Dynamic model of target charging by short laser pulse interactions.

PubMed

Poyé, A; Dubois, J-L; Lubrano-Lavaderci, F; D'Humières, E; Bardon, M; Hulin, S; Bailly-Grandvaux, M; Ribolzi, J; Raffestin, D; Santos, J J; Nicolaï, Ph; Tikhonchuk, V

2015-10-01

A model providing an accurate estimate of the charge accumulation on the surface of a metallic target irradiated by a high-intensity laser pulse of fs-ps duration is proposed. The model is confirmed by detailed comparisons with specially designed experiments. Such a model is useful for understanding the electromagnetic pulse emission and the quasistatic magnetic field generation in laser-plasma interaction experiments.

Deep-Learning-Based Drug-Target Interaction Prediction.

PubMed

Wen, Ming; Zhang, Zhimin; Niu, Shaoyu; Sha, Haozhi; Yang, Ruihan; Yun, Yonghuan; Lu, Hongmei

2017-04-07

Identifying interactions between known drugs and targets is a major challenge in drug repositioning. In silico prediction of drug-target interaction (DTI) can speed up the expensive and time-consuming experimental work by providing the most potent DTIs. In silico prediction of DTI can also provide insights about the potential drug-drug interaction and promote the exploration of drug side effects. Traditionally, the performance of DTI prediction depends heavily on the descriptors used to represent the drugs and the target proteins. In this paper, to accurately predict new DTIs between approved drugs and targets without separating the targets into different classes, we developed a deep-learning-based algorithmic framework named DeepDTIs. It first abstracts representations from raw input descriptors using unsupervised pretraining and then applies known label pairs of interaction to build a classification model. Compared with other methods, it is found that DeepDTIs reaches or outperforms other state-of-the-art methods. The DeepDTIs can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.

Computation of shock wave/target interaction

NASA Technical Reports Server (NTRS)

Mark, A.; Kutler, P.

1983-01-01

Computational results of shock waves impinging on targets and the ensuing diffraction flowfield are presented. A number of two-dimensional cases are computed with finite difference techniques. The classical case of a shock wave/cylinder interaction is compared with shock tube data and shows the quality of the computations on a pressure-time plot. Similar results are obtained for a shock wave/rectangular body interaction. Here resolution becomes important and the use of grid clustering techniques tend to show good agreement with experimental data. Computational results are also compared with pressure data resulting from shock impingement experiments for a complicated truck-like geometry. Here of significance are the grid generation and clustering techniques used. For these very complicated bodies, grids are generated by numerically solving a set of elliptic partial differential equations.

High energy density physics effects predicted in simulations of the CERN HiRadMat beam-target interaction experiments

NASA Astrophysics Data System (ADS)

Tahir, N. A.; Burkart, F.; Schmidt, R.; Shutov, A.; Wollmann, D.; Piriz, A. R.

2016-12-01

Experiments have been done at the CERN HiRadMat (High Radiation to Materials) facility in which large cylindrical copper targets were irradiated with 440 GeV proton beam generated by the Super Proton Synchrotron (SPS). The primary purpose of these experiments was to confirm the existence of hydrodynamic tunneling of ultra-relativistic protons and their hadronic shower in solid materials, that was predicted by previous numerical simulations. The experimental measurements have shown very good agreement with the simulation results. This provides confidence in our simulations of the interaction of the 7 TeV LHC (Large Hadron Collider) protons and the 50 TeV Future Circular Collider (FCC) protons with solid materials, respectively. This work is important from the machine protection point of view. The numerical simulations have also shown that in the HiRadMat experiments, a significant part of thetarget material is be converted into different phases of High Energy Density (HED) matter, including two-phase solid-liquid mixture, expanded as well as compressed hot liquid phases, two-phase liquid-gas mixture and gaseous state. The HiRadMat facility is therefore a unique ion beam facility worldwide that is currently available for studying the thermophysical properties of HED matter. In the present paper we discuss the numerical simulation results and present a comparison with the experimental measurements.

Computational modeling of joint U.S.-Russian experiments relevant to magnetic compression/magnetized target fusion (MAGO/MTF)

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

Sheehey, P.T.; Faehl, R.J.; Kirkpatrick, R.C.

1997-12-31

Magnetized Target Fusion (MTF) experiments, in which a preheated and magnetized target plasma is hydrodynamically compressed to fusion conditions, present some challenging computational modeling problems. Recently, joint experiments relevant to MTF (Russian acronym MAGO, for Magnitnoye Obzhatiye, or magnetic compression) have been performed by Los Alamos National Laboratory and the All-Russian Scientific Research Institute of Experimental Physics (VNIIEF). Modeling of target plasmas must accurately predict plasma densities, temperatures, fields, and lifetime; dense plasma interactions with wall materials must be characterized. Modeling of magnetically driven imploding solid liners, for compression of target plasmas, must address issues such as Rayleigh-Taylor instability growthmore » in the presence of material strength, and glide plane-liner interactions. Proposed experiments involving liner-on-plasma compressions to fusion conditions will require integrated target plasma and liner calculations. Detailed comparison of the modeling results with experiment will be presented.« less

Testing light dark matter coannihilation with fixed-target experiments

DOE PAGES

Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan; ...

2017-09-01

In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and downscattering as well as decaymore » of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.« less

Testing light dark matter coannihilation with fixed-target experiments

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

Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan

In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and downscattering as well as decaymore » of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.« less

Testing light dark matter coannihilation with fixed-target experiments

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

Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan

In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and down-scattering as well as decaymore » of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.« less

SIMULATED PERFORMANCE OF THE PRODUCTION TARGET FOR THE MUON G-2 EXPERIMENT

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

Stratakis, D.; Convery, M.; Morgan, J. P.

The Muon g-2 Experiment plans to use the Fermilab Re-cycler Ring for forming the proton bunches that hit its pro-duction target. The proposed scheme uses one RF system, 80 kV of 2.5 MHz RF. In order to avoid bunch rotations in a mismatched bucket, the 2.5 MHz is ramped adiabatically from 3 to 80 kV in 90 ms. In this study, the interaction of the primary proton beam with the production target for the Muon g-2 Experiment is numerically examined.

Conducting interactive experiments online.

PubMed

Arechar, Antonio A; Gächter, Simon; Molleman, Lucas

2018-01-01

Online labor markets provide new opportunities for behavioral research, but conducting economic experiments online raises important methodological challenges. This particularly holds for interactive designs. In this paper, we provide a methodological discussion of the similarities and differences between interactive experiments conducted in the laboratory and online. To this end, we conduct a repeated public goods experiment with and without punishment using samples from the laboratory and the online platform Amazon Mechanical Turk. We chose to replicate this experiment because it is long and logistically complex. It therefore provides a good case study for discussing the methodological and practical challenges of online interactive experimentation. We find that basic behavioral patterns of cooperation and punishment in the laboratory are replicable online. The most important challenge of online interactive experiments is participant dropout. We discuss measures for reducing dropout and show that, for our case study, dropouts are exogenous to the experiment. We conclude that data quality for interactive experiments via the Internet is adequate and reliable, making online interactive experimentation a potentially valuable complement to laboratory studies.

Predicting Drug-Target Interactions With Multi-Information Fusion.

PubMed

Peng, Lihong; Liao, Bo; Zhu, Wen; Li, Zejun; Li, Keqin

2017-03-01

Identifying potential associations between drugs and targets is a critical prerequisite for modern drug discovery and repurposing. However, predicting these associations is difficult because of the limitations of existing computational methods. Most models only consider chemical structures and protein sequences, and other models are oversimplified. Moreover, datasets used for analysis contain only true-positive interactions, and experimentally validated negative samples are unavailable. To overcome these limitations, we developed a semi-supervised based learning framework called NormMulInf through collaborative filtering theory by using labeled and unlabeled interaction information. The proposed method initially determines similarity measures, such as similarities among samples and local correlations among the labels of the samples, by integrating biological information. The similarity information is then integrated into a robust principal component analysis model, which is solved using augmented Lagrange multipliers. Experimental results on four classes of drug-target interaction networks suggest that the proposed approach can accurately classify and predict drug-target interactions. Part of the predicted interactions are reported in public databases. The proposed method can also predict possible targets for new drugs and can be used to determine whether atropine may interact with alpha1B- and beta1- adrenergic receptors. Furthermore, the developed technique identifies potential drugs for new targets and can be used to assess whether olanzapine and propiomazine may target 5HT2B. Finally, the proposed method can potentially address limitations on studies of multitarget drugs and multidrug targets.

Interactions between Impacting Particles and Target in Two-Phase Flow

NASA Astrophysics Data System (ADS)

Kang, Sang-Wook; Chow, Tze-Show

1996-11-01

The time-dependent interaction phenomena between a target and the incident solid particles borne by supersonic gas-jet stream have been numerically analyzed. In particular, the analysis dealt with particles such as aluminum, copper, and uranium ipinging on aluminum, copper, or uranium targets at various impact velocities ranging from 200 m/s to 1,000 m/s. Typical particle sizes were 50 to 100 micrometers. Results show considerable deformation of both the incident particles and the target when the velocity is greater than 500 m/s. Experiments performed on copper particles impacting an aluminum target demonstrate that under certain conditions (such as a supersonic gas jet issuing from a nozzle carrying solid particles) the impacts not only deform but also cause deposition of the particles on the surface. The present analysis shows the plausibility of such behavior when the particles impact the target at high velocities.

Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features

PubMed Central

Shi, Xiao-He; Hu, Le-Le; Kong, Xiangyin; Cai, Yu-Dong; Chou, Kuo-Chen

2010-01-01

Background Study of drug-target interaction networks is an important topic for drug development. It is both time-consuming and costly to determine compound-protein interactions or potential drug-target interactions by experiments alone. As a complement, the in silico prediction methods can provide us with very useful information in a timely manner. Methods/Principal Findings To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties. The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method. Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G-protein- coupled receptors and nuclear receptors. Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups. As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively. Conclusion/Significance Our results indicate that the network prediction system thus established is quite promising and encouraging. PMID:20300175

Predicting drug-target interaction for new drugs using enhanced similarity measures and super-target clustering.

PubMed

Shi, Jian-Yu; Yiu, Siu-Ming; Li, Yiming; Leung, Henry C M; Chin, Francis Y L

2015-07-15

Predicting drug-target interaction using computational approaches is an important step in drug discovery and repositioning. To predict whether there will be an interaction between a drug and a target, most existing methods identify similar drugs and targets in the database. The prediction is then made based on the known interactions of these drugs and targets. This idea is promising. However, there are two shortcomings that have not yet been addressed appropriately. Firstly, most of the methods only use 2D chemical structures and protein sequences to measure the similarity of drugs and targets respectively. However, this information may not fully capture the characteristics determining whether a drug will interact with a target. Secondly, there are very few known interactions, i.e. many interactions are "missing" in the database. Existing approaches are biased towards known interactions and have no good solutions to handle possibly missing interactions which affect the accuracy of the prediction. In this paper, we enhance the similarity measures to include non-structural (and non-sequence-based) information and introduce the concept of a "super-target" to handle the problem of possibly missing interactions. Based on evaluations on real data, we show that our similarity measure is better than the existing measures and our approach is able to achieve higher accuracy than the two best existing algorithms, WNN-GIP and KBMF2K. Our approach is available at http://web.hku.hk/∼liym1018/projects/drug/drug.html or http://www.bmlnwpu.org/us/tools/PredictingDTI_S2/METHODS.html. Copyright © 2015 Elsevier Inc. All rights reserved.

Optically Levitated Targets as a Source for High Brightness X-rays and a Platform for Mass-Limited Laser-interaction Experiments

NASA Astrophysics Data System (ADS)

Giltrap, Samuel; Stuart, Nick; Robinson, Tim; Armstrong, Chris; Hicks, George; Eardley, Sam; Gumbrell, Ed; Smith, Roland

2016-10-01

Here we report on the development of an optical levitation based x-ray and proton source, motivated by the requirement for a debris free, high spatial resolution, and low EMP source for x-ray radiography and proton production. Research at Imperial College has led to the development of a feedback controlled optical levitation trap which is capable of holding both solid (Glass beads) and liquid (silicon based oil) micro-targets ( 3-10um). The optical levitation trap has been successfully fielded in a high-intensity laser interaction experiment at Imperial College London and at the Vulcan Petawatt Laser system at the Rutherford Appleton Laboratory (RAL). Here we report on the results from that RAL run including; an x-ray source size of 10-15um with very good spherical symmetry when compared to wire targets, secondly very low EMP signal from isolated levitated targets (9 times less RF signal than a comparable wire target). At Imperial College we were also able to record an x-ray energy spectrum which produced an electron temperature of 0.48KeV, and performed interferometry of a shock evolving into a blast wave off an optically levitated droplet which allowed us to infer the electron density within the shock front.

Drug-target interaction prediction from PSSM based evolutionary information.

PubMed

Mousavian, Zaynab; Khakabimamaghani, Sahand; Kavousi, Kaveh; Masoudi-Nejad, Ali

2016-01-01

The labor-intensive and expensive experimental process of drug-target interaction prediction has motivated many researchers to focus on in silico prediction, which leads to the helpful information in supporting the experimental interaction data. Therefore, they have proposed several computational approaches for discovering new drug-target interactions. Several learning-based methods have been increasingly developed which can be categorized into two main groups: similarity-based and feature-based. In this paper, we firstly use the bi-gram features extracted from the Position Specific Scoring Matrix (PSSM) of proteins in predicting drug-target interactions. Our results demonstrate the high-confidence prediction ability of the Bigram-PSSM model in terms of several performance indicators specifically for enzymes and ion channels. Moreover, we investigate the impact of negative selection strategy on the performance of the prediction, which is not widely taken into account in the other relevant studies. This is important, as the number of non-interacting drug-target pairs are usually extremely large in comparison with the number of interacting ones in existing drug-target interaction data. An interesting observation is that different levels of performance reduction have been attained for four datasets when we change the sampling method from the random sampling to the balanced sampling. Copyright © 2015 Elsevier Inc. All rights reserved.

The Fixed Target Experiment for Studies of Baryonic Matter at the Nuclotron (BM@N)

NASA Astrophysics Data System (ADS)

Kapishin, M. N.

2017-12-01

BM@N (Baryonic Matter at Nuclotron) is the first experiment to be realized at the NICA-Nuclotron accelerator complex. The aim of the BM@N experiment is to study relativistic heavy ion beam interactions with fixed targets. The BM@N setup, results of Monte Carlo simulations, and the BM@N experimental program are presented.

Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation.

PubMed

Farhood, Bagher; Goradel, Nasser Hashemi; Mortezaee, Keywan; Khanlarkhani, Neda; Salehi, Ensieh; Nashtaei, Maryam Shabani; Shabeeb, Dheyauldeen; Musa, Ahmed Eleojo; Fallah, Hengameh; Najafi, Masoud

2018-06-17

Nowadays, using ionizing radiation (IR) is necessary for clinical, agricultural, nuclear energy or industrial applications. Accidental exposure to IR after a radiation terror or disaster poses a threat to human. In contrast to the old dogma of radiation toxicity, several experiments during the last two recent decades have revealed that intercellular signaling and communications play a key role in this procedure. Elevated level of cytokines and other intercellular signals increase oxidative damage and inflammatory responses via reduction/oxidation interactions (redox system). Intercellular signals induce production of free radicals and inflammatory mediators by some intermediate enzymes such as cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), NADPH oxidase, and also via triggering mitochondrial ROS. Furthermore, these signals facilitate cell to cell contact and increasing cell toxicity via cohort effect. Nitric oxide is a free radical with ability to act as an intercellular signal that induce DNA damage and changes in some signaling pathways in irradiated as well as non-irradiated adjacent cells. Targeting of these mediators by some anti-inflammatory agents or via antioxidants such as mitochondrial ROS scavengers opens a window to mitigate radiation toxicity after an accidental exposure. Experiments which have been done so far suggests that some cytokines such as IL-1β, TNF-α, TGF-β, IL-4 and IL-13 are some interesting targets that depend on irradiated organs and may help mitigate radiation toxicity. Moreover, animal experiments in recent years indicated that targeting of toll like receptors (TLRs) may be more useful for radioprotection and mitigation. In this review, we aimed to describe the role of intercellular interactions in oxidative injury, inflammation, cell death and killing effects of IR. Moreover, we described evidence on potential mitigation of radiation injury via targeting of these mediators.

Backscattering from targets residing in caustics resulting from ocean boundary interactions

NASA Astrophysics Data System (ADS)

Dzikowicz, Benjamin R.; Marston, Philip L.

