloud cover and the potential for showers. Besides the Shuttle crew of four, Discovery carries the Expedition Three crew who will replace Expedition Two on the International Space Station. The mission includes the third flight of an Italian-built Multi-Purpose Logistics Module delivering additional scientific racks, equipment and supplies for the Space Station, and two spacewalks. Part of the payload is the Early Ammonia Servicer (EAS) tank, which will be attached to the Station during the spacewalks. The EAS contains spare ammonia for the Station'''s cooling system. The three-member Expedition Two crew will be returning to Earth aboard Discovery after a five-month stay on the Station.

Perfect launch for Space Shuttle Discovery on mission STS-105

NASA Technical Reports Server (NTRS)

2001-01-01

KENNEDY SPACE CENTER, Fla. -- Trailing a fiery-looking column of smoke, Space Shuttle Discovery hurtles into a blue sky on mission STS-105 to the International Space Station. Viewed from the top of the Vehicle Assembly Building, liftoff occurred at 5:10:14 p.m. EDT on this second launch attempt. Launch countdown activities for the 12-day mission were called off Aug. 9 during the T-9 minute hold due to the high potential for lightning, a thick cloud cover and the potential for showers. Besides the Shuttle crew of four, Discovery carries the Expedition Three crew who will replace Expedition Two on the International Space Station. The mission includes the third flight of an Italian-built Multi-Purpose Logistics Module delivering additional scientific racks, equipment and supplies for the Space Station, and two spacewalks. Part of the payload is the Early Ammonia Servicer (EAS) tank, which will be attached to the Station during the spacewalks. The EAS contains spare ammonia for the Station'''s cooling system. The three-member Expedition Two crew will be returning to Earth aboard Discovery after a five-month stay on the Station.

Discovery and Classification in Astronomy

NASA Astrophysics Data System (ADS)

Dick, Steven J.

2012-01-01

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

Get Involved in Planetary Discoveries through New Worlds, New Discoveries

NASA Astrophysics Data System (ADS)

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

2013-01-01

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

31 CFR 16.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 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...

31 CFR 16.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 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...

31 CFR 16.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 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...

43 CFR 35.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Discovery. 35.21 Section 35.21 Public Lands... STATEMENTS § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...

31 CFR 16.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 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...

13 CFR 134.213 - Discovery.

Code of Federal Regulations, 2010 CFR

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.

Code of Federal Regulations, 2010 CFR

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...

The Discovery of the b Quark at Fermilab in 1977: The Experiment Coordinator's Story

DOE R&D Accomplishments Database

Yoh, J.

1997-12-01

I present the history of the discovery of the Upsilon ({Upsilon}) particle (the first member of the b-quark family to be observed) at Fermilab in 1977 by the CFS (Columbia-Fermilab-Stony Brook collaboration) E288 experiment headed by Leon Lederman. We found the first evidence of the {Upsilon} in November 1976 in an early phase of E288. The subsequent discovery in the spring of 1977 resulted from an upgraded E288 the {mu}{mu}II phase, optimized for dimuons, with about 100 times the sensitivity of the previous investigatory dimuon phase (which had been optimized for dielectrons). The events leading to the discovery, the planning of {mu}{mu}II and the running, including a misadventure (the infamous Shunt Fire of May 1977), are described. Some discussions of the aftermath, a summary, and an acknowledgement list end this brief historical note.

13 CFR 134.213 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Discovery. 134.213 Section 134.213... OFFICE OF HEARINGS AND APPEALS Rules of Practice § 134.213 Discovery. (a) Motion. A party may obtain discovery only upon motion, and for good cause shown. (b) Forms. The forms of discovery which a Judge can...

13 CFR 134.213 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Discovery. 134.213 Section 134.213... OFFICE OF HEARINGS AND APPEALS Rules of Practice § 134.213 Discovery. (a) Motion. A party may obtain discovery only upon motion, and for good cause shown. (b) Forms. The forms of discovery which a Judge can...

13 CFR 134.213 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Discovery. 134.213 Section 134.213... OFFICE OF HEARINGS AND APPEALS Rules of Practice § 134.213 Discovery. (a) Motion. A party may obtain discovery only upon motion, and for good cause shown. (b) Forms. The forms of discovery which a Judge can...

13 CFR 134.213 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Discovery. 134.213 Section 134.213... OFFICE OF HEARINGS AND APPEALS Rules of Practice § 134.213 Discovery. (a) Motion. A party may obtain discovery only upon motion, and for good cause shown. (b) Forms. The forms of discovery which a Judge can...

Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics

PubMed Central

Kocevar, Nina; Komel, Radovan

2014-01-01

Despite remarkable progress in proteomic methods, including improved detection limits and sensitivity, these methods have not yet been established in routine clinical practice. The main limitations, which prevent their integration into clinics, are high cost of equipment, the need for highly trained personnel, and last, but not least, the establishment of reliable and accurate protein biomarkers or panels of protein biomarkers for detection of neoplasms. Furthermore, the complexity and heterogeneity of most solid tumours present obstacles in the discovery of specific protein signatures, which could be used for early detection of cancers, for prediction of disease outcome, and for determining the response to specific therapies. However, cancer proteome, as the end-point of pathological processes that underlie cancer development and progression, could represent an important source for the discovery of new biomarkers and molecular targets for tailored therapies. PMID:24550697

UCSF Small Molecule Discovery Center: innovation, collaboration and chemical biology in the Bay Area.

PubMed

Arkin, Michelle R; Ang, Kenny K H; Chen, Steven; Davies, Julia; Merron, Connie; Tang, Yinyan; Wilson, Christopher G M; Renslo, Adam R

2014-05-01

The Small Molecule Discovery Center (SMDC) at the University of California, San Francisco, works collaboratively with the scientific community to solve challenging problems in chemical biology and drug discovery. The SMDC includes a high throughput screening facility, medicinal chemistry, and research labs focused on fundamental problems in biochemistry and targeted drug delivery. Here, we outline our HTS program and provide examples of chemical tools developed through SMDC collaborations. We have an active research program in developing quantitative cell-based screens for primary cells and whole organisms; here, we describe whole-organism screens to find drugs against parasites that cause neglected tropical diseases. We are also very interested in target-based approaches for so-called "undruggable", protein classes and fragment-based lead discovery. This expertise has led to several pharmaceutical collaborations; additionally, the SMDC works with start-up companies to enable their early-stage research. The SMDC, located in the biotech-focused Mission Bay neighborhood in San Francisco, is a hub for innovative small-molecule discovery research at UCSF.

29 CFR 2700.56 - Discovery; general.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 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... upon property for inspecting, copying, photographing, and gathering information. (b) Scope of discovery...

29 CFR 2700.56 - Discovery; general.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 9 2012-07-01 2012-07-01 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... upon property for inspecting, copying, photographing, and gathering information. (b) Scope of discovery...

29 CFR 2700.56 - Discovery; general.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 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... upon property for inspecting, copying, photographing, and gathering information. (b) Scope of discovery...

29 CFR 2700.56 - Discovery; general.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 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... upon property for inspecting, copying, photographing, and gathering information. (b) Scope of discovery...

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

PubMed

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.

Ensemble docking to difficult targets in early-stage drug discovery: Methodology and application to fibroblast growth factor 23.