2005-04-01

Detection of targets by backscatter in shallow water can be enhanced by interactions with ocean boundaries. A laboratory experiment is performed where a spherical target passes through an Airy caustic formed by a curved surface. When the target resides in the insonified region of the caustic there are two sets of multi-path rays: two pairs reflecting once off the surface (either to or from the target), and three reflecting twice off the surface (to and from the target). When a target moves across the caustic the singly reflected rays merge, as do the doubly reflected. With a longer tone burst the rays in each set overlap and the backscatter is greatly enhanced as the target moves into the insonified region. For a point target the singly reflected backscatter scales as an Airy function [B. R. Dzikowicz and P. L. Marston, J. Acoust. Soc. Am. 116, 2751-2757 (2004)], and the doubly reflected as the square of an Airy function. For a finite target the doubly reflected backscatter unfolds into a hyperbolic umbilic function. The arguments of the Airy and Hyperbolic Umbilic functions are calculated using the relative echo times of transient pulses. [Work supported by ONR.

Pion emission in α-particle interactions with various targets of nuclear emulsion detector

NASA Astrophysics Data System (ADS)

Abdelsalam, A.; Abou-Moussa, Z.; Rashed, N.; M. Badawy, B.; A. Amer, H.; Osman, W.; M. El-Ashmawy, M.; Abdallah, N.

2015-09-01

The behavior of relativistic hadron multiplicity for 4He-nucleus interactions is investigated. The experiment is carried out at 2.1 A and 3.7 A GeV (Dubna energy) to search for the incident energy effect on the interactions inside different emulsion target nuclei. Data are presented in terms of the number of emitted relativistic hadrons in both forward and backward angular zones. The dependence on the target size is presented. For this purpose the statistical events are discriminated into groups according to the interactions with H, CNO, Em, and AgBr target nuclei. The separation of events, into the mentioned groups, is executed based on Glauber's multiple scattering theory approach. Features suggestive of a decay mechanism seem to be a characteristic of the backward emission of relativistic hadrons. The results strongly support the assumption that the relativistic hadrons may already be emitted during the de-excitation of the excited target nucleus, in a behavior like that of compound-nucleus disintegration. Regarding the limiting fragmentation hypothesis beyond 1 A GeV, the target size is the main parameter affecting the backward production of the relativistic hadron. The incident energy is a principal factor responsible for the forward relativistic hadron production, implying that this system of particle production is a creation system. However, the target size is an effective parameter as well as the projectile size considering the geometrical concept regarded in the nuclear fireball model. The data are analyzed in the framework of the FRITIOF model.

Simulations of bremsstrahlung emission in ultra-intense laser interactions with foil targets

NASA Astrophysics Data System (ADS)

Vyskočil, Jiří; Klimo, Ondřej; Weber, Stefan

2018-05-01

Bremsstrahlung emission from interactions of short ultra-intense laser pulses with solid foils is studied using particle-in-cell (PIC) simulations. A module for simulating bremsstrahlung has been implemented in the PIC loop to self-consistently account for the dynamics of the laser–plasma interaction, plasma expansion, and the emission of gamma ray photons. This module made it possible to study emission from thin targets, where refluxing of hot electrons plays an important role. It is shown that the angular distribution of the emitted photons exhibits a four-directional structure with the angle of emission decreasing with the increase of the width of the target. Additionally, a collimated forward flash consisting of high energy photons has been identified in thin targets. The conversion efficiency of the energy of the laser pulse to the energy of the gamma rays rises with both the driving pulse intensity, and the thickness of the target. The amount of gamma rays also increases with the atomic number of the target material, despite a lower absorption of the driving laser pulse. The angular spectrum of the emitted gamma rays is directly related to the increase of hot electron divergence during their refluxing and its measurement can be used in experiments to study this process.

First Experiments with the Polarized Internal Gas Target (PIT) at ANKE/COSY

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

Engels, R.; Lorentz, B.; Prasuhn, D.

2008-02-06

For future few-nucleon interaction studies with polarized beams and targets at COSY-Juelich, a polarized internal storage-cell gas target was implemented at the magnet spectrometer ANKE in summer 2005. First commissioning of the polarized Atomic Beam Source (ABS) at ANKE was carried out and some improvements of the system have been done. Storage-cell tests to determine the COSY beam dimensions have been performed. Electron cooling combined with stacking and stochastic cooling have been studied. Experiments with N{sub 2} gas in the storage cell to simulate the background produced by beam interaction with the aluminum cell walls were performed to investigate themore » beam heating by the target gas. The analysis of the d-vector p-vector {yields}dp and d-vector p-vector{yields}(dp{sub sp}){pi}{sup 0} reactions showed that events from the extended target can be clearly identified in the ANKE detector system.The polarization of the atomic beam of the ABS, positioned close to the strong dipole magnet D2 of ANKE, was tuned with a Lamb-shift polarimeter (LSP) beneath the target chamber. With use of the known analyzing powers of the quasi-free np{yields}d{pi}{sup 0} reaction, the polarization in the storage cell was measured to be Q{sub y} = 0.79{+-}0.07 in the vertical stray field of the D2 magnet acting as a holding field. The achieved target thickness was 2x10{sup 13} atoms/cm{sup 2} for one hyperfine state populated in the ABS beam only. With a COSY beam intensity of 6x10{sup 9} stored polarized deuterons in the ring, the luminosity for double polarized experiments was 1x10{sup 29} cm{sup -2} s{sup -1}.« less

First Experiments with the Polarized Internal Gas Target (PIT) at ANKE/COSY

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

Engels, R.; Lorentz, B.; Prasuhn, D.

2009-08-04

For future few-nucleon interaction studies with polarized beams and targets at COSY-Juelich, a polarized internal storage-cell gas target was implemented at the magnet spectrometer ANKE. First commissioning of the polarized Atomic Beam Source (ABS) at ANKE was carried out and some improvements of the system have been done. Storage-cell tests to determine the COSY beam dimensions have been performed. Electron cooling combined with stacking and stochastic cooling have been studied. Experiments with N{sub 2} gas in the storage cell to simulate the background produced by beam interaction with the aluminum cell walls were performed to investigate the beam heating bymore » the target gas. The analysis of the d-vectorp-vector->dp and d-vectorp-vector->(dp{sub sp})pi{sup 0} reactions showed that events from different positions of the extended target can be clearly identified in the ANKE detector system. The polarization of the atomic beam of the ABS, positioned close to the strong dipole magnet D2 of ANKE, was tuned with a Lamb-shift polarimeter (LSP) beneath the target chamber. With use of the known analyzing powers of the quasi-free np->dpi{sup 0} reaction, the polarization in the storage cell was measured to be Q{sub y} = 0.79+-0.07 in the vertical stray field of the D2 magnet acting as a holding field. The target thickness achieved was 2x10{sup 13} atoms/cm{sup 2} for one hyperfine state populated in the ABS beam only. With a COSY beam intensity of 6x10{sup 9} stored polarized deuterons in the ring, the luminosity for double polarized experiments was 1x10{sup 29} cm{sup -2} s{sup -1}.« less

Measurement of the target current by inductive probe during laser interaction on terawatt laser system PALS.

PubMed

Cikhardt, J; Krása, J; De Marco, M; Pfeifer, M; Velyhan, A; Krouský, E; Cikhardtová, B; Klír, D; Rezáč, K; Ullschmied, J; Skála, J; Kubeš, P; Kravárik, J

2014-10-01

Measurements of the return-current flowing through a solid target irradiated with the sub-nanosecond kJ-class Prague Asterix Laser System is reported. A new inductive target probe was developed which allows us measuring the target current derivative in a kA/ns range. The dependences of the target current on the laser pulse energy for cooper, graphite, and polyethylene targets are reported. The experiment shows that the target current is proportional to the deposited laser energy and is strongly affected by the shot-to-shot fluctuations. The corresponding maximum target charge exceeded a value of 10 μC. A return-current dependence of the electromagnetic pulse produced by the laser-target interaction is presented.

Comprehensive peptidomimetic libraries targeting protein-protein interactions.

PubMed

Whitby, Landon R; Boger, Dale L

2012-10-16

Transient protein-protein interactions (PPIs) are essential components in cellular signaling pathways as well as in important processes such as viral infection, replication, and immune suppression. The unknown or uncharacterized PPIs involved in such interaction networks often represent compelling therapeutic targets for drug discovery. To date, however, the main strategies for discovery of small molecule modulators of PPIs are typically limited to structurally characterized targets. Recent developments in molecular scaffolds that mimic the side chain display of peptide secondary structures have yielded effective designs, but few screening libraries of such mimetics are available to interrogate PPI targets. We initiated a program to prepare a comprehensive small molecule library designed to mimic the three major recognition motifs that mediate PPIs (α-helix, β-turn, and β-strand). Three libraries would be built around templates designed to mimic each such secondary structure and substituted with all triplet combinations of groups representing the 20 natural amino acid side chains. When combined, the three libraries would contain a member capable of mimicking the key interaction and recognition residues of most targetable PPIs. In this Account, we summarize the results of the design, synthesis, and validation of an 8000 member α-helix mimetic library and a 4200 member β-turn mimetic library. We expect that the screening of these libraries will not only provide lead structures against α-helix- or β-turn-mediated protein-protein or peptide-receptor interactions, even if the nature of the interaction is unknown, but also yield key insights into the recognition motif (α-helix or β-turn) and identify the key residues mediating the interaction. Consistent with this expectation, the screening of the libraries against p53/MDM2 and HIV-1 gp41 (α-helix mimetic library) or the opioid receptors (β-turn mimetic library) led to the discovery of library members expected

The first target experiments on the National Ignition Facility

NASA Astrophysics Data System (ADS)

Landen, O. L.; Glenzer, S. H.; Froula, D. H.; Dewald, E. L.; Suter, L. J.; Schneider, M. B.; Hinkel, D. E.; Fernandez, J. C.; Kline, J. L.; Goldman, S. R.; Braun, D. G.; Celliers, P. M.; Moon, S. J.; Robey, H. S.; Lanier, N. E.; Glendinning, S. G.; Blue, B. E.; Wilde, B. H.; Jones, O. S.; Schein, J.; Divol, L.; Kalantar, D. H.; Campbell, K. M.; Holder, J. P.; McDonald, J. W.; Niemann, C.; MacKinnon, A. J.; Collins, G. W.; Bradley, D. K.; Eggert, J. H.; Hicks, D. G.; Gregori, G.; Kirkwood, R. K.; Young, B. K.; Foster, J. M.; Hansen, J. F.; Perry, T. S.; Munro, D. H.; Baldis, H. A.; Grim, G. P.; Heeter, R. F.; Hegelich, M. B.; Montgomery, D. S.; Rochau, G. A.; Olson, R. E.; Turner, R. E.; Workman, J. B.; Berger, R. L.; Cohen, B. I.; Kruer, W. L.; Langdon, A. B.; Langer, S. H.; Meezan, N. B.; Rose, H. A.; Still, C. H.; Williams, E. A.; Dodd, E. S.; Edwards, M. J.; Monteil, M.-C.; Stevenson, R. M.; Thomas, B. R.; Coker, R. F.; Magelssen, G. R.; Rosen, P. A.; Stry, P. E.; Woods, D.; Weber, S. V.; Young, P. E.; Alvarez, S.; Armstrong, G.; Bahr, R.; Bourgade, J.-L.; Bower, D.; Celeste, J.; Chrisp, M.; Compton, S.; Cox, J.; Constantin, C.; Costa, R.; Duncan, J.; Ellis, A.; Emig, J.; Gautier, C.; Greenwood, A.; Griffith, R.; Holdner, F.; Holtmeier, G.; Hargrove, D.; James, T.; Kamperschroer, J.; Kimbrough, J.; Landon, M.; Lee, F. D.; Malone, R.; May, M.; Montelongo, S.; Moody, J.; Ng, E.; Nikitin, A.; Pellinen, D.; Piston, K.; Poole, M.; Rekow, V.; Rhodes, M.; Shepherd, R.; Shiromizu, S.; Voloshin, D.; Warrick, A.; Watts, P.; Weber, F.; Young, P.; Arnold, P.; Atherton, L.; Bardsley, G.; Bonanno, R.; Borger, T.; Bowers, M.; Bryant, R.; Buckman, S.; Burkhart, S.; Cooper, F.; Dixit, S. N.; Erbert, G.; Eder, D. C.; Ehrlich, R. E.; Felker, B.; Fornes, J.; Frieders, G.; Gardner, S.; Gates, C.; Gonzalez, M.; Grace, S.; Hall, T.; Haynam, C. A.; Heestand, G.; Henesian, M. A.; Hermann, M.; Hermes, G.; Huber, S.; Jancaitis, K.; Johnson, S.; Kauffman, B.; Kelleher, T.; Kohut, T.; Koniges, A. E.; Labiak, T.; Latray, D.; Lee, A.; Lund, D.; Mahavandi, S.; Manes, K. R.; Marshall, C.; McBride, J.; McCarville, T.; McGrew, L.; Menapace, J.; Mertens, E.; Murray, J.; Neumann, J.; Newton, M.; Opsahl, P.; Padilla, E.; Parham, T.; Parrish, G.; Petty, C.; Polk, M.; Powell, C.; Reinbachs, I.; Rinnert, R.; Riordan, B.; Ross, G.; Robert, V.; Tobin, M.; Sailors, S.; Saunders, R.; Schmitt, M.; Shaw, M.; Singh, M.; Spaeth, M.; Stephens, A.; Tietbohl, G.; Tuck, J.; van Wonterghem, B. M.; Vidal, R.; Wegner, P. J.; Whitman, P.; Williams, K.; Winward, K.; Work, K.; Wallace, R.; Nobile, A.; Bono, M.; Day, B.; Elliott, J.; Hatch, D.; Louis, H.; Manzenares, R.; O'Brien, D.; Papin, P.; Pierce, T.; Rivera, G.; Ruppe, J.; Sandoval, D.; Schmidt, D.; Valdez, L.; Zapata, K.; MacGowan, B. J.; Eckart, M. J.; Hsing, W. W.; Springer, P. T.; Hammel, B. A.; Moses, E. I.; Miller, G. H.

2007-08-01

A first set of shock timing, laser-plasma interaction, hohlraum energetics and hydrodynamic experiments have been performed using the first 4 beams of the National Ignition Facility (NIF), in support of indirect drive Inertial Confinement Fusion (ICF) and High Energy Density Physics (HEDP). In parallel, a robust set of optical and X-ray spectrometers, interferometer, calorimeters and imagers have been activated. The experiments have been undertaken with laser powers and energies of up to 8 TW and 17 kJ in flattop and shaped 1 9 ns pulses focused with various beam smoothing options. The experiments have demonstrated excellent agreement between measured and predicted laser-target coupling in foils and hohlraums, even when extended to a longer pulse regime unattainable at previous laser facilities, validated the predicted effects of beam smoothing on intense laser beam propagation in long scale-length plasmas and begun to test 3D codes by extending the study of laser driven hydrodynamic jets to 3D geometries.

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

PubMed

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

NASA Astrophysics Data System (ADS)

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

Forming Uniform Deuterium-Ice Layers in Cryogenic Targets: Experiences Using the OMEGA Cryogenic Target Handling System

NASA Astrophysics Data System (ADS)

Harding, D. R.; Wittman, M. D.; Elasky, L.; Iwan, L. S.; Lund, L.

2001-10-01

The OMEGA Cryogenic Target Handling System (OCTHS) allows variable-thickness ice layers (nominal 100-μm) to be formed inside OMEGA-size (1-mm-diam., 3-μm-wall) plastic shells. The OCTHS design provides the most straightforward thermal environment for layering targets: permeation filled spherical targets are in a spherical isothermal environment. The layered target can be rotated 360^o to acquire multiple views of the ice layer. However, the capability of providing cryogenic targets for implosion experiments imposes constraints that do not exist in test systems dedicated to ice-layering studies. Most affected is the ability to characterize the target: space constraints and the need for multiple sets of windows limit the viewing access to f/5 optics, which affects the image quality. With these features, the OCTS provides the most relevant test system, to date, for layering targets and quantifying the overall ice roughness. No single layering protocol provides repeatable ice smoothness. All techniques require extensive operator interaction, and the layering process is lengthy. Typical ice rms smoothness varied from 5 to 10 μm for all targets studied. Characterizing the ice layer from different views shows a ~30% variation in the ice rms smoothness and a greater difference in the power spectra, depending on the view axis. This work was supported by the U.S. DOE Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460.

Design of an Experiment to Observe Laser-Plasma Interactions on NIKE

NASA Astrophysics Data System (ADS)

Phillips, L.; Weaver, J.; Manheimer, W.; Zalesak, S.; Schmitt, A.; Fyfe, D.; Afeyan, B.; Charbonneau-Lefort, M.