PubMed

Velazquez, Hector A; Riccardi, Demian; Xiao, Zhousheng; Quarles, Leigh Darryl; Yates, Charless Ryan; Baudry, Jerome; Smith, Jeremy C

2018-02-01

Ensemble docking is now commonly used in early-stage in silico drug discovery and can be used to attack difficult problems such as finding lead compounds which can disrupt protein-protein interactions. We give an example of this methodology here, as applied to fibroblast growth factor 23 (FGF23), a protein hormone that is responsible for regulating phosphate homeostasis. The first small-molecule antagonists of FGF23 were recently discovered by combining ensemble docking with extensive experimental target validation data (Science Signaling, 9, 2016, ra113). Here, we provide a detailed account of how ensemble-based high-throughput virtual screening was used to identify the antagonist compounds discovered in reference (Science Signaling, 9, 2016, ra113). Moreover, we perform further calculations, redocking those antagonist compounds identified in reference (Science Signaling, 9, 2016, ra113) that performed well on drug-likeness filters, to predict possible binding regions. These predicted binding modes are rescored with the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) approach to calculate the most likely binding site. Our findings suggest that the antagonist compounds antagonize FGF23 through the disruption of protein-protein interactions between FGF23 and fibroblast growth factor receptor (FGFR). © 2017 John Wiley & Sons A/S.

Purposive discovery of operations

NASA Technical Reports Server (NTRS)

Sims, Michael H.; Bresina, John L.

1992-01-01

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

Decades of Discovery

DOE R&D Accomplishments Database

2011-06-01

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

The Tuberculosis Drug Discovery and Development Pipeline and Emerging Drug Targets

PubMed Central

Mdluli, Khisimuzi; Kaneko, Takushi; Upton, Anna

2015-01-01

The recent accelerated approval for use in extensively drug-resistant and multidrug-resistant-tuberculosis (MDR-TB) of two first-in-class TB drugs, bedaquiline and delamanid, has reinvigorated the TB drug discovery and development field. However, although several promising clinical development programs are ongoing to evaluate new TB drugs and regimens, the number of novel series represented is few. The global early-development pipeline is also woefully thin. To have a chance of achieving the goal of better, shorter, safer TB drug regimens with utility against drug-sensitive and drug-resistant disease, a robust and diverse global TB drug discovery pipeline is key, including innovative approaches that make use of recently acquired knowledge on the biology of TB. Fortunately, drug discovery for TB has resurged in recent years, generating compounds with varying potential for progression into developable leads. In parallel, advances have been made in understanding TB pathogenesis. It is now possible to apply the lessons learned from recent TB hit generation efforts and newly validated TB drug targets to generate the next wave of TB drug leads. Use of currently underexploited sources of chemical matter and lead-optimization strategies may also improve the efficiency of future TB drug discovery. Novel TB drug regimens with shorter treatment durations must target all subpopulations of Mycobacterium tuberculosis existing in an infection, including those responsible for the protracted TB treatment duration. This review summarizes the current TB drug development pipeline and proposes strategies for generating improved hits and leads in the discovery phase that could help achieve this goal. PMID:25635061

4 CFR 28.43 - Compelling discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 4 Accounts 1 2011-01-01 2011-01-01 false Compelling discovery. 28.43 Section 28.43 Accounts... Procedures Discovery § 28.43 Compelling discovery. (a) Motion for an order compelling discovery. Motions for orders compelling discovery shall be submitted to the administrative judge as set forth at § 28.42(c)(2...

Pregnancy discovery and acceptance among low-income primiparous women: a multicultural exploration.

PubMed

Peacock, N R; Kelley, M A; Carpenter, C; Davis, M; Burnett, G; Chavez, N; Aranda, V

2001-06-01

As part of a larger study exploring psychosocial factors that influence self-care and use of health care services during pregnancy, we investigated the process of pregnancy discovery and acceptance among a culturally diverse group of women who had given birth to their first child in the year preceding data collection. Eighty-seven low-income women from four cultural groups (African American, Mexican, Puerto Rican, and white) participated in eight focus groups held in their communities. The focus groups were ethnically homogenous and stratified by early and late entry into prenatal care. A social influence model guided the development of focus group questions, and the study followed a participatory action research model, with community members involved in all phases of the research. Issues that emerged from the focus groups as possible influences on timing of pregnancy recognition include the role of pregnancy signs and symptoms and pregnancy risk perception in the discovery process, the role of social network members in labeling and affirming the pregnancy, concerns about disclosure, "planning" status of the pregnancy, and perceived availability of choices for resolving an unintended pregnancy. The pregnancy discovery process is complex, and when protracted, can potentially result in delayed initiation of both prenatal care and healthful pregnancy behaviors. Enhancing our understanding of pregnancy discovery and acceptance has clear implications for primary and secondary prevention. Future research is needed to further explain the trajectory of pregnancy discovery and acceptance and its influence on health behaviors and pregnancy outcome.

Metabolomics for Biomarker Discovery: Moving to the Clinic

PubMed Central

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

2015-01-01

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

A brief history of Alzheimer's disease gene discovery.

PubMed

Tanzi, Rudolph E

2013-01-01

The rich and colorful history of gene discovery in Alzheimer's disease (AD) over the past three decades is as complex and heterogeneous as the disease, itself. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations inAPP, PSEN1, and PSEN2 are fully penetrant for early-onset (<60 years) familial AD, which represents <5% of AD. On the other hand, common gene polymorphisms, such as the 4 and 2 variants of the APOE gene, influence susceptibility for common (>95%) late-onset AD. These four genes account for 30-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of additional highly confirmed AD candidate genes. Here, I review the past, present, and future of attempts to elucidate the complex and heterogeneous genetic underpinnings of AD along with some of the unique events that made these discoveries possible.

NASA's Discovery Program

NASA Astrophysics Data System (ADS)

Kicza, Mary; Bruegge, Richard Vorder

1995-01-01

NASA's Discovery Program represents an new era in planetary exploration. Discovery's primary goal: to maintain U.S. scientific leadership in planetary research by conducting a series of highly focused, cost effective missions to answer critical questions in solar system science. The Program will stimulate the development of innovative management approaches by encouraging new teaming arrangements among industry, universities and the government. The program encourages the prudent use of new technologies to enable/enhance science return and to reduce life cycle cost, and it supports the transfer of these technologies to the private sector for secondary applications. The Near-Earth Asteroid Rendezvous and Mars Pathfinder missions have been selected as the first two Discovery missions. Both will be launched in 1996. Subsequent, competitively selected missions will be conceived and proposed to NASA by teams of scientists and engineers from industry, academia, and government organizations. This paper summarizes the status of Discovery Program planning.

Music Experiences in Early Childhood.

ERIC Educational Resources Information Center

Andress, Barbara

This book presents a program of music experiences for young children (3-5-year-olds) which focuses on an experiential discovery approach to music, rather than on imposing ideas and a repertoire on the child. Early sections of the book discuss the importance of the child-centered music program, its process and characteristics, and the role of the…

Incorporation of rapid thermodynamic data in fragment-based drug discovery.

PubMed

Kobe, Akihiro; Caaveiro, Jose M M; Tashiro, Shinya; Kajihara, Daisuke; Kikkawa, Masato; Mitani, Tomoya; Tsumoto, Kouhei

2013-03-14

Fragment-based drug discovery (FBDD) has enjoyed increasing popularity in recent years. We introduce SITE (single-injection thermal extinction), a novel thermodynamic methodology that selects high-quality hits early in FBDD. SITE is a fast calorimetric competitive assay suitable for automation that captures the essence of isothermal titration calorimetry but using significantly fewer resources. We describe the principles of SITE and identify a novel family of fragment inhibitors of the enzyme ketosteroid isomerase displaying high values of enthalpic efficiency.

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

ERIC Educational Resources Information Center

Foster, Anita K.; MacDonald, Jean B.

2013-01-01

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

EDITORIAL: Nobel Prize in Physiology or Medicine 2003 awarded to Paul Lauterbur and Peter Mansfield for discoveries concerning magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Leach, Martin O.