2007-11-01

Recent proposed designs (Obenschain et al., Phys. Plasmas 13 056320 (2006)) for direct-drive ICF targets for energy applications involve high implosion velocities combined with higher laser irradiances. The use of high irradiances increases the likelihood of deleterious laser plasma instabilities (LPI) that may lead, for example, to the generation of fast electrons. The proposed use of a 248 nm KrF laser to drive these targets is expected to minimize LPI; this is being studied by experiments at NRL's NIKE facility. We used a modification of the FAST code that models laser pulses with arbitrary spatial and temporal profiles to assist in designing these experiments. The goal is to design targets and pulseshapes to create plasma conditions that will produce sufficient growth of LPI to be observable on NIKE. Using, for example, a cryogenic DT target that is heated by a brief pulse and allowed to expand freely before interacting with a second, high-intensity pulse, allows the development of long scalelengths at low electron temperatures and leads to a predicted 20-efold growth in two-plasmon amplitude.

Two-Plasmon Decay Mitigation in Direct-Drive Inertial-Confinement-Fusion Experiments Using Multilayer Targets.

PubMed

Follett, R K; Delettrez, J A; Edgell, D H; Goncharov, V N; Henchen, R J; Katz, J; Michel, D T; Myatt, J F; Shaw, J; Solodov, A A; Stoeckl, C; Yaakobi, B; Froula, D H

2016-04-15

Multilayer direct-drive inertial-confinement-fusion targets are shown to significantly reduce two-plasmon decay (TPD) driven hot-electron production while maintaining high hydrodynamic efficiency. Implosion experiments on the OMEGA laser used targets with silicon layered between an inner beryllium and outer silicon-doped plastic ablator. A factor-of-5 reduction in hot-electron generation (>50  keV) was observed in the multilayer targets relative to pure CH targets. Three-dimensional simulations of the TPD-driven hot-electron production using a laser-plasma interaction code (lpse) that includes nonlinear and kinetic effects show good agreement with the measurements. The simulations suggest that the reduction in hot-electron production observed in the multilayer targets is primarily caused by increased electron-ion collisional damping.

Optimizing prognosis-related key miRNA-target interactions responsible for cancer metastasis.

PubMed

Zhao, Hongying; Yuan, Huating; Hu, Jing; Xu, Chaohan; Liao, Gaoming; Yin, Wenkang; Xu, Liwen; Wang, Li; Zhang, Xinxin; Shi, Aiai; Li, Jing; Xiao, Yun

2017-12-12

Increasing evidence suggests that the abnormality of microRNAs (miRNAs) and their downstream targets is frequently implicated in the pathogenesis of human cancers, however, the clinical benefit of causal miRNA-target interactions has been seldom studied. Here, we proposed a computational method to optimize prognosis-related key miRNA-target interactions by combining transcriptome and clinical data from thousands of TCGA tumors across 16 cancer types. We obtained a total of 1,956 prognosis-related key miRNA-target interactions between 112 miRNAs and 1,443 their targets. Interestingly, these key target genes are specifically involved in tumor progression-related functions, such as 'cell adhesion' and 'cell migration'. Furthermore, they are most significantly correlated with 'tissue invasion and metastasis', a hallmark of metastasis, in ten distinct types of cancer through the hallmark analysis. These results implicated that the prognosis-related key miRNA-target interactions were highly associated with cancer metastasis. Finally, we observed that the combination of these key miRNA-target interactions allowed to distinguish patients with good prognosis from those with poor prognosis both in most TCGA cancer types and independent validation sets, highlighting their roles in cancer metastasis. We provided a user-friendly database named miRNATarget (freely available at http://biocc.hrbmu.edu.cn/miRNATar/), which provides an overview of the prognosis-related key miRNA-target interactions across 16 cancer types.

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

PubMed

Rosell, Mireia; Fernández-Recio, Juan

2018-04-01

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

A diamond active target for the PADME experiment

NASA Astrophysics Data System (ADS)

Chiodini, G.

2017-02-01

The PADME (Positron Annihilation into Dark Mediator Experiment) collaboration searches for dark photons produced in the annihilation e++e-→γ+A' of accelerated positrons with atomic electrons of a fixed target at the Beam Test Facility of Laboratori Nazionali di Frascati. The apparatus can detect dark photons decaying into visible A'→e+e- and invisible A'→χχ channels, where χ's are particles of a secluded sector weakly interacting and therefore undetected. In order to improve the missing mass resolution and to measure the beam flux, PADME has an active target able to reconstruct the beam spot position and the bunch multiplicity. In this work the active target is described, which is made of a detector grade polycrystalline synthetic diamond with strip electrodes on both surfaces. The electrodes segmentation allows to measure the beam profile along X and Y and evaluate the average beam position bunch per bunch. The results of beam tests for the first two diamond detector prototypes are shown. One of them holds innovative graphitic electrodes built with a custom process developed in the laboratory, and the other one with commercially available traditional Cr-Au electrodes. The front-end electronics used in the test beam is discussed and the performance observed is presented. Finally, the final design of the target to be realized at the beginning of 2017 to be ready for data taking in 2018 is illustrated.

Two-plasmon decay mitigation in direct-drive inertial-confinement-fusion experiments using multilayer targets

DOE PAGES

Follett, R. K.; Delettrez, J. A.; Edgell, D. H.; ...

2016-04-15

Multilayer direct-drive inertial-confinement-fusion (ICF) targets are shown to significantly reduce two-plasmon-decay (TPD) driven hot-electron production while maintaining high hydrodynamic efficiency. Implosion experiments on the OMEGA Laser used targets with silicon layered between an inner beryllium and outer silicon-doped plastic ablator. A factor of five reduction in hot-electron generation (> 50 keV) was observed in the multilayer targets relative to pure CH targets. Three-dimensional simulations of the TPD driven hot-electron production using a laser-plasma interaction code (LPSE) that includes nonlinear and kinetic effects show excellent agreement with the measurements. As a result, the simulations suggest that the reduction in hot-electron productionmore » observed in the multilayer targets is primarily due to increased electron-ion collisional damping.« less

Nanoparticle-blood interactions: the implications on solid tumour targeting.

PubMed

Lazarovits, James; Chen, Yih Yang; Sykes, Edward A; Chan, Warren C W

2015-02-18

Nanoparticles are suitable platforms for cancer targeting and diagnostic applications. Typically, less than 10% of all systemically administered nanoparticles accumulate in the tumour. Here we explore the interactions of blood components with nanoparticles and describe how these interactions influence solid tumour targeting. In the blood, serum proteins adsorb onto nanoparticles to form a protein corona in a manner dependent on nanoparticle physicochemical properties. These serum proteins can block nanoparticle tumour targeting ligands from binding to tumour cell receptors. Additionally, serum proteins can also encourage nanoparticle uptake by macrophages, which decreases nanoparticle availability in the blood and limits tumour accumulation. The formation of this protein corona will also increase the nanoparticle hydrodynamic size or induce aggregation, which makes nanoparticles too large to enter into the tumour through pores of the leaky vessels, and prevents their deep penetration into tumours for cell targeting. Recent studies have focused on developing new chemical strategies to reduce or eliminate serum protein adsorption, and rescue the targeting potential of nanoparticles to tumour cells. An in-depth and complete understanding of nanoparticle-blood interactions is key to designing nanoparticles with optimal physicochemical properties with high tumour accumulation. The purpose of this review article is to describe how the protein corona alters the targeting of nanoparticles to solid tumours and explains current solutions to solve this problem.

Secondary neutron-production cross sections from heavy-ion interactions in composite targets

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

Heilbronn, L.; Iwata, Y.; Murakami, T.

Secondary neutron-production cross sections have been measured from interactions of 290 MeV/nucleon C and 600 MeV/nucleon Ne in a target composed of simulated Martian regolith and polyethylene, and from 400 MeV/nucleon Ne interactions in wall material from the International Space Station. The data were measured between 5 deg. and 80 deg. in the laboratory. We report the double-differential cross sections, angular distributions, and total neutron-production cross sections from all three systems. The spectra from all three systems exhibit behavior previously reported in other heavy-ion neutron-production experiments, namely, a peak at forward angles near the energy corresponding to the beam velocity,more » with the remaining spectra generated by pre-equilibrium and equilibrium processes. The double-differential cross sections are fitted with a moving-source parametrization. Also reported are the data without corrections for neutron flux attenuation in the target and other intervening materials and for neutron production in nontarget materials near the target position. These uncorrected spectra are compared with SHIELD-HIT and PHITS transport model calculations. The transport model calculations reproduce the spectral shapes well but, on average, underestimate the magnitudes of the cross sections.« less

Interactive target tracking for persistent wide-area surveillance

NASA Astrophysics Data System (ADS)

Ersoy, Ilker; Palaniappan, Kannappan; Seetharaman, Guna S.; Rao, Raghuveer M.

2012-06-01

Persistent aerial surveillance is an emerging technology that can provide continuous, wide-area coverage from an aircraft-based multiple-camera system. Tracking targets in these data sets is challenging for vision algorithms due to large data (several terabytes), very low frame rate, changing viewpoint, strong parallax and other imperfections due to registration and projection. Providing an interactive system for automated target tracking also has additional challenges that require online algorithms that are seamlessly integrated with interactive visualization tools to assist the user. We developed an algorithm that overcomes these challenges and demonstrated it on data obtained from a wide-area imaging platform.

Target-projectile interaction during impact melting at Kamil Crater, Egypt

NASA Astrophysics Data System (ADS)

Fazio, Agnese; D'Orazio, Massimo; Cordier, Carole; Folco, Luigi

2016-05-01

In small meteorite impacts, the projectile may survive through fragmentation; in addition, it may melt, and chemically and physically interact with both shocked and melted target rocks. However, the mixing/mingling between projectile and target melts is a process still not completely understood. Kamil Crater (45 m in diameter; Egypt), generated by the hypervelocity impact of the Gebel Kamil Ni-rich ataxite on sandstone target, allows to study the target-projectile interaction in a simple and fresh geological setting. We conducted a petrographic and geochemical study of macroscopic impact melt lapilli and bombs ejected from the crater, which were collected during our geophysical campaign in February 2010. Two types of glasses constitute the impact melt lapilli and bombs: a white glass and a dark glass. The white glass is mostly made of SiO2 and it is devoid of inclusions. Its negligible Ni and Co contents suggest derivation from the target rocks without interaction with the projectile (<0.1 wt% of projectile contamination). The dark glass is a silicate melt with variable contents of Al2O3 (0.84-18.7 wt%), FeOT (1.83-61.5 wt%), and NiO (<0.01-10.2 wt%). The dark glass typically includes fragments (from few μm to several mm in size) of shocked sandstone, diaplectic glass, lechatelierite, and Ni-Fe metal blebs. The metal blebs are enriched in Ni compared to the Gebel Kamil meteorite. The dark glass is thus a mixture of target and projectile melts (11-12 wt% of projectile contamination). Based on recently proposed models for target-projectile interaction and for impact glass formation, we suggest a scenario for the glass formation at Kamil. During the transition from the contact and compression stage and the excavation stage, projectile and target liquids formed at their interface and chemically interact in a restricted zone. Projectile contamination affected only a shallow portion of the target rocks. The SiO2 melt that eventually solidified as white glass behaved as

Strong electromagnetic pulses generated in high-intensity short-pulse laser interactions with thin foil targets

NASA Astrophysics Data System (ADS)

Rączka, P.; Dubois, J.-L.; Hulin, S.; Tikhonchuk, V.; Rosiński, M.; Zaraś-Szydłowska, A.; Badziak, J.

2017-12-01

Measurements are reported of the target neutralization current, the target charge, and the tangential component of the magnetic field generated as a result of laser-target interaction by pulses with the energy in the range of 45 mJ to 92 mJ on target and the pulse duration from 39 fs to 1000 fs. The experiment was performed at the Eclipse facility in CELIA, Bordeaux. The aim of the experiment was to extend investigations performed for the thick (mm scale) targets to the case of thin (micrometer thickness) targets in a way that would allow for a straightforward comparison of the results. We found that thin foil targets tend to generate 20 to 50 percent higher neutralization current and the target charge than the thick targets. The measurement of the tangential component of the magnetic field had shown that the initial spike is dominated by the 1 ns pulse consistent with the 1 ns pulse of the neutralization current, but there are some differences between targets of different type on sub-ns scale, which is an effect going beyond a simple picture of the target acting as an antenna. The sub-ns structure appears to be reproducible to surprising degree. We found that there is in general a linear correlation between the maximum value of the magnetic field and the maximum neutralization current, which supports the target-antenna picture, except for pulses hundreds of fs long.

A Systematic Prediction of Drug-Target Interactions Using Molecular Fingerprints and Protein Sequences.

PubMed

Huang, Yu-An; You, Zhu-Hong; Chen, Xing

2018-01-01

Drug-Target Interactions (DTI) play a crucial role in discovering new drug candidates and finding new proteins to target for drug development. Although the number of detected DTI obtained by high-throughput techniques has been increasing, the number of known DTI is still limited. On the other hand, the experimental methods for detecting the interactions among drugs and proteins are costly and inefficient. Therefore, computational approaches for predicting DTI are drawing increasing attention in recent years. In this paper, we report a novel computational model for predicting the DTI using extremely randomized trees model and protein amino acids information. More specifically, the protein sequence is represented as a Pseudo Substitution Matrix Representation (Pseudo-SMR) descriptor in which the influence of biological evolutionary information is retained. For the representation of drug molecules, a novel fingerprint feature vector is utilized to describe its substructure information. Then the DTI pair is characterized by concatenating the two vector spaces of protein sequence and drug substructure. Finally, the proposed method is explored for predicting the DTI on four benchmark datasets: Enzyme, Ion Channel, GPCRs and Nuclear Receptor. The experimental results demonstrate that this method achieves promising prediction accuracies of 89.85%, 87.87%, 82.99% and 81.67%, respectively. For further evaluation, we compared the performance of Extremely Randomized Trees model with that of the state-of-the-art Support Vector Machine classifier. And we also compared the proposed model with existing computational models, and confirmed 15 potential drug-target interactions by looking for existing databases. The experiment results show that the proposed method is feasible and promising for predicting drug-target interactions for new drug candidate screening based on sizeable features. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Visualization and Analysis of MiRNA-Targets Interactions Networks.

PubMed

León, Luis E; Calligaris, Sebastián D

2017-01-01

MicroRNAs are a class of small, noncoding RNA molecules of 21-25 nucleotides in length that regulate the gene expression by base-pairing with the target mRNAs, mainly leading to down-regulation or repression of the target genes. MicroRNAs are involved in diverse regulatory pathways in normal and pathological conditions. In this context, it is highly important to identify the targets of specific microRNA in order to understand the mechanism of its regulation and consequently its involvement in disease. However, the microRNA target identification is experimentally laborious and time-consuming. The in silico prediction of microRNA targets is an extremely useful approach because you can identify potential mRNA targets, reduce the number of possibilities and then, validate a few microRNA-mRNA interactions in an in vitro experimental model. In this chapter, we describe, in a simple way, bioinformatics guidelines to use miRWalk database and Cytoscape software for analyzing microRNA-mRNA interactions through their visualization as a network.

LH2 Target Design & Position Survey Techniques for the MUSE experiment for Precise Proton Radius Measurement

NASA Astrophysics Data System (ADS)

Le Pottier, Luc; Roy, Pryiashee; Lorenzon, Wolfgang; Raymond, Richard; Steinberg, Noah; Rossi de La Fuente, Erick; MUSE (MUon proton Scattering Experiment) Collaboration

2017-09-01

The proton radius puzzle is a currently unresolved problem which has intrigued the scientific community, dealing with a 7 σ discrepancy between the proton radii determined from muonic hydrogen spectroscopy and electron scattering measurements. The MUon Scattering Experiment (MUSE) aims to resolve this puzzle by performing the first simultaneous elastic scattering measurements of both electrons and muons on the proton, which will allow the comparison of the radii from the two interactions with reduced systematic uncertainties. The data from this experiment is expected to provide the best test of lepton universality to date. The experiment will take place at the Paul Scherrer Institute in Switzerland in 2018. An essential component of the experiment is a liquid hydrogen (LH2) cryotarget system. Our group at the University of Michigan is responsible for the design, fabrication and installation of this system. Here we present our LH2 target cell design and fabrication techniques for successful operation at 20 K and 1 atm, and our computer vision-based target position survey system which will determine the position of the target, installed inside a vacuum chamber, with 0.01 mm or better precision at the height of the liquid hydrogen target and along the beam direction during the experiment.

SELF-BLM: Prediction of drug-target interactions via self-training SVM.

PubMed

Keum, Jongsoo; Nam, Hojung

2017-01-01

Predicting drug-target interactions is important for the development of novel drugs and the repositioning of drugs. To predict such interactions, there are a number of methods based on drug and target protein similarity. Although these methods, such as the bipartite local model (BLM), show promise, they often categorize unknown interactions as negative interaction. Therefore, these methods are not ideal for finding potential drug-target interactions that have not yet been validated as positive interactions. Thus, here we propose a method that integrates machine learning techniques, such as self-training support vector machine (SVM) and BLM, to develop a self-training bipartite local model (SELF-BLM) that facilitates the identification of potential interactions. The method first categorizes unlabeled interactions and negative interactions among unknown interactions using a clustering method. Then, using the BLM method and self-training SVM, the unlabeled interactions are self-trained and final local classification models are constructed. When applied to four classes of proteins that include enzymes, G-protein coupled receptors (GPCRs), ion channels, and nuclear receptors, SELF-BLM showed the best performance for predicting not only known interactions but also potential interactions in three protein classes compare to other related studies. The implemented software and supporting data are available at https://github.com/GIST-CSBL/SELF-BLM.

Relativistic-electron-beam/target interaction in plasma channels

NASA Astrophysics Data System (ADS)

Halbleib, J. A., Sr.; Wright, T. P.

1980-08-01

A model describing the transport of relativistic electron beams in plasma channels and their subsequent interaction with solid targets is developed and applied to single-beam and multiple-beam configurations. For single beams the targets consist of planar tantalum foils and, in some cases, cusp fields on the transmission side of the foils are employed to improve beam/target coupling efficiency. In the multi-beam configurations, several beams are arranged in wagon-wheel fashion so as to converge upon cylindrical targets, consisting of either hollow tantalum or solid graphite cylinders, located at the hub. For 0.3-cm beam radii that are less than or equal to the channel radii, mean specific power depositions up to about 17 TW/g per MA of injected beam current are obtained for single beams; 12-beam results are typically an order-of-magnitude less. The corresponding enhancements are up to five times the collisional stopping power for either single or multiple beams. Substantial improvement is predicted for the multi-beam interaction should future channel technology permit transport at higher current densities in smaller channels.

Effects of target heating on experiments using Kα and Kβ diagnostics.

PubMed

Palmeri, P; Boutoux, G; Batani, D; Quinet, P

2015-09-01

We describe the impact of heating and ionization on emission from the target of Kα and Kβ radiation induced by the propagation of hot electrons generated by laser-matter interaction. We consider copper as a test case and, starting from basic principles, we calculate the changes in emission wavelength, ionization cross section, and fluorescence yield as Cu is progressively ionized. We have finally considered the more realistic case when hot electrons have a distribution of energies with average energies of 50 and 500 keV (representative respectively of "shock ignition" and of "fast ignition" experiments) and in which the ions are distributed according to ionization equilibrium. In addition, by confronting our theoretical calculations with existing data, we demonstrate that this study offers a generic theoretical background for temperature diagnostics in laser-plasma interactions.

Splitter target for controlling magnetic reconnection in relativistic laser plasma interactions

NASA Astrophysics Data System (ADS)

Gu, Y. J.; Bulanov, S. S.; Korn, G.; Bulanov, S. V.

2018-04-01

The utilization of a conical target irradiated by a high power laser is proposed to study fast magnetic reconnection in relativistic plasma interactions. Such target, placed in front of the near critical density gas jet, splits the laser pulse, forming two parallel laser pulses in the 2D case and a donut shaped pulse in the 3D case. The magnetic annihilation and reconnection occur in the density downramp region of the subsequent gas jet. The magnetic field energy is converted into the particle kinetic energy. As a result, a backward accelerated electron beam is obtained as a signature of reconnection. The above mechanisms are demonstrated using particle-in-cell simulations in both 2D and 3D cases. Facilitating the synchronization of two laser beams, the proposed approach can be used in designing the corresponding experiments on studying fundamental problems of relativistic plasma physics.

Identification of chemogenomic features from drug–target interaction networks using interpretable classifiers

PubMed Central

Tabei, Yasuo; Pauwels, Edouard; Stoven, Véronique; Takemoto, Kazuhiro; Yamanishi, Yoshihiro

2012-01-01

Motivation: Drug effects are mainly caused by the interactions between drug molecules and their target proteins including primary targets and off-targets. Identification of the molecular mechanisms behind overall drug–target interactions is crucial in the drug design process. Results: We develop a classifier-based approach to identify chemogenomic features (the underlying associations between drug chemical substructures and protein domains) that are involved in drug–target interaction networks. We propose a novel algorithm for extracting informative chemogenomic features by using L1 regularized classifiers over the tensor product space of possible drug–target pairs. It is shown that the proposed method can extract a very limited number of chemogenomic features without loosing the performance of predicting drug–target interactions and the extracted features are biologically meaningful. The extracted substructure–domain association network enables us to suggest ligand chemical fragments specific for each protein domain and ligand core substructures important for a wide range of protein families. Availability: Softwares are available at the supplemental website. Contact: yamanishi@bioreg.kyushu-u.ac.jp Supplementary Information: Datasets and all results are available at http://cbio.ensmp.fr/~yyamanishi/l1binary/ . PMID:22962471

Cryogenic Target-Implosion Experiments on OMEGA

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

Harding, D.R.; Meyerhofer, D.D.; Sangster, T.C.

The University of Rochester’s Laboratory for Laser Energetics has been imploding thick cryogenic targets for six years. Improvements in the Cryogenic Target Handling System and the ability to accurately design laser pulse shapes that properly time shocks and minimize electron preheat, produced high fuel areal densities in deuterium cryogenic targets (202+/-7 mg/cm^2). The areal density was inferred from the energy loss of secondary protons in the fuel (D2) shell. Targets were driven on a low final adiabat (alpha = 2) employing techniques to radially grade the adiabat (the highest adiabat at the ablation surface). The ice layer meets the target-designmore » toughness specification for DT ice of 1-um rms (all modes), while D2 ice layers average 3.0-um-rms roughness. The implosion experiments and the improvements in the quality and understanding of cryogenic targets are presented.« less

Debiasing affective forecasting errors with targeted, but not representative, experience narratives.

PubMed

Shaffer, Victoria A; Focella, Elizabeth S; Scherer, Laura D; Zikmund-Fisher, Brian J

2016-10-01

To determine whether representative experience narratives (describing a range of possible experiences) or targeted experience narratives (targeting the direction of forecasting bias) can reduce affective forecasting errors, or errors in predictions of experiences. In Study 1, participants (N=366) were surveyed about their experiences with 10 common medical events. Those who had never experienced the event provided ratings of predicted discomfort and those who had experienced the event provided ratings of actual discomfort. Participants making predictions were randomly assigned to either the representative experience narrative condition or the control condition in which they made predictions without reading narratives. In Study 2, participants (N=196) were again surveyed about their experiences with these 10 medical events, but participants making predictions were randomly assigned to either the targeted experience narrative condition or the control condition. Affective forecasting errors were observed in both studies. These forecasting errors were reduced with the use of targeted experience narratives (Study 2) but not representative experience narratives (Study 1). Targeted, but not representative, narratives improved the accuracy of predicted discomfort. Public collections of patient experiences should favor stories that target affective forecasting biases over stories representing the range of possible experiences. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evolution of Gas Cell Targets for Magnetized Liner Inertial Fusion Experiments at the Sandia National Laboratories PECOS Test Facility

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

Paguio, R. R.; Smith, G. E.; Taylor, J. L.

Z-Beamlet (ZBL) experiments conducted at the PECOS test facility at Sandia National Laboratories (SNL) investigated the nonlinear processes in laser plasma interaction (or laserplasma instabilities LPI) that complicate the deposition of laser energy by enhanced absorption, backscatter, filamentation and beam-spray that can occur in large-scale laser-heated gas cell targets. These targets and experiments were designed to provide better insight into the physics of the laser preheat stage of the Magnetized Liner Inertial Fusion (MagLIF) scheme being tested on the SNL Z-machine. The experiments aim to understand the tradeoffs between laser spot size, laser pulse shape, laser entrance hole (LEH) windowmore » thickness, and fuel density for laser preheat. Gas cell target design evolution and fabrication adaptations to accommodate the evolving experiment and scientific requirements are also described in this paper.« less

Evolution of Gas Cell Targets for Magnetized Liner Inertial Fusion Experiments at the Sandia National Laboratories PECOS Test Facility

DOE PAGES

Paguio, R. R.; Smith, G. E.; Taylor, J. L.; ...

2017-12-04

Z-Beamlet (ZBL) experiments conducted at the PECOS test facility at Sandia National Laboratories (SNL) investigated the nonlinear processes in laser plasma interaction (or laserplasma instabilities LPI) that complicate the deposition of laser energy by enhanced absorption, backscatter, filamentation and beam-spray that can occur in large-scale laser-heated gas cell targets. These targets and experiments were designed to provide better insight into the physics of the laser preheat stage of the Magnetized Liner Inertial Fusion (MagLIF) scheme being tested on the SNL Z-machine. The experiments aim to understand the tradeoffs between laser spot size, laser pulse shape, laser entrance hole (LEH) windowmore » thickness, and fuel density for laser preheat. Gas cell target design evolution and fabrication adaptations to accommodate the evolving experiment and scientific requirements are also described in this paper.« less

Fixed-target hadron production experiments

NASA Astrophysics Data System (ADS)

Popov, Boris A.

2015-08-01

Results from fixed-target hadroproduction experiments (HARP, MIPP, NA49 and NA61/SHINE) as well as their implications for cosmic ray and neutrino physics are reviewed. HARP measurements have been used for predictions of neutrino beams in K2K and MiniBooNE/SciBooNE experiments and are also being used to improve predictions of the muon yields in EAS and of the atmospheric neutrino fluxes as well as to help in the optimization of neutrino factory and super-beam designs. Recent measurements released by the NA61/SHINE experiment are of significant importance for a precise prediction of the J-PARC neutrino beam used for the T2K experiment and for interpretation of EAS data. These hadroproduction experiments provide also a large amount of input for validation and tuning of hadron production models in Monte-Carlo generators.

The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

PubMed

Li, Ying Hong; Wang, Pan Pan; Li, Xiao Xu; Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

2016-01-01

The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

Drug-target interaction prediction: A Bayesian ranking approach.

PubMed

Peska, Ladislav; Buza, Krisztian; Koller, Júlia

2017-12-01

In silico prediction of drug-target interactions (DTI) could provide valuable information and speed-up the process of drug repositioning - finding novel usage for existing drugs. In our work, we focus on machine learning algorithms supporting drug-centric repositioning approach, which aims to find novel usage for existing or abandoned drugs. We aim at proposing a per-drug ranking-based method, which reflects the needs of drug-centric repositioning research better than conventional drug-target prediction approaches. We propose Bayesian Ranking Prediction of Drug-Target Interactions (BRDTI). The method is based on Bayesian Personalized Ranking matrix factorization (BPR) which has been shown to be an excellent approach for various preference learning tasks, however, it has not been used for DTI prediction previously. In order to successfully deal with DTI challenges, we extended BPR by proposing: (i) the incorporation of target bias, (ii) a technique to handle new drugs and (iii) content alignment to take structural similarities of drugs and targets into account. Evaluation on five benchmark datasets shows that BRDTI outperforms several state-of-the-art approaches in terms of per-drug nDCG and AUC. BRDTI results w.r.t. nDCG are 0.929, 0.953, 0.948, 0.897 and 0.690 for G-Protein Coupled Receptors (GPCR), Ion Channels (IC), Nuclear Receptors (NR), Enzymes (E) and Kinase (K) datasets respectively. Additionally, BRDTI significantly outperformed other methods (BLM-NII, WNN-GIP, NetLapRLS and CMF) w.r.t. nDCG in 17 out of 20 cases. Furthermore, BRDTI was also shown to be able to predict novel drug-target interactions not contained in the original datasets. The average recall at top-10 predicted targets for each drug was 0.762, 0.560, 1.000 and 0.404 for GPCR, IC, NR, and E datasets respectively. Based on the evaluation, we can conclude that BRDTI is an appropriate choice for researchers looking for an in silico DTI prediction technique to be used in drug

DrugE-Rank: improving drug–target interaction prediction of new candidate drugs or targets by ensemble learning to rank

PubMed Central

Yuan, Qingjun; Gao, Junning; Wu, Dongliang; Zhang, Shihua; Mamitsuka, Hiroshi; Zhu, Shanfeng

2016-01-01

Motivation: Identifying drug–target interactions is an important task in drug discovery. To reduce heavy time and financial cost in experimental way, many computational approaches have been proposed. Although these approaches have used many different principles, their performance is far from satisfactory, especially in predicting drug–target interactions of new candidate drugs or targets. Methods: Approaches based on machine learning for this problem can be divided into two types: feature-based and similarity-based methods. Learning to rank is the most powerful technique in the feature-based methods. Similarity-based methods are well accepted, due to their idea of connecting the chemical and genomic spaces, represented by drug and target similarities, respectively. We propose a new method, DrugE-Rank, to improve the prediction performance by nicely combining the advantages of the two different types of methods. That is, DrugE-Rank uses LTR, for which multiple well-known similarity-based methods can be used as components of ensemble learning. Results: The performance of DrugE-Rank is thoroughly examined by three main experiments using data from DrugBank: (i) cross-validation on FDA (US Food and Drug Administration) approved drugs before March 2014; (ii) independent test on FDA approved drugs after March 2014; and (iii) independent test on FDA experimental drugs. Experimental results show that DrugE-Rank outperforms competing methods significantly, especially achieving more than 30% improvement in Area under Prediction Recall curve for FDA approved new drugs and FDA experimental drugs. Availability: http://datamining-iip.fudan.edu.cn/service/DrugE-Rank Contact: zhusf@fudan.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307615

DrugE-Rank: improving drug-target interaction prediction of new candidate drugs or targets by ensemble learning to rank.

PubMed

Yuan, Qingjun; Gao, Junning; Wu, Dongliang; Zhang, Shihua; Mamitsuka, Hiroshi; Zhu, Shanfeng

2016-06-15

Identifying drug-target interactions is an important task in drug discovery. To reduce heavy time and financial cost in experimental way, many computational approaches have been proposed. Although these approaches have used many different principles, their performance is far from satisfactory, especially in predicting drug-target interactions of new candidate drugs or targets. Approaches based on machine learning for this problem can be divided into two types: feature-based and similarity-based methods. Learning to rank is the most powerful technique in the feature-based methods. Similarity-based methods are well accepted, due to their idea of connecting the chemical and genomic spaces, represented by drug and target similarities, respectively. We propose a new method, DrugE-Rank, to improve the prediction performance by nicely combining the advantages of the two different types of methods. That is, DrugE-Rank uses LTR, for which multiple well-known similarity-based methods can be used as components of ensemble learning. The performance of DrugE-Rank is thoroughly examined by three main experiments using data from DrugBank: (i) cross-validation on FDA (US Food and Drug Administration) approved drugs before March 2014; (ii) independent test on FDA approved drugs after March 2014; and (iii) independent test on FDA experimental drugs. Experimental results show that DrugE-Rank outperforms competing methods significantly, especially achieving more than 30% improvement in Area under Prediction Recall curve for FDA approved new drugs and FDA experimental drugs. http://datamining-iip.fudan.edu.cn/service/DrugE-Rank zhusf@fudan.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Young Children's Prosocial and Aggressive Behaviors and Their Experiences of Being Targeted for Similar Behaviors by Peers

ERIC Educational Resources Information Center

Persson, Gun E. B.

2005-01-01

Children's target experiences (as recipients of prosocial peer acts and victims of peer aggression) were investigated for their concurrent and longitudinal associations with prosocial and aggressive behavior. Forty-four children (initially 22-40 months) were observed in naturalistic interactions with peers during a two-month period for each of…

Tertiary structure-based analysis of microRNA–target interactions

PubMed Central

Gan, Hin Hark; Gunsalus, Kristin C.