2004-02-01

The award of the Nobel Prize in Physiology or Medicine recognizes discoveries concerning the use of magnetic resonance to visualize different structures. The Assembly's decision to recognize the discoveries underpinning efficient spatial mapping of biological properties reflects the singular importance of imaging to the medical application of this technique. Without this, abnormalities in morphology cannot be recognized. Equally, the wealth of physiological information that can be obtained by manipulation of the magnetic resonance signal is of little value unless localized to identified organs, pathology or areas of tissue. Based on these early discoveries, a wide range of imaging and measurement techniques, together with enabling instrumentation, have been developed over the last 30 years. Commercial equipment became available in the early 1980s, and some 60 million MRI examinations are now performed each year. The power of the technique, and the range of applications, continues to develop rapidly. The full text of this editorial is given in the PDF file below.

29 CFR 2200.208 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 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...

49 CFR 209.313 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 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...

47 CFR 65.105 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Discovery. 65.105 Section 65.105... 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.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 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...

47 CFR 65.105 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Discovery. 65.105 Section 65.105... 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.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 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...

29 CFR 2200.208 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 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.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Discovery. 65.105 Section 65.105... 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...

29 CFR 2200.208 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 9 2012-07-01 2012-07-01 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...

29 CFR 2200.208 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 9 2013-07-01 2013-07-01 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...

49 CFR 209.313 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 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...

47 CFR 65.105 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Discovery. 65.105 Section 65.105... 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.

Code of Federal Regulations, 2010 CFR

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...

29 CFR 2200.208 - Discovery.

Code of Federal Regulations, 2010 CFR

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.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Discovery. 65.105 Section 65.105... 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...

Quantifying the Ease of Scientific Discovery

PubMed Central

Arbesman, Samuel

2012-01-01

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

Quantifying the Ease of Scientific Discovery.

PubMed

Arbesman, Samuel

2011-02-01

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

Direct investigations of supersymmetry: subgroup summary report

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

Stephen P Martin et al.

A recurring element of the discussions in the Snowmass study is that there is a need and opportunity for improved theoretical tools in preparation for the discovery of Supersymmetry (SUSY). In order to be competitive with mass measurements at the LHC and a linear collider (LC), predictions of sparticle and Higgs masses from given model parameters need to be improved by an order of magnitude in some cases. There is also room for growth and improvement in (Monte Carlo) SUSY event generators. It seems injudicious to discuss priorities in the field of direct SUSY detection independently of having established directlymore » the existence and mass of the Higgs since it is the particle that led to the founding of SUSY models. But under the hypothesis that a light Higgs exists with mass compatible with SUSY, then they should discuss such priorities. As outlined in section III in the context of the flavor-respecting minimal supersymmetric standard model (MSSM), there is no fundamental symmetry to tie, e.g., squark masses to slepton masses, or the gluino mass to the chargino mass or the chargino mass to the neutralino mass. However, models such as mSUGRA do lead to such relationships and LHC studies show that the heaviest super-partners, the squarks and the gluino should be observable for masses up to about 2.5 TeV at the LHC in such models. Depending on the actual decay chains, some other superpartners may be identifiable in the cascade decays of the quarks and the gluino. On the other hand a LC with CM energy of 1 TeV could comprehensively explore and discover superpartners with masses less than 0.5 TeV largely independently of their nature (neutral, charged, strong, electroweak) and decay modes. In most supersymmetric models, the chargino and neutralino and often the sleptons are much lighter than the squarks and gluino. A VLHC could extend the mass reach for squarks and the gluino but would not necessarily add much value if these had already been seen at the LHC. In

Molecular genetics of early-onset Alzheimer's disease revisited.

PubMed

Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

2016-06-01

As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

12 CFR 1209.29 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the timely, cost-effective management of document discovery (including, if applicable, electronically... discovery plan shall specify the form of electronic productions, if any. Documents are to be produced in... proceeding under this part may obtain document discovery by serving upon any other party in the proceeding a...

12 CFR 1209.29 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the timely, cost-effective management of document discovery (including, if applicable, electronically... discovery plan shall specify the form of electronic productions, if any. Documents are to be produced in... proceeding under this part may obtain document discovery by serving upon any other party in the proceeding a...

12 CFR 1209.29 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the timely, cost-effective management of document discovery (including, if applicable, electronically... discovery plan shall specify the form of electronic productions, if any. Documents are to be produced in... proceeding under this part may obtain document discovery by serving upon any other party in the proceeding a...

15 CFR 280.210 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

46 CFR 550.502 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 9 2011-10-01 2011-10-01 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...

46 CFR 550.502 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 9 2014-10-01 2014-10-01 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...

29 CFR 2700.107 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 9 2013-07-01 2013-07-01 false Discovery. 2700.107 Section 2700.107 Labor Regulations Relating to Labor (Continued) FEDERAL MINE SAFETY AND HEALTH REVIEW COMMISSION PROCEDURAL RULES Simplified Proceedings § 2700.107 Discovery. Discovery is not permitted except as ordered by the Administrative Law Judge. ...

29 CFR 2700.107 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 false Discovery. 2700.107 Section 2700.107 Labor Regulations Relating to Labor (Continued) FEDERAL MINE SAFETY AND HEALTH REVIEW COMMISSION PROCEDURAL RULES Simplified Proceedings § 2700.107 Discovery. Discovery is not permitted except as ordered by the Administrative Law Judge. ...

22 CFR 35.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 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...

10 CFR 1013.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 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...

15 CFR 785.8 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Discovery. 785.8 Section 785.8... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter, not...

45 CFR 96.65 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 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.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 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...

37 CFR 2.120 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 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...

29 CFR 2700.107 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Discovery. 2700.107 Section 2700.107 Labor Regulations Relating to Labor (Continued) FEDERAL MINE SAFETY AND HEALTH REVIEW COMMISSION PROCEDURAL RULES Simplified Proceedings § 2700.107 Discovery. Discovery is not permitted except as ordered by the Administrative Law Judge. ...

10 CFR 1013.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 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...

22 CFR 35.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 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...

10 CFR 1013.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 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...

45 CFR 96.65 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 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. ...

37 CFR 2.120 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 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...

37 CFR 42.51 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Discovery. 42.51 Section 42... Production § 42.51 Discovery. (a) Mandatory initial disclosures. (1) With agreement. Parties may agree to mandatory discovery requiring the initial disclosures set forth in the Office Patent Trial Practice Guide...

37 CFR 2.120 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Discovery. 2.120 Section 2... 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...

49 CFR 31.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 1 2012-10-01 2012-10-01 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...

37 CFR 42.51 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Discovery. 42.51 Section 42... Production § 42.51 Discovery. (a) Mandatory initial disclosures. (1) With agreement. Parties may agree to mandatory discovery requiring the initial disclosures set forth in the Office Patent Trial Practice Guide...

45 CFR 96.65 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 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. ...

10 CFR 1013.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 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.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 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...

22 CFR 35.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 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.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 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.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 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...

15 CFR 785.8 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 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...

46 CFR 550.502 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 9 2012-10-01 2012-10-01 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.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Discovery. 785.8 Section 785.8... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery. (a) General. The parties are encouraged to engage in voluntary discovery regarding any matter, not...

29 CFR 2700.107 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 9 2012-07-01 2012-07-01 false Discovery. 2700.107 Section 2700.107 Labor Regulations Relating to Labor (Continued) FEDERAL MINE SAFETY AND HEALTH REVIEW COMMISSION PROCEDURAL RULES Simplified Proceedings § 2700.107 Discovery. Discovery is not permitted except as ordered by the Administrative Law Judge. ...

22 CFR 35.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 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...

46 CFR 550.502 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 9 2013-10-01 2013-10-01 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.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 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...

49 CFR 31.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 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...

45 CFR 96.65 - Discovery.

Code of Federal Regulations, 2010 CFR

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. ...

46 CFR 550.502 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

22 CFR 35.21 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

10 CFR 1013.21 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

15 CFR 785.8 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

37 CFR 2.120 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

43 CFR 4.1130 - Discovery methods.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 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...