2013-01-01

Current computational analysis of microRNA interactions is based largely on primary and secondary structure analysis. Computationally efficient tertiary structure-based methods are needed to enable more realistic modeling of the molecular interactions underlying miRNA-mediated translational repression. We incorporate algorithms for predicting duplex RNA structures, ionic strength effects, duplex entropy and free energy, and docking of duplex–Argonaute protein complexes into a pipeline to model and predict miRNA–target duplex binding energies. To ensure modeling accuracy and computational efficiency, we use an all-atom description of RNA and a continuum description of ionic interactions using the Poisson–Boltzmann equation. Our method predicts the conformations of two constructs of Caenorhabditis elegans let-7 miRNA–target duplexes to an accuracy of ∼3.8 Å root mean square distance of their NMR structures. We also show that the computed duplex formation enthalpies, entropies, and free energies for eight miRNA–target duplexes agree with titration calorimetry data. Analysis of duplex–Argonaute docking shows that structural distortions arising from single-base-pair mismatches in the seed region influence the activity of the complex by destabilizing both duplex hybridization and its association with Argonaute. Collectively, these results demonstrate that tertiary structure-based modeling of miRNA interactions can reveal structural mechanisms not accessible with current secondary structure-based methods. PMID:23417009

Chemical modification of projectile residues and target material in a MEMIN cratering experiment

NASA Astrophysics Data System (ADS)

Ebert, Matthias; Hecht, Lutz; Deutsch, Alexander; Kenkmann, Thomas

2013-01-01

In the context of the MEMIN project, a hypervelocity cratering experiment has been performed using a sphere of the iron meteorite Campo del Cielo as projectile accelerated to 4.56 km s-1, and a block of Seeberger sandstone as target material. The ejecta, collected in a newly designed catcher, are represented by (1) weakly deformed, (2) highly deformed, and (3) highly shocked material. The latter shows shock-metamorphic features such as planar deformation features (PDF) in quartz, formation of diaplectic quartz glass, partial melting of the sandstone, and partially molten projectile, mixed mechanically and chemically with target melt. During mixing of projectile and target melts, the Fe of the projectile is preferentially partitioned into target melt to a greater degree than Ni and Co yielding a Fe/Ni that is generally higher than Fe/Ni in the projectile. This fractionation results from the differing siderophile properties, specifically from differences in reactivity of Fe, Ni, and Co with oxygen during projectile-target interaction. Projectile matter was also detected in shocked quartz grains. The average Fe/Ni of quartz with PDF (about 20) and of silica glasses (about 24) are in contrast to the average sandstone ratio (about 422), but resembles the Fe/Ni-ratio of the projectile (about 14). We briefly discuss possible reasons of projectile melting and vaporization in the experiment, in which the calculated maximum shock pressure does not exceed 55 GPa.

Inferring protein domains associated with drug side effects based on drug-target interaction network.

PubMed

Iwata, Hiroaki; Mizutani, Sayaka; Tabei, Yasuo; Kotera, Masaaki; Goto, Susumu; Yamanishi, Yoshihiro

2013-01-01

Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.

The effects of return current and target charging in short pulse high intensity laser interactions

NASA Astrophysics Data System (ADS)

Beg, Farhat

2003-10-01

Since the introduction of the technique of chirped pulse amplification (CPA), peak laser intensities have increased dramatically. It is now possible to perform laser-plasma interaction experiments at intensities approaching 1021 Wcm-2. The electrons in the field of such lasers are highly relativistic (gamma 31) and the temperature of the hot electron distribution produced in a plasma at such extreme intensities can exceed 10 MeV. Since the resulting beam current exceeds the Alfvén limit, a neutralizing return current of cold plasma electrons moving in the opposite direction is produced. Another source of return current is that due to the escape of very energetic electrons from the target, which then creates a large electrostatic potential due to charge separation. These return currents can cause significant ohmic heating. We present results from experiments performed at Rutherford Appleton Laboratory using the VULCAN laser facility (I> 5 x1019 Wcm-2). Single wire targets were used and in some shots a secondary wire or foil was placed near the target. Three main observations were made: (i) generation of a Z-pinch in the wire due to the return current, (ii) optical transition radiation at 2w and (iii) proton emission from both the primary wire target and the secondary wire or foil. The Z-pinch was observed to be m=0 unstable. The current was estimated to be about 0.8 MA using simple energy balance considerations. Intense second harmonic emission due to coherent optical transition radiation from both the primary target and secondary objects was observed and is likely due to electron bunches accelerated by the ponderomotive jxB force of the laser. The proton emission from the secondary wire or foil was likely due to field emission of electrons from the these objects in response to the large potential produced from charging of the primary target. Results of simulations to model these interactions will also be presented.

First PIC simulations modeling the interaction of ultra-intense lasers with sub-micron, liquid crystal targets

NASA Astrophysics Data System (ADS)

McMahon, Matthew; Poole, Patrick; Willis, Christopher; Andereck, David; Schumacher, Douglass

2014-10-01

We recently introduced liquid crystal films as on-demand, variable thickness (50-5000 nanometers), low cost targets for intense laser experiments. Here we present the first particle-in-cell (PIC) simulations of short pulse laser excitation of liquid crystal targets treating Scarlet (OSU) class lasers using the PIC code LSP. In order to accurately model the target evolution, a low starting temperature and field ionization model are employed. This is essential as large starting temperatures, often used to achieve large Debye lengths, lead to expansion of the target causing significant reduction of the target density before the laser pulse can interact. We also present an investigation of the modification of laser pulses by very thin targets. This work was supported by the DARPA PULSE program through a grant from ARMDEC, by the US Department of Energy under Contract No. DE-NA0001976, and allocations of computing time from the Ohio Supercomputing Center.

Human Cancer and Platelet Interaction, a Potential Therapeutic Target.

PubMed

Wang, Shike; Li, Zhenyu; Xu, Ren

2018-04-20

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce cancer-related thrombosis. Here, we discuss the potential function of platelets in regulating cancer progression and summarize the factors and signaling pathways that mediate the cancer cell-platelet interaction.

Inferring protein domains associated with drug side effects based on drug-target interaction network

PubMed Central

2013-01-01

Background Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. Results In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. Conclusion The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains. PMID:24565527

Predicting Drug-Target Interactions Based on Small Positive Samples.

PubMed

Hu, Pengwei; Chan, Keith C C; Hu, Yanxing

2018-01-01

A basic task in drug discovery is to find new medication in the form of candidate compounds that act on a target protein. In other words, a drug has to interact with a target and such drug-target interaction (DTI) is not expected to be random. Significant and interesting patterns are expected to be hidden in them. If these patterns can be discovered, new drugs are expected to be more easily discoverable. Currently, a number of computational methods have been proposed to predict DTIs based on their similarity. However, such as approach does not allow biochemical features to be directly considered. As a result, some methods have been proposed to try to discover patterns in physicochemical interactions. Since the number of potential negative DTIs are very high both in absolute terms and in comparison to that of the known ones, these methods are rather computationally expensive and they can only rely on subsets, rather than the full set, of negative DTIs for training and validation. As there is always a relatively high chance for negative DTIs to be falsely identified and as only partial subset of such DTIs is considered, existing approaches can be further improved to better predict DTIs. In this paper, we present a novel approach, called ODT (one class drug target interaction prediction), for such purpose. One main task of ODT is to discover association patterns between interacting drugs and proteins from the chemical structure of the former and the protein sequence network of the latter. ODT does so in two phases. First, the DTI-network is transformed to a representation by structural properties. Second, it applies a oneclass classification algorithm to build a prediction model based only on known positive interactions. We compared the best AUROC scores of the ODT with several state-of-art approaches on Gold standard data. The prediction accuracy of the ODT is superior in comparison with all the other methods at GPCRs dataset and Ion channels dataset. Performance

Experiences with Interactive Multi-touch Tables

NASA Astrophysics Data System (ADS)

Fikkert, Wim; Hakvoort, Michiel; van der Vet, Paul; Nijholt, Anton

Interactive multi-touch tables can be a powerful means of communication for collaborative work as well as an engaging environment for competition. Through enticing gameplay we have evaluated user experience on competitive gameplay, collaborative work and musical expression. In addition, we report on our extensive experiences with two types of interactive multi-touch tables and we introduce a software framework that abstracts from their technical differences.

Protein-protein interactions and cancer: targeting the central dogma.

PubMed

Garner, Amanda L; Janda, Kim D

2011-01-01

Between 40,000 and 200,000 protein-protein interactions have been predicted to exist within the human interactome. As these interactions are of a critical nature in many important cellular functions and their dysregulation is causal of disease, the modulation of these binding events has emerged as a leading, yet difficult therapeutic arena. In particular, the targeting of protein-protein interactions relevant to cancer is of fundamental importance as the tumor-promoting function of several aberrantly expressed proteins in the cancerous state is directly resultant of its ability to interact with a protein-binding partner. Of significance, these protein complexes play a crucial role in each of the steps of the central dogma of molecular biology, the fundamental processes of genetic transmission. With the many important discoveries being made regarding the mechanisms of these genetic process, the identification of new chemical probes are needed to better understand and validate the druggability of protein-protein interactions related to the central dogma. In this review, we provide an overview of current small molecule-based protein-protein interaction inhibitors for each stage of the central dogma: transcription, mRNA splicing and translation. Importantly, through our analysis we have uncovered a lack of necessary probes targeting mRNA splicing and translation, thus, opening up the possibility for expansion of these fields.

Front surface structured targets for enhancing laser-plasma interactions

NASA Astrophysics Data System (ADS)

Snyder, Joseph; George, Kevin; Ji, Liangliang; Yalamanchili, Sasir; Simonoff, Ethan; Cochran, Ginevra; Daskalova, Rebecca; Poole, Patrick; Willis, Christopher; Lewis, Nathan; Schumacher, Douglass

2016-10-01

We present recent progress made using front surface structured interfaces for enhancing ultrashort, relativistic laser-plasma interactions. Structured targets can increase laser absorption and enhance ion acceleration through a number of mechanisms such as direct laser acceleration and laser guiding. We detail experimental results obtained at the Scarlet laser facility on hollow, micron-scale plasma channels for enhancing electron acceleration. These targets show a greater than three times enhancement in the electron cutoff energy as well as an increased slope temperature for the electron distribution when compared to a flat interface. Using three-dimensional particle-in-cell (PIC) simulations, we have modeled the interaction to give insight into the physical processes responsible for the enhancement. Furthermore, we have used PIC simulations to design structures that are more advantageous for ion acceleration. Such targets necessitate advanced target fabrication methods and we describe techniques used to manufacture optimized structures, including vapor-liquid-solid growth, cryogenic etching, and 3D printing using two-photon-polymerization. This material is based upon work supported by the Air Force Office of Scientific Research under Award Number FA9550-14-1-0085.

Targeting RNA–Protein Interactions within the Human Immunodeficiency Virus Type 1 Lifecycle

PubMed Central

2013-01-01

RNA–protein interactions are vital throughout the HIV-1 life cycle for the successful production of infectious virus particles. One such essential RNA–protein interaction occurs between the full-length genomic viral RNA and the major structural protein of the virus. The initial interaction is between the Gag polyprotein and the viral RNA packaging signal (psi or Ψ), a highly conserved RNA structural element within the 5′-UTR of the HIV-1 genome, which has gained attention as a potential therapeutic target. Here, we report the application of a target-based assay to identify small molecules, which modulate the interaction between Gag and Ψ. We then demonstrate that one such molecule exhibits potent inhibitory activity in a viral replication assay. The mode of binding of the lead molecules to the RNA target was characterized by 1H NMR spectroscopy. PMID:24358934

Drug Target Protein-Protein Interaction Networks: A Systematic Perspective

PubMed Central

2017-01-01

The identification and validation of drug targets are crucial in biomedical research and many studies have been conducted on analyzing drug target features for getting a better understanding on principles of their mechanisms. But most of them are based on either strong biological hypotheses or the chemical and physical properties of those targets separately. In this paper, we investigated three main ways to understand the functional biomolecules based on the topological features of drug targets. There are no significant differences between targets and common proteins in the protein-protein interactions network, indicating the drug targets are neither hub proteins which are dominant nor the bridge proteins. According to some special topological structures of the drug targets, there are significant differences between known targets and other proteins. Furthermore, the drug targets mainly belong to three typical communities based on their modularity. These topological features are helpful to understand how the drug targets work in the PPI network. Particularly, it is an alternative way to predict potential targets or extract nontargets to test a new drug target efficiently and economically. By this way, a drug target's homologue set containing 102 potential target proteins is predicted in the paper. PMID:28691014

New Equilibrium Models of Drug-Receptor Interactions Derived from Target-Mediated Drug Disposition.

PubMed

Peletier, Lambertus A; Gabrielsson, Johan

2018-05-14

In vivo analyses of pharmacological data are traditionally based on a closed system approach not incorporating turnover of target and ligand-target kinetics, but mainly focussing on ligand-target binding properties. This study incorporates information about target and ligand-target kinetics parallel to binding. In a previous paper, steady-state relationships between target- and ligand-target complex versus ligand exposure were derived and a new expression of in vivo potency was derived for a circulating target. This communication is extending the equilibrium relationships and in vivo potency expression for (i) two separate targets competing for one ligand, (ii) two different ligands competing for a single target and (iii) a single ligand-target interaction located in tissue. The derived expressions of the in vivo potencies will be useful both in drug-related discovery projects and mechanistic studies. The equilibrium states of two targets and one ligand may have implications in safety assessment, whilst the equilibrium states of two competing ligands for one target may cast light on when pharmacodynamic drug-drug interactions are important. The proposed equilibrium expressions for a peripherally located target may also be useful for small molecule interactions with extravascularly located targets. Including target turnover, ligand-target complex kinetics and binding properties in expressions of potency and efficacy will improve our understanding of within and between-individual (and across species) variability. The new expressions of potencies highlight the fact that the level of drug-induced target suppression is very much governed by target turnover properties rather than by the target expression level as such.

Cosmic-ray interaction data for designing biological experiments in space.

PubMed

Straume, T; Slaba, T C; Bhattacharya, S; Braby, L A

2017-05-01

There is growing interest in flying biological experiments beyond low-Earth orbit (LEO) to measure biological responses potentially relevant to those expected during a human mission to Mars. Such experiments could be payloads onboard precursor missions, including unmanned private-public partnerships, as well as small low-cost spacecraft (satellites) designed specifically for biosentinel-type missions. It is the purpose of this paper to provide physical cosmic-ray interaction data and related information useful to biologists who may be planning such experiments. It is not the objective here to actually design such experiments or provide radiobiological response functions, which would be specific for each experiment and biological endpoint. Nuclide-specific flux and dose rates were calculated using OLTARIS and these results were used to determine particle traversal rates and doses in hypothetical biological targets. Comparisons are provided between GCR in interplanetary space and inside the ISS. Calculated probabilistic estimates of dose from solar particle events are also presented. Although the focus here is on biological experiments, the information provided may be useful for designing other payloads as well if the space radiation environment is a factor to be considered. Published by Elsevier Ltd.

Cosmic-ray interaction data for designing biological experiments in space

NASA Astrophysics Data System (ADS)

Straume, T.; Slaba, T. C.; Bhattacharya, S.; Braby, L. A.

2017-05-01

There is growing interest in flying biological experiments beyond low-Earth orbit (LEO) to measure biological responses potentially relevant to those expected during a human mission to Mars. Such experiments could be payloads onboard precursor missions, including unmanned private-public partnerships, as well as small low-cost spacecraft (satellites) designed specifically for biosentinel-type missions. It is the purpose of this paper to provide physical cosmic-ray interaction data and related information useful to biologists who may be planning such experiments. It is not the objective here to actually design such experiments or provide radiobiological response functions, which would be specific for each experiment and biological endpoint. Nuclide-specific flux and dose rates were calculated using OLTARIS and these results were used to determine particle traversal rates and doses in hypothetical biological targets. Comparisons are provided between GCR in interplanetary space and inside the ISS. Calculated probabilistic estimates of dose from solar particle events are also presented. Although the focus here is on biological experiments, the information provided may be useful for designing other payloads as well if the space radiation environment is a factor to be considered.

Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

PubMed

Gibiansky, Leonid; Gibiansky, Ekaterina

2018-02-01

The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

Target selection biases from recent experience transfer across effectors.

PubMed

Moher, Jeff; Song, Joo-Hyun

2016-02-01

Target selection is often biased by an observer's recent experiences. However, not much is known about whether these selection biases influence behavior across different effectors. For example, does looking at a red object make it easier to subsequently reach towards another red object? In the current study, we asked observers to find the uniquely colored target object on each trial. Randomly intermixed pre-trial cues indicated the mode of action: either an eye movement or a visually guided reach movement to the target. In Experiment 1, we found that priming of popout, reflected in faster responses following repetition of the target color on consecutive trials, occurred regardless of whether the effector was repeated from the previous trial or not. In Experiment 2, we examined whether an inhibitory selection bias away from a feature could transfer across effectors. While priming of popout reflects both enhancement of the repeated target features and suppression of the repeated distractor features, the distractor previewing effect isolates a purely inhibitory component of target selection in which a previewed color is presented in a homogenous display and subsequently inhibited. Much like priming of popout, intertrial suppression biases in the distractor previewing effect transferred across effectors. Together, these results suggest that biases for target selection driven by recent trial history transfer across effectors. This indicates that representations in memory that bias attention towards or away from specific features are largely independent from their associated actions.

NDCX-II target experiments and simulations

DOE PAGES

Barnard, J. J.; More, R. M.; Terry, M.; ...

2013-06-13

The ion accelerator NDCX-II is undergoing commissioning at Lawrence Berkeley National Laboratory (LBNL). Its principal mission is to explore ion-driven High Energy Density Physics (HEDP) relevant to Inertial Fusion Energy (IFE) especially in the Warm Dense Matter (WDM) regime. We have carried out hydrodynamic simulations of beam-heated targets for parameters expected for the initial configuration of NDCX-II. For metal foils of order one micron thick (thin targets), the beam is predicted to heat the target in a timescale comparable to the hydrodynamic expansion time for experiments that infer material properties from measurements of the resulting rarefaction wave. We have alsomore » carried out hydrodynamic simulations of beam heating of metallic foam targets several tens of microns thick (thick targets) in which the ion range is shorter than the areal density of the material. In this case shock waves will form and we derive simple scaling laws for the efficiency of conversion of ion energy into kinetic energy of fluid flow. Geometries with a tamping layer may also be used to study the merging of a tamper shock with the end-of-range shock. As a result, this process can occur in tamped, direct drive IFE targets.« less

Laser-Plasma Interaction Experiments at Direct-Drive Ignition-Relevant Plasma Conditions at the National Ignition Facility

NASA Astrophysics Data System (ADS)

Solodov, A. A.; Rosenberg, M. J.; Myatt, J. F.; Shaw, J. G.; Seka, W.; Epstein, R.; Short, R. W.; Follett, R. K.; Regan, S. P.; Froula, D. H.; Radha, P. B.; Michel, P.; Chapman, T.; Hohenberger, M.

2017-10-01

Laser-plasma interaction (LPI) instabilities, such as stimulated Raman scattering (SRS) and two-plasmon decay, can be detrimental for direct-drive inertial confinement fusion because of target preheat by the high-energy electrons they generate. The radiation-hydrodynamic code DRACO was used to design planar-target experiments at the National Ignition Facility that generated plasma and interaction conditions relevant to ignition direct-drive designs (IL 1015W/cm2 , Te > 3 keV, density gradient scale lengths of Ln 600 μm). Laser-energy conversion efficiency to hot electrons of 0.5% to 2.5% with temperature of 45 to 60 keV was inferred from the experiment when the laser intensity at the quarter-critical surface increased from 6 to 15 ×1014W/cm2 . LPI was dominated by SRS, as indicated by the measured scattered-light spectra. Simulations of SRS using the LPI code LPSE have been performed and compared with predictions of theoretical models. Implications for ignition-scale direct-drive experiments will be discussed. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

Affective loop experiences: designing for interactional embodiment.

PubMed

Höök, Kristina

2009-12-12

Involving our corporeal bodies in interaction can create strong affective experiences. Systems that both can be influenced by and influence users corporeally exhibit a use quality we name an affective loop experience. In an affective loop experience, (i) emotions are seen as processes, constructed in the interaction, starting from everyday bodily, cognitive or social experiences; (ii) the system responds in ways that pull the user into the interaction, touching upon end users' physical experiences; and (iii) throughout the interaction the user is an active, meaning-making individual choosing how to express themselves-the interpretation responsibility does not lie with the system. We have built several systems that attempt to create affective loop experiences with more or less successful results. For example, eMoto lets users send text messages between mobile phones, but in addition to text, the messages also have colourful and animated shapes in the background chosen through emotion-gestures with a sensor-enabled stylus pen. Affective Diary is a digital diary with which users can scribble their notes, but it also allows for bodily memorabilia to be recorded from body sensors mapping to users' movement and arousal and placed along a timeline. Users can see patterns in their bodily reactions and relate them to various events going on in their lives. The experiences of building and deploying these systems gave us insights into design requirements for addressing affective loop experiences, such as how to design for turn-taking between user and system, how to create for 'open' surfaces in the design that can carry users' own meaning-making processes, how to combine modalities to create for a 'unity' of expression, and the importance of mirroring user experience in familiar ways that touch upon their everyday social and corporeal experiences. But a more important lesson gained from deploying the systems is how emotion processes are co-constructed and experienced

Affective loop experiences: designing for interactional embodiment

PubMed Central

Höök, Kristina

2009-01-01

Involving our corporeal bodies in interaction can create strong affective experiences. Systems that both can be influenced by and influence users corporeally exhibit a use quality we name an affective loop experience. In an affective loop experience, (i) emotions are seen as processes, constructed in the interaction, starting from everyday bodily, cognitive or social experiences; (ii) the system responds in ways that pull the user into the interaction, touching upon end users' physical experiences; and (iii) throughout the interaction the user is an active, meaning-making individual choosing how to express themselves—the interpretation responsibility does not lie with the system. We have built several systems that attempt to create affective loop experiences with more or less successful results. For example, eMoto lets users send text messages between mobile phones, but in addition to text, the messages also have colourful and animated shapes in the background chosen through emotion-gestures with a sensor-enabled stylus pen. Affective Diary is a digital diary with which users can scribble their notes, but it also allows for bodily memorabilia to be recorded from body sensors mapping to users' movement and arousal and placed along a timeline. Users can see patterns in their bodily reactions and relate them to various events going on in their lives. The experiences of building and deploying these systems gave us insights into design requirements for addressing affective loop experiences, such as how to design for turn-taking between user and system, how to create for ‘open’ surfaces in the design that can carry users' own meaning-making processes, how to combine modalities to create for a ‘unity’ of expression, and the importance of mirroring user experience in familiar ways that touch upon their everyday social and corporeal experiences. But a more important lesson gained from deploying the systems is how emotion processes are co-constructed and

An Experiment Quantifying The Effect Of Clutter On Target Detection

NASA Astrophysics Data System (ADS)

Weathersby, Marshall R.; Schmieder, David E.

1985-01-01

Experiments were conducted to determine the influence of background clutter on target detection criteria. The experiment consisted of placing observers in front of displayed images on a TV monitor. Observer ability to detect military targets embedded in simulated natural and manmade background clutter was measured when there was unlimited viewing time. Results were described in terms of detection probability versus target resolution for various signal to clutter ratios (SCR). The experiments were preceded by a search for a meaningful clutter definition. The selected definition was a statistical measure computed by averaging the standard deviation of contiguous scene cells over the whole scene. The cell size was comparable to the target size. Observer test results confirmed the expectation that the resolution required for a given detection probability was a continuum function of the clutter level. At the lower SCRs the resolution required for a high probability of detection was near 6 lines pairs per target (LP/TGT), while at the higher SCRs it was found that a resolution of less than 0.25 LP/TGT would yield a high probability of detection. These results are expected to aid in target acquisition performance modeling and to lead to improved specifications for imaging automatic target screeners.

Time Critical Targeting Concept of Operations (CONOPS) Interactions

DTIC Science & Technology

2011-05-01

range of topics in force development and employment. Carl has participated in projects examining the interdiction of armoured ground forces , long...Critical Targeting Concept of Operations (CONOPS) Interactions Executive Summary In 2003, RAND Project Air Force examined the...Attack. ____________________ ________________________________________________ Carl Rhodes Project Air Force , RAND Corporation Carl Rhodes is the

Interactive Screen Experiments with Single Photons

ERIC Educational Resources Information Center

Bronner, Patrick; Strunz, Andreas; Silberhorn, Christine; Meyn, Jan-Peter

2009-01-01

Single photons are used for fundamental quantum physics experiments as well as for applications. Originally being a topic of advance courses, such experiments are increasingly a subject of undergraduate courses. We provide interactive screen experiments (ISE) for supporting the work in a real laboratory, and for students who do not have access to…

The polarised internal target for the PAX experiment

NASA Astrophysics Data System (ADS)

Ciullo, G.; Barion, L.; Barschel, C.; Grigoriev, K.; Lenisa, P.; Nass, A.; Sarkadi, J.; Statera, M.; Steffens, E.; Tagliente, G.

2011-05-01

The PAX (Polarized Antiproton eXperiment) collaboration aims to polarise antiproton beams stored in ring by means of spin-filtering. The experimental setup is based on a polarised internal gas target, surrounded by a detection system for the measurement of spin observables. In this report, we present results from the commission of the PAX target (atomic beam source, openable cell, and polarimeter).

Targeting protein-protein interactions with trimeric ligands: high affinity inhibitors of the MAGUK protein family.

PubMed

Nissen, Klaus B; Haugaard-Kedström, Linda M; Wilbek, Theis S; Nielsen, Line S; Åberg, Emma; Kristensen, Anders S; Bach, Anders; Jemth, Per; Strømgaard, Kristian

2015-01-01

PDZ domains in general, and those of PSD-95 in particular, are emerging as promising drug targets for diseases such as ischemic stroke. We have previously shown that dimeric ligands that simultaneously target PDZ1 and PDZ2 of PSD-95 are highly potent inhibitors of PSD-95. However, PSD-95 and the related MAGUK proteins contain three consecutive PDZ domains, hence we envisioned that targeting all three PDZ domains simultaneously would lead to more potent and potentially more specific interactions with the MAGUK proteins. Here we describe the design, synthesis and characterization of a series of trimeric ligands targeting all three PDZ domains of PSD-95 and the related MAGUK proteins, PSD-93, SAP-97 and SAP-102. Using our dimeric ligands targeting the PDZ1-2 tandem as starting point, we designed novel trimeric ligands by introducing a PDZ3-binding peptide moiety via a cysteine-derivatized NPEG linker. The trimeric ligands generally displayed increased affinities compared to the dimeric ligands in fluorescence polarization binding experiments and optimized trimeric ligands showed low nanomolar inhibition towards the four MAGUK proteins, thus being the most potent inhibitors described. Kinetic experiments using stopped-flow spectrometry showed that the increase in affinity is caused by a decrease in the dissociation rate of the trimeric ligand as compared to the dimeric ligands, likely reflecting the lower probability of simultaneous dissociation of all three PDZ ligands. Thus, we have provided novel inhibitors of the MAGUK proteins with exceptionally high affinity, which can be used to further elucidate the therapeutic potential of these proteins.

AlphaSpace: Fragment-Centric Topographical Mapping To Target Protein–Protein Interaction Interfaces

PubMed Central

2016-01-01

Inhibition of protein–protein interactions (PPIs) is emerging as a promising therapeutic strategy despite the difficulty in targeting such interfaces with drug-like small molecules. PPIs generally feature large and flat binding surfaces as compared to typical drug targets. These features pose a challenge for structural characterization of the surface using geometry-based pocket-detection methods. An attractive mapping strategy—that builds on the principles of fragment-based drug discovery (FBDD)—is to detect the fragment-centric modularity at the protein surface and then characterize the large PPI interface as a set of localized, fragment-targetable interaction regions. Here, we introduce AlphaSpace, a computational analysis tool designed for fragment-centric topographical mapping (FCTM) of PPI interfaces. Our approach uses the alpha sphere construct, a geometric feature of a protein’s Voronoi diagram, to map out concave interaction space at the protein surface. We introduce two new features—alpha-atom and alpha-space—and the concept of the alpha-atom/alpha-space pair to rank pockets for fragment-targetability and to facilitate the evaluation of pocket/fragment complementarity. The resulting high-resolution interfacial map of targetable pocket space can be used to guide the rational design and optimization of small molecule or biomimetic PPI inhibitors. PMID:26225450

Statistical analysis of target acquisition sensor modeling experiments

NASA Astrophysics Data System (ADS)

Deaver, Dawne M.; Moyer, Steve

2015-05-01

The U.S. Army RDECOM CERDEC NVESD Modeling and Simulation Division is charged with the development and advancement of military target acquisition models to estimate expected soldier performance when using all types of imaging sensors. Two elements of sensor modeling are (1) laboratory-based psychophysical experiments used to measure task performance and calibrate the various models and (2) field-based experiments used to verify the model estimates for specific sensors. In both types of experiments, it is common practice to control or measure environmental, sensor, and target physical parameters in order to minimize uncertainty of the physics based modeling. Predicting the minimum number of test subjects required to calibrate or validate the model should be, but is not always, done during test planning. The objective of this analysis is to develop guidelines for test planners which recommend the number and types of test samples required to yield a statistically significant result.

Fuzzy Neural Network-Based Interacting Multiple Model for Multi-Node Target Tracking Algorithm

PubMed Central

Sun, Baoliang; Jiang, Chunlan; Li, Ming

2016-01-01

An interacting multiple model for multi-node target tracking algorithm was proposed based on a fuzzy neural network (FNN) to solve the multi-node target tracking problem of wireless sensor networks (WSNs). Measured error variance was adaptively adjusted during the multiple model interacting output stage using the difference between the theoretical and estimated values of the measured error covariance matrix. The FNN fusion system was established during multi-node fusion to integrate with the target state estimated data from different nodes and consequently obtain network target state estimation. The feasibility of the algorithm was verified based on a network of nine detection nodes. Experimental results indicated that the proposed algorithm could trace the maneuvering target effectively under sensor failure and unknown system measurement errors. The proposed algorithm exhibited great practicability in the multi-node target tracking of WSNs. PMID:27809271

Druggable orthosteric and allosteric hot spots to target protein-protein interactions.

PubMed

Ma, Buyong; Nussinov, Ruth

2014-01-01

Drug designing targeting protein-protein interactions is challenging. Because structural elucidation and computational analysis have revealed the importance of hot spot residues in stabilizing these interactions, there have been on-going efforts to develop drugs which bind the hot spots and out-compete the native protein partners. The question arises as to what are the key 'druggable' properties of hot spots in protein-protein interactions and whether these mimic the general hot spot definition. Identification of orthosteric (at the protein- protein interaction site) and allosteric (elsewhere) druggable hot spots is expected to help in discovering compounds that can more effectively modulate protein-protein interactions. For example, are there any other significant features beyond their location in pockets in the interface? The interactions of protein-protein hot spots are coupled with conformational dynamics of protein complexes. Currently increasing efforts focus on the allosteric drug discovery. Allosteric drugs bind away from the native binding site and can modulate the native interactions. We propose that identification of allosteric hot spots could similarly help in more effective allosteric drug discovery. While detection of allosteric hot spots is challenging, targeting drugs to these residues has the potential of greatly increasing the hot spot and protein druggability.

Interactive object recognition assistance: an approach to recognition starting from target objects

NASA Astrophysics Data System (ADS)

Geisler, Juergen; Littfass, Michael

1999-07-01

Recognition of target objects in remotely sensed imagery required detailed knowledge about the target object domain as well as about mapping properties of the sensing system. The art of object recognition is to combine both worlds appropriately and to provide models of target appearance with respect to sensor characteristics. Common approaches to support interactive object recognition are either driven from the sensor point of view and address the problem of displaying images in a manner adequate to the sensing system. Or they focus on target objects and provide exhaustive encyclopedic information about this domain. Our paper discusses an approach to assist interactive object recognition based on knowledge about target objects and taking into account the significance of object features with respect to characteristics of the sensed imagery, e.g. spatial and spectral resolution. An `interactive recognition assistant' takes the image analyst through the interpretation process by indicating step-by-step the respectively most significant features of objects in an actual set of candidates. The significance of object features is expressed by pregenerated trees of significance, and by the dynamic computation of decision relevance for every feature at each step of the recognition process. In the context of this approach we discuss the question of modeling and storing the multisensorial/multispectral appearances of target objects and object classes as well as the problem of an adequate dynamic human-machine-interface that takes into account various mental models of human image interpretation.

Network Understanding of Herb Medicine via Rapid Identification of Ingredient-Target Interactions

NASA Astrophysics Data System (ADS)

Zhang, Hai-Ping; Pan, Jian-Bo; Zhang, Chi; Ji, Nan; Wang, Hao; Ji, Zhi-Liang

2014-01-01

Today, herb medicines have become the major source for discovery of novel agents in countermining diseases. However, many of them are largely under-explored in pharmacology due to the limitation of current experimental approaches. Therefore, we proposed a computational framework in this study for network understanding of herb pharmacology via rapid identification of putative ingredient-target interactions in human structural proteome level. A marketing anti-cancer herb medicine in China, Yadanzi (Brucea javanica), was chosen for mechanistic study. Total 7,119 ingredient-target interactions were identified for thirteen Yadanzi active ingredients. Among them, about 29.5% were estimated to have better binding affinity than their corresponding marketing drug-target interactions. Further Bioinformatics analyses suggest that simultaneous manipulation of multiple proteins in the MAPK signaling pathway and the phosphorylation process of anti-apoptosis may largely answer for Yadanzi against non-small cell lung cancers. In summary, our strategy provides an efficient however economic solution for systematic understanding of herbs' power.

Network understanding of herb medicine via rapid identification of ingredient-target interactions.

PubMed

Zhang, Hai-Ping; Pan, Jian-Bo; Zhang, Chi; Ji, Nan; Wang, Hao; Ji, Zhi-Liang

2014-01-16

Today, herb medicines have become the major source for discovery of novel agents in countermining diseases. However, many of them are largely under-explored in pharmacology due to the limitation of current experimental approaches. Therefore, we proposed a computational framework in this study for network understanding of herb pharmacology via rapid identification of putative ingredient-target interactions in human structural proteome level. A marketing anti-cancer herb medicine in China, Yadanzi (Brucea javanica), was chosen for mechanistic study. Total 7,119 ingredient-target interactions were identified for thirteen Yadanzi active ingredients. Among them, about 29.5% were estimated to have better binding affinity than their corresponding marketing drug-target interactions. Further Bioinformatics analyses suggest that simultaneous manipulation of multiple proteins in the MAPK signaling pathway and the phosphorylation process of anti-apoptosis may largely answer for Yadanzi against non-small cell lung cancers. In summary, our strategy provides an efficient however economic solution for systematic understanding of herbs' power.

Nanoparticle-macrophage interactions: A balance between clearance and cell-specific targeting

PubMed Central

Rattan, Rahul; Bhattacharjee, Somnath; Zong, Hong; Swain, Corban; Siddiqui, Muneeb A.; Visovatti, Scott H.; Kanthi, Yogendra; Desai, Sajani; Pinsky, David J.; Goonewardena, Sascha N.

2017-01-01

The surface properties of nanoparticles (NPs) are a major factor that influences how these nanomaterials interact with biological systems. Interactions between NPs and macrophages of the reticuloendothelial system (RES) can reduce the efficacy of NP diagnostics and therapeutics. Traditionally, to limit NP clearance by the RES system, the NP surface is neutralized with molecules like poly(ethylene glycol) (PEG) which are known to resist protein adsorption and RES clearance. Unfortunately, PEG modification is not without drawbacks including difficulties with the synthesis and associations with immune reactions. To overcome some of these obstacles, we neutralized the NP surface by acetylation and compared this modification to PEGylation for RES clearance and tumor-specific targeting. We found that acetylation was comparable to PEGylation in reducing RES clearance. Additionally, we found that dendrimer acetylation did not impact folic acid (FA)-mediated targeting of tumor cells whereas PEG surface modification reduced the targeting ability of the NP. These results clarify the impact of different NP surface modifications on RES clearance and cell-specific targeting and provide insights into the design of more effective NPs. PMID:28705434

An in-vacuo optical levitation trap for high-intensity laser interaction experiments with isolated microtargets

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

Price, C. J., E-mail: c.price10@imperial.ac.uk; Giltrap, S.; Stuart, N. H.

2015-03-15

We report on the design, construction, and characterisation of a new class of in-vacuo optical levitation trap optimised for use in high-intensity, high-energy laser interaction experiments. The system uses a focused, vertically propagating continuous wave laser beam to capture and manipulate micro-targets by photon momentum transfer at much longer working distances than commonly used by optical tweezer systems. A high speed (10 kHz) optical imaging and signal acquisition system was implemented for tracking the levitated droplets position and dynamic behaviour under atmospheric and vacuum conditions, with ±5 μm spatial resolution. Optical trapping of 10 ± 4 μm oil droplets inmore » vacuum was demonstrated, over timescales of >1 h at extended distances of ∼40 mm from the final focusing optic. The stability of the levitated droplet was such that it would stay in alignment with a ∼7 μm irradiating beam focal spot for up to 5 min without the need for re-adjustment. The performance of the trap was assessed in a series of high-intensity (10{sup 17} W cm{sup −2}) laser experiments that measured the X-ray source size and inferred free-electron temperature of a single isolated droplet target, along with a measurement of the emitted radio-frequency pulse. These initial tests demonstrated the use of optically levitated microdroplets as a robust target platform for further high-intensity laser interaction and point source studies.« less

An in-vacuo optical levitation trap for high-intensity laser interaction experiments with isolated microtargets

NASA Astrophysics Data System (ADS)

Price, C. J.; Donnelly, T. D.; Giltrap, S.; Stuart, N. H.; Parker, S.; Patankar, S.; Lowe, H. F.; Drew, D.; Gumbrell, E. T.; Smith, R. A.

2015-03-01

We report on the design, construction, and characterisation of a new class of in-vacuo optical levitation trap optimised for use in high-intensity, high-energy laser interaction experiments. The system uses a focused, vertically propagating continuous wave laser beam to capture and manipulate micro-targets by photon momentum transfer at much longer working distances than commonly used by optical tweezer systems. A high speed (10 kHz) optical imaging and signal acquisition system was implemented for tracking the levitated droplets position and dynamic behaviour under atmospheric and vacuum conditions, with ±5 μm spatial resolution. Optical trapping of 10 ± 4 μm oil droplets in vacuum was demonstrated, over timescales of >1 h at extended distances of ˜40 mm from the final focusing optic. The stability of the levitated droplet was such that it would stay in alignment with a ˜7 μm irradiating beam focal spot for up to 5 min without the need for re-adjustment. The performance of the trap was assessed in a series of high-intensity (1017 W cm-2) laser experiments that measured the X-ray source size and inferred free-electron temperature of a single isolated droplet target, along with a measurement of the emitted radio-frequency pulse. These initial tests demonstrated the use of optically levitated microdroplets as a robust target platform for further high-intensity laser interaction and point source studies.

Characterizing the interaction among bullet, body armor, and human and surrogate targets.

PubMed

Shen, Weixin; Niu, Yuqing; Bykanova, Lucy; Laurence, Peter; Link, Norman

2010-12-01

This study used a combined experimental and modeling approach to characterize and quantify the interaction among bullet, body armor, and human surrogate targets during the 10-1000 μs range that is crucial to evaluating the protective effectiveness of body armor against blunt injuries. Ballistic tests incorporating high-speed flash X-ray measurements were performed to acquire the deformations of bullets and body armor samples placed against ballistic clay and gelatin targets with images taken between 10 μs and 1 ms of the initial impact. Finite element models (FEMs) of bullet, armor, and gelatin and clay targets were developed with material parameters selected to best fit model calculations to the test measurements. FEMs of bullet and armor interactions were then assembled with a FEM of a human torso and FEMs of clay and gelatin blocks in the shape of a human torso to examine the effects of target material and geometry on the interaction. Test and simulation results revealed three distinct loading phases during the interaction. In the first phase, the bullet was significantly slowed in about 60 μs as it transferred a major portion of its energy into the body armor. In the second phase, fibers inside the armor were pulled toward the point of impact and kept on absorbing energy until about 100 μs after the initial impact when energy absorption reached its peak. In the third phase, the deformation on the armor's back face continued to grow and energies inside both armor and targets redistributed through wave propagation. The results indicated that armor deformation and energy absorption in the second and third phases were significantly affected by the material properties (density and stiffness) and geometrical characteristics (curvature and gap at the armor-target interface) of the targets. Valid surrogate targets for testing the ballistic resistance of the armor need to account for these factors and produce the same armor deformation and energy absorption as on a

A user-targeted synthesis of the VALUE perfect predictor experiment

NASA Astrophysics Data System (ADS)

Maraun, Douglas; Widmann, Martin; Gutierrez, Jose; Kotlarski, Sven; Hertig, Elke; Wibig, Joanna; Rössler, Ole; Huth, Radan

2016-04-01

VALUE is an open European network to validate and compare downscaling methods for climate change research. A key deliverable of VALUE is the development of a systematic validation framework to enable the assessment and comparison of both dynamical and statistical downscaling methods. VALUE's main approach to validation is user-focused: starting from a specific user problem, a validation tree guides the selection of relevant validation indices and performance measures. We consider different aspects: (1) marginal aspects such as mean, variance and extremes; (2) temporal aspects such as spell length characteristics; (3) spatial aspects such as the de-correlation length of precipitation extremes; and multi-variate aspects such as the interplay of temperature and precipitation or scale-interactions. Several experiments have been designed to isolate specific points in the downscaling procedure where problems may occur. Experiment 1 (perfect predictors): what is the isolated downscaling skill? How do statistical and dynamical methods compare? How do methods perform at different spatial scales? Experiment 2 (Global climate model predictors): how is the overall representation of regional climate, including errors inherited from global climate models? Experiment 3 (pseudo reality): do methods fail in representing regional climate change? Here, we present a user-targeted synthesis of the results of the first VALUE experiment. In this experiment, downscaling methods are driven with ERA-Interim reanalysis data to eliminate global climate model errors, over the period 1979-2008. As reference data we use, depending on the question addressed, (1) observations from 86 meteorological stations distributed across Europe; (2) gridded observations at the corresponding 86 locations or (3) gridded spatially extended observations for selected European regions. With more than 40 contributing methods, this study is the most comprehensive downscaling inter-comparison project so far. The

NIF Target Designs and OMEGA Experiments for Shock-Ignition Inertial Confinement Fusion

NASA Astrophysics Data System (ADS)

Anderson, K. S.

2012-10-01

Shock ignition (SI)footnotetextR. Betti et al., Phys. Rev. Lett. 98, 155001 (2007). is being pursued as a viable option to achieve ignition on the National Ignition Facility (NIF). Shock-ignition target designs require the addition of a high-intensity (˜5 x 10^15 W/cm^2) laser spike at the end of a low-adiabat assembly pulse to launch a spherically convergent strong shock to ignite the imploding capsule. Achieving ignition with SI requires the laser spike to generate an ignitor shock with a launching pressure typically in excess of ˜300 Mbar. At the high laser intensities required during the spike pulse, stimulated Raman (SRS) and Brillouin scattering (SBS) could reflect a significant fraction of the incident light. In addition, SRS and the two-plasmon-decay instability can accelerate hot electrons into the shell and preheat the fuel. Since the high-power spike occurs at the end of the pulse when the areal density of the shell is several tens of mg/cm^2, shock-ignition fuel layers are shielded against hot electrons with energies below 150 keV. This paper will present data for a set of OMEGA experiments that were designed to study laser--plasma interactions during the spike pulse. In addition, these experiments were used to demonstrate that high-pressure shocks can be produced in long-scale-length plasmas with SI-relevant intensities. Within the constraints imposed by the hydrodynamics of strong shock generation and the laser--plasma instabilities, target designs for SI experiments on the NIF will be presented. Two-dimensional radiation--hydrodynamic simulations of SI target designs for the NIF predict ignition in the polar-drive beam configuration at sub-MJ laser energies. Design robustness to various 1-D effects and 2-D nonuniformities has been characterized. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-08NA28302.

Regulation of Blood Pressure by Targeting CaV1.2-Galectin-1 Protein Interaction.

PubMed

Hu, Zhenyu; Li, Guang; Wang, Jiong-Wei; Chong, Suet Yen; Yu, Dejie; Wang, Xiaoyuan; Soon, Jia Lin; Liang, Mui Cheng; Wong, Yuk Peng; Huang, Na; Colecraft, Henry M; Liao, Ping; Soong, Tuck Wah

2018-04-12

Background -L-type Ca V 1.2 channels play crucial roles in regulation of blood pressure. Galectin-1 (Gal-1), has been reported to bind to the I-II loop of Ca V 1.2 channels to reduce their current density. However, the mechanistic understanding for the down-regulation of Ca V 1.2 channels by Gal-1, and whether Gal-1 plays a direct role in blood pressure regulation remain unclear. Methods - In vitro experiments involving co-IP, western blot, patch-clamp recordings, immunohistochemistry and pressure myography were used to evaluate the molecular mechanisms by which Gal-1 down-regulates Ca V 1.2 channel in transfected HEK 293 cells, smooth muscle cells, arteries from Lgasl1 -/- mice, rat and human patients. In vivo experiments involving delivery of Tat-e9c peptide and AAV5-Gal-1 into rats were performed to investigate the effect of targeting Ca V 1.2-Gal-1 interaction on blood pressure monitored by tail cuff or telemetry methods. Results -Our study reveals that Gal-1 is a key regulator for proteasomal degradation of Ca V 1.2 channels. Gal-1 competed allosterically with Ca V β subunit for binding to the I-II loop of Ca V 1.2 channel. This competitive disruption of Ca V β binding led to Ca V 1.2 degradation by exposing the channels to poly-ubiquitination. Notably, we demonstrated that the inverse relationship of reduced Gal-1 and increased Ca V 1.2 protein levels in arteries was associated with hypertension in hypertensive rats and patients, and Gal-1 deficiency induces higher blood pressure in mice due to up-regulated Ca V 1.2 protein level in arteries. To directly regulate blood pressure by targeting the Ca V 1.2-Gal-1 interaction, we administered Tat-e9c, a peptide that competed for binding of Gal-1, by a mini-osmotic pump and this specific disruption of Ca V 1.2-Gal-1 coupling increased smooth muscle Ca V 1.2 currents, induced larger arterial contraction and caused hypertension in rats. In contrasting experiments, over-expression of Gal-1 in smooth muscle by a

Setting realistic recovery targets for two interacting endangered species, sea otter and northern abalone.

PubMed

Chadès, Iadine; Curtis, Janelle M R; Martin, Tara G

2012-12-01

Failure to account for interactions between endangered species may lead to unexpected population dynamics, inefficient management strategies, waste of scarce resources, and, at worst, increased extinction risk. The importance of species interactions is undisputed, yet recovery targets generally do not account for such interactions. This shortcoming is a consequence of species-centered legislation, but also of uncertainty surrounding the dynamics of species interactions and the complexity of modeling such interactions. The northern sea otter (Enhydra lutris kenyoni) and one of its preferred prey, northern abalone (Haliotis kamtschatkana), are endangered species for which recovery strategies have been developed without consideration of their strong predator-prey interactions. Using simulation-based optimization procedures from artificial intelligence, namely reinforcement learning and stochastic dynamic programming, we combined sea otter and northern abalone population models with functional-response models and examined how different management actions affect population dynamics and the likelihood of achieving recovery targets for each species through time. Recovery targets for these interacting species were difficult to achieve simultaneously in the absence of management. Although sea otters were predicted to recover, achieving abalone recovery targets failed even when threats to abalone such as predation and poaching were reduced. A management strategy entailing a 50% reduction in the poaching of northern abalone was a minimum requirement to reach short-term recovery goals for northern abalone when sea otters were present. Removing sea otters had a marginally positive effect on the abalone population but only when we assumed a functional response with strong predation pressure. Our optimization method could be applied more generally to any interacting threatened or invasive species for which there are multiple conservation objectives. © 2012 Society for

GE781: a Monte Carlo package for fixed target experiments

NASA Astrophysics Data System (ADS)

Davidenko, G.; Funk, M. A.; Kim, V.; Kuropatkin, N.; Kurshetsov, V.; Molchanov, V.; Rud, S.; Stutte, L.; Verebryusov, V.; Zukanovich Funchal, R.

The Monte Carlo package for the fixed target experiment B781 at Fermilab, a third generation charmed baryon experiment, is described. This package is based on GEANT 3.21, ADAMO database and DAFT input/output routines.

IFPTarget: A Customized Virtual Target Identification Method Based on Protein-Ligand Interaction Fingerprinting Analyses.

PubMed

Li, Guo-Bo; Yu, Zhu-Jun; Liu, Sha; Huang, Lu-Yi; Yang, Ling-Ling; Lohans, Christopher T; Yang, Sheng-Yong

2017-07-24

Small-molecule target identification is an important and challenging task for chemical biology and drug discovery. Structure-based virtual target identification has been widely used, which infers and prioritizes potential protein targets for the molecule of interest (MOI) principally via a scoring function. However, current "universal" scoring functions may not always accurately identify targets to which the MOI binds from the retrieved target database, in part due to a lack of consideration of the important binding features for an individual target. Here, we present IFPTarget, a customized virtual target identification method, which uses an interaction fingerprinting (IFP) method for target-specific interaction analyses and a comprehensive index (Cvalue) for target ranking. Evaluation results indicate that the IFP method enables substantially improved binding pose prediction, and Cvalue has an excellent performance in target ranking for the test set. When applied to screen against our established target library that contains 11,863 protein structures covering 2842 unique targets, IFPTarget could retrieve known targets within the top-ranked list and identified new potential targets for chemically diverse drugs. IFPTarget prediction led to the identification of the metallo-β-lactamase VIM-2 as a target for quercetin as validated by enzymatic inhibition assays. This study provides a new in silico target identification tool and will aid future efforts to develop new target-customized methods for target identification.

Quantitative and Systems Pharmacology. 1. In Silico Prediction of Drug-Target Interactions of Natural Products Enables New Targeted Cancer Therapy.

PubMed

Fang, Jiansong; Wu, Zengrui; Cai, Chuipu; Wang, Qi; Tang, Yun; Cheng, Feixiong

2017-11-27

Natural products with diverse chemical scaffolds have been recognized as an invaluable source of compounds in drug discovery and development. However, systematic identification of drug targets for natural products at the human proteome level via various experimental assays is highly expensive and time-consuming. In this study, we proposed a systems pharmacology infrastructure to predict new drug targets and anticancer indications of natural products. Specifically, we reconstructed a global drug-target network with 7,314 interactions connecting 751 targets and 2,388 natural products and built predictive network models via a balanced substructure-drug-target network-based inference approach. A high area under receiver operating characteristic curve of 0.96 was yielded for predicting new targets of natural products during cross-validation. The newly predicted targets of natural products (e.g., resveratrol, genistein, and kaempferol) with high scores were validated by various literature studies. We further built the statistical network models for identification of new anticancer indications of natural products through integration of both experimentally validated and computationally predicted drug-target interactions of natural products with known cancer proteins. We showed that the significantly predicted anticancer indications of multiple natural products (e.g., naringenin, disulfiram, and metformin) with new mechanism-of-action were validated by various published experimental evidence. In summary, this study offers powerful computational systems pharmacology approaches and tools for the development of novel targeted cancer therapies by exploiting the polypharmacology of natural products.

A cryogenic target for Compton scattering experiments at HIγS

DOE PAGES

Kendellen, D. P.; Ahmed, M. W.; Baird, E.; ...

2016-10-06

We have developed a cryogenic target for use at the High Intensity γ-ray Source (HIγS). The target system is able to liquefy 4He at 4 K, hydrogen at 20 K, and deuterium at 23 K to fill a 0.3 L Kapton cell. Liquid temperatures and condenser pressures are recorded throughout each run in order to ensure that the target's areal density is known to ~1%. The target is being utilized in a series of experiments which probe the electromagnetic polarizabilities of the nucleon.

The muon component in extensive air showers and new p+C data in fixed target experiments

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

Meurer, C.; Bluemer, J.; Engel, R.

2007-03-19

One of the most promising approaches to determine the energy spectrum and composition of the cosmic rays with energies above 1015 eV is the measurement of the number of electrons and muons produced in extensive air showers (EAS). Therefore simulation of air showers using electromagnetic and hadronic interaction models are necessary. These simulations show uncertainties which come mainly from hadronic interaction models. One aim of this work is to specify the low energy hadronic interactions which are important for the muon production in EAS. Therefore we simulate extensive air showers with a modified version of the simulation package CORSIKA. Inmore » particular we investigate in detail the energy and the phase space regions of secondary particle production, which are most important for muon production. This phase space region is covered by fixed target experiments at CERN. In the second part of this work we present preliminary momentum spectra of secondary {pi}+ and {pi}- in p+C collisions at 12 GeV/c measured with the HARP spectrometer at the PS accelerator at CERN. In addition we use the new p+C NA49 data at 158 GeV/c to check the reliability of hadronic interaction models for muon production in EAS. Finally, possibilities to measure relevant quantities of hadron production in existing and planned accelerator experiments are discussed.« less

Exploring drug-target interaction networks of illicit drugs.

PubMed

Atreya, Ravi V; Sun, Jingchun; Zhao, Zhongming

2013-01-01

Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate their interaction patterns and potential secondary drugs that can aid future research and clinical care. In this study, we extracted 188 illicit substances and their related information from the DrugBank database. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an illicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target genes tend to cluster together and form four subnetworks, corresponding to four major medication categories: depressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second sublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of stimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we constructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs to the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs and bridge nodes, which might play important roles in the development and treatment of drug addiction. Among them, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including some results that are supported by previous studies. This study presents the first systematic review of the network

Exploring drug-target interaction networks of illicit drugs

PubMed Central

2013-01-01

Background Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate their interaction patterns and potential secondary drugs that can aid future research and clinical care. Results In this study, we extracted 188 illicit substances and their related information from the DrugBank database. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an illicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target genes tend to cluster together and form four subnetworks, corresponding to four major medication categories: depressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second sublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of stimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we constructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs to the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs and bridge nodes, which might play important roles in the development and treatment of drug addiction. Among them, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including some results that are supported by previous studies. Conclusions This study presents the first systematic

Interacting multiple model forward filtering and backward smoothing for maneuvering target tracking

NASA Astrophysics Data System (ADS)

Nandakumaran, N.; Sutharsan, S.; Tharmarasa, R.; Lang, Tom; McDonald, Mike; Kirubarajan, T.

2009-08-01

The Interacting Multiple Model (IMM) estimator has been proven to be effective in tracking agile targets. Smoothing or retrodiction, which uses measurements beyond the current estimation time, provides better estimates of target states. Various methods have been proposed for multiple model smoothing in the literature. In this paper, a new smoothing method, which involves forward filtering followed by backward smoothing while maintaining the fundamental spirit of the IMM, is proposed. The forward filtering is performed using the standard IMM recursion, while the backward smoothing is performed using a novel interacting smoothing recursion. This backward recursion mimics the IMM estimator in the backward direction, where each mode conditioned smoother uses standard Kalman smoothing recursion. Resulting algorithm provides improved but delayed estimates of target states. Simulation studies are performed to demonstrate the improved performance with a maneuvering target scenario. The comparison with existing methods confirms the improved smoothing accuracy. This improvement results from avoiding the augmented state vector used by other algorithms. In addition, the new technique to account for model switching in smoothing is a key in improving the performance.

Random walks on mutual microRNA-target gene interaction network improve the prediction of disease-associated microRNAs.

PubMed

Le, Duc-Hau; Verbeke, Lieven; Son, Le Hoang; Chu, Dinh-Toi; Pham, Van-Huy

2017-11-14

MicroRNAs (miRNAs) have been shown to play an important role in pathological initiation, progression and maintenance. Because identification in the laboratory of disease-related miRNAs is not straightforward, numerous network-based methods have been developed to predict novel miRNAs in silico. Homogeneous networks (in which every node is a miRNA) based on the targets shared between miRNAs have been widely used to predict their role in disease phenotypes. Although such homogeneous networks can predict potential disease-associated miRNAs, they do not consider the roles of the target genes of the miRNAs. Here, we introduce a novel method based on a heterogeneous network that not only considers miRNAs but also the corresponding target genes in the network model. Instead of constructing homogeneous miRNA networks, we built heterogeneous miRNA networks consisting of both miRNAs and their target genes, using databases of known miRNA-target gene interactions. In addition, as recent studies demonstrated reciprocal regulatory relations between miRNAs and their target genes, we considered these heterogeneous miRNA networks to be undirected, assuming mutual miRNA-target interactions. Next, we introduced a novel method (RWRMTN) operating on these mutual heterogeneous miRNA networks to rank candidate disease-related miRNAs using a random walk with restart (RWR) based algorithm. Using both known disease-associated miRNAs and their target genes as seed nodes, the method can identify additional miRNAs involved in the disease phenotype. Experiments indicated that RWRMTN outperformed two existing state-of-the-art methods: RWRMDA, a network-based method that also uses a RWR on homogeneous (rather than heterogeneous) miRNA networks, and RLSMDA, a machine learning-based method. Interestingly, we could relate this performance gain to the emergence of "disease modules" in the heterogeneous miRNA networks used as input for the algorithm. Moreover, we could demonstrate that RWRMTN is stable

3-D Modeling of Planar Target-Mount Perturbation Experiments on OMEGA

NASA Astrophysics Data System (ADS)

Collins, T. J. B.; Marshall, F. J.; Marozas, J. A.; Bonino, M. J.; Forties, R.; Goncharov, V. N.; Igumenshchev, I. V.; McKenty, P. W.; Smalyuk, V. A.

2008-11-01

OMEGA cryogenic targets are suspended in the target chamber using four spider silks attached to a C-shaped mount. The spider silks are typically composed of two entwined protein strands comparable to 1 μm in diameter. The silks and mount refract the incident laser light and cast shadows on the target surface. Experiments to measure the effects of the silks on target illumination have been performed in planar geometry using silks suspended parallel to a 20-μm-thick laser-driven target. The evolution of the surface perturbations introduced by the silks was measured using x-ray backlighting. The results of these experiments will be compared to simulations performed with DRACO, employing three-dimensional (3-D) planar hydrodynamics and a new 3-D refractive ray-trace package written specifically for this geometry. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-08NA28302.

Plant microRNA-Target Interaction Identification Model Based on the Integration of Prediction Tools and Support Vector Machine

PubMed Central

Meng, Jun; Shi, Lin; Luan, Yushi

2014-01-01

Background Confident identification of microRNA-target interactions is significant for studying the function of microRNA (miRNA). Although some computational miRNA target prediction methods have been proposed for plants, results of various methods tend to be inconsistent and usually lead to more false positive. To address these issues, we developed an integrated model for identifying plant miRNA–target interactions. Results Three online miRNA target prediction toolkits and machine learning algorithms were integrated to identify and analyze Arabidopsis thaliana miRNA-target interactions. Principle component analysis (PCA) feature extraction and self-training technology were introduced to improve the performance. Results showed that the proposed model outperformed the previously existing methods. The results were validated by using degradome sequencing supported Arabidopsis thaliana miRNA-target interactions. The proposed model constructed on Arabidopsis thaliana was run over Oryza sativa and Vitis vinifera to demonstrate that our model is effective for other plant species. Conclusions The integrated model of online predictors and local PCA-SVM classifier gained credible and high quality miRNA-target interactions. The supervised learning algorithm of PCA-SVM classifier was employed in plant miRNA target identification for the first time. Its performance can be substantially improved if more experimentally proved training samples are provided. PMID:25051153

Computational-experimental approach to drug-target interaction mapping: A case study on kinase inhibitors

PubMed Central

Ravikumar, Balaguru; Parri, Elina; Timonen, Sanna; Airola, Antti; Wennerberg, Krister

2017-01-01

Due to relatively high costs and labor required for experimental profiling of the full target space of chemical compounds, various machine learning models have been proposed as cost-effective means to advance this process in terms of predicting the most potent compound-target interactions for subsequent verification. However, most of the model predictions lack direct experimental validation in the laboratory, making their practical benefits for drug discovery or repurposing applications largely unknown. Here, we therefore introduce and carefully test a systematic computational-experimental framework for the prediction and pre-clinical verification of drug-target interactions using a well-established kernel-based regression algorithm as the prediction model. To evaluate its performance, we first predicted unmeasured binding affinities in a large-scale kinase inhibitor profiling study, and then experimentally tested 100 compound-kinase pairs. The relatively high correlation of 0.77 (p < 0.0001) between the predicted and measured bioactivities supports the potential of the model for filling the experimental gaps in existing compound-target interaction maps. Further, we subjected the model to a more challenging task of predicting target interactions for such a new candidate drug compound that lacks prior binding profile information. As a specific case study, we used tivozanib, an investigational VEGF receptor inhibitor with currently unknown off-target profile. Among 7 kinases with high predicted affinity, we experimentally validated 4 new off-targets of tivozanib, namely the Src-family kinases FRK and FYN A, the non-receptor tyrosine kinase ABL1, and the serine/threonine kinase SLK. Our sub-sequent experimental validation protocol effectively avoids any possible information leakage between the training and validation data, and therefore enables rigorous model validation for practical applications. These results demonstrate that the kernel-based modeling approach

Physics opportunities with a fixed target experiment at the LHC (AFTER@LHC)

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

Hadjidakis, Cynthia; Anselmino, Mauro; Arnaldi, R.

By extracting the beam with a bent crystal or by using an internal gas target, the multi-TeV proton and lead LHC beams allow one to perform the most energetic fixed-target experiments (AFTER@LHC) and to study p+p and p+A collisions at \\sqrt{s_NN}=115 GeV and Pb+p and Pb+A collisions at \\sqrt{s_NN}=72 GeV. Such studies would address open questions in the domain of the nucleon and nucleus partonic structure at high-x, quark-gluon plasma and, by using longitudinally or transversally polarised targets, spin physics. In this paper, we discuss the physics opportunities of a fixed-target experiment at the LHC and we report on themore » possible technical implementations of a high-luminosity experiment. We finally present feasibility studies for Drell-Yan, open heavy-flavour and quarkonium production, with an emphasis on high-x and spin physics.« less

Survey of beta-particle interaction experiments with asymmetric matter

NASA Astrophysics Data System (ADS)

Van Horn, J. David; Wu, Fei

2018-05-01

Asymmetry is a basic property found at multiple scales in the universe. Asymmetric molecular interactions are fundamental to the operation of biological systems in both signaling and structural roles. Other aspects of asymmetry are observed and useful in many areas of science and engineering, and have been studied since the discovery of chirality in tartrate salts. The observation of parity violation in beta decay provided some impetus for later experiments using asymmetric particles. Here we survey historical work and experiments related to electron (e-) or positron (e+) polarimetry and their interactions with asymmetric materials in gas, liquid and solid forms. Asymmetric interactions may be classified as: 1) stereorecognition, 2) stereoselection and 3) stereoinduction. These three facets of physical stereochemistry are unique but interrelated; and examples from chemistry and materials science illustrate these aspects. Experimental positron and electron interactions with asymmetric materials may be classified in like manner. Thus, a qualitative assessment of helical and polarized positron experiments with different forms of asymmetric matter from the past 40 years is presented, as well as recent experiments with left-hand and right-hand single crystal quartz and organic compounds. The purpose of this classification and review is to evaluate the field for potential new experiments and directions for positron (or electron) studies with asymmetric materials.

Solar array experiments on the SPHINX satellite. [Space Plasma High voltage INteraction eXperiment satellite

NASA Technical Reports Server (NTRS)

Stevens, N. J.

1974-01-01

The Space Plasma, High Voltage Interaction Experiment (SPHINX) is the name given to an auxiliary payload satellite scheduled to be launched in January 1974. The principal experiments carried on this satellite are specifically designed to obtain the engineering data on the interaction of high voltage systems with the space plasma. The classes of experiments are solar array segments, insulators, insulators with pin holes and conductors. The satellite is also carrying experiments to obtain flight data on three new solar array configurations: the edge illuminated-multijunction cells, the teflon encased cells, and the violet cells.

Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy.

PubMed

Efferth, Thomas; Koch, Egon

2011-01-01

Drugs derived from natural resources represent a significant segment of the pharmaceutical market as compared to randomly synthesized compounds. It is a goal of drug development programs to design selective ligands that act on single disease targets to obtain highly effective and safe drugs with low side effects. Although this strategy was successful for many new therapies, there is a marked decline in the number of new drugs introduced into clinical practice over the past decades. One reason for this failure may be due to the fact that the pathogenesis of many diseases is rather multi-factorial in nature and not due to a single cause. Phytotherapy, whose therapeutic efficacy is based on the combined action of a mixture of constituents, offers new treatment opportunities. Because of their biological defence function, plant secondary metabolites act by targeting and disrupting the cell membrane, by binding and inhibiting specific proteins or they adhere to or intercalate into RNA or DNA. Phytotherapeutics may exhibit pharmacological effects by the synergistic or antagonistic interaction of many phytochemicals. Mechanistic reasons for interactions are bioavailability, interference with cellular transport processes, activation of pro-drugs or deactivation of active compounds to inactive metabolites, action of synergistic partners at different points of the same signalling cascade (multi-target effects) or inhibition of binding to target proteins. "-Omics" technologies and systems biology may facilitate unravelling synergistic effects of herbal mixtures.

Measurement of electromagnetic pulses generated during interactions of high power lasers with solid targets

NASA Astrophysics Data System (ADS)

De Marco, M.; Krása, J.; Cikhardt, J.; Pfeifer, M.; Krouský, E.; Margarone, D.; Ahmed, H.; Borghesi, M.; Kar, S.; Giuffrida, L.; Vrana, R.; Velyhan, A.; Limpouch, J.; Korn, G.; Weber, S.; Velardi, L.; Delle Side, D.; Nassisi, V.; Ullschmied, J.

2016-06-01

A target irradiated with a high power laser pulse, blows off a large amount of charge and as a consequence the target itself becomes a generator of electromagnetic pulses (EMP) owing to high return current flowing to the ground through the target holder. The first measurement of the magnetic field induced by the neutralizing current reaching a value of a few kA was performed with the use of an inductive target probe at the PALS Laser Facility (Cikhardt et al. Rev. Sci. Instrum. 85 (2014) 103507). A full description of EMP generation should contain information on the spatial distribution and temporal variation of the electromagnetic field inside and outside of the interaction chamber. For this reason, we consider the interaction chamber as a resonant cavity in which different modes of EMP oscillate for hundreds of nanoseconds, until the EMP is transmitted outside through the glass windows and EM waves are attenuated. Since the experimental determination of the electromagnetic field distribution is limited by the number of employed antennas, a mapping of the electromagnetic field has to be integrated with numerical simulations. Thus, this work reports on a detailed numerical mapping of the electromagnetic field inside the interaction chamber at the PALS Laser Facility (covering a frequency spectrum from 100 MHz to 3 GHz