43 CFR 4.1130 - Discovery methods.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

43 CFR 4.1130 - Discovery methods.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Discovery methods. 4.1130 Section 4.1130... Special Rules Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by one or more of the following methods— (a) Depositions upon oral...

43 CFR 4.1130 - Discovery methods.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 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...

43 CFR 4.1130 - Discovery methods.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true 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...

12 CFR 263.53 - Discovery depositions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Discovery depositions. 263.53 Section 263.53... Discovery depositions. (a) In general. In addition to the discovery permitted in subpart A of this part, limited discovery by means of depositions shall be allowed for individuals with knowledge of facts...

36 CFR § 1150.63 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Discovery. § 1150.63 Section... BOARD 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...

12 CFR 263.53 - Discovery depositions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Discovery depositions. 263.53 Section 263.53... Discovery depositions. (a) In general. In addition to the discovery permitted in subpart A of this part, limited discovery by means of depositions shall be allowed for individuals with knowledge of facts...

Can Functional Magnetic Resonance Imaging Improve Success Rates in CNS Drug Discovery?

PubMed Central

Borsook, David; Hargreaves, Richard; Becerra, Lino

2011-01-01

Introduction The bar for developing new treatments for CNS disease is getting progressively higher and fewer novel mechanisms are being discovered, validated and developed. The high costs of drug discovery necessitate early decisions to ensure the best molecules and hypotheses are tested in expensive late stage clinical trials. The discovery of brain imaging biomarkers that can bridge preclinical to clinical CNS drug discovery and provide a ‘language of translation’ affords the opportunity to improve the objectivity of decision-making. Areas Covered This review discusses the benefits, challenges and potential issues of using a science based biomarker strategy to change the paradigm of CNS drug development and increase success rates in the discovery of new medicines. The authors have summarized PubMed and Google Scholar based publication searches to identify recent advances in functional, structural and chemical brain imaging and have discussed how these techniques may be useful in defining CNS disease state and drug effects during drug development. Expert opinion The use of novel brain imaging biomarkers holds the bold promise of making neuroscience drug discovery smarter by increasing the objectivity of decision making thereby improving the probability of success of identifying useful drugs to treat CNS diseases. Functional imaging holds the promise to: (1) define pharmacodynamic markers as an index of target engagement (2) improve translational medicine paradigms to predict efficacy; (3) evaluate CNS efficacy and safety based on brain activation; (4) determine brain activity drug dose-response relationships and (5) provide an objective evaluation of symptom response and disease modification. PMID:21765857

40 CFR 164.51 - Other discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Other discovery. 164.51 Section 164.51... (Other Than Expedited Hearings) Prehearing Procedures and Discovery § 164.51 Other discovery. (a) General. Except as so provided by § 164.50(b) supra, further discovery, under this subpart, shall be permitted...

40 CFR 164.51 - Other discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Other discovery. 164.51 Section 164.51... (Other Than Expedited Hearings) Prehearing Procedures and Discovery § 164.51 Other discovery. (a) General. Except as so provided by § 164.50(b) supra, further discovery, under this subpart, shall be permitted...

45 CFR 79.21 - Discovery.

Code of Federal Regulations, 2010 CFR

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...

45 CFR 1386.103 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 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...

34 CFR 33.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 1 2013-07-01 2013-07-01 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...

34 CFR 33.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 1 2012-07-01 2012-07-01 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...

20 CFR 355.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true 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...

34 CFR 33.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 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...

6 CFR 13.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 6 Domestic Security 1 2014-01-01 2014-01-01 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 79.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 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...

28 CFR 18.7 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 1 2014-07-01 2014-07-01 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...

28 CFR 18.7 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 1 2012-07-01 2012-07-01 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...

6 CFR 13.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

7 CFR 283.12 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 4 2011-01-01 2011-01-01 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...

28 CFR 71.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 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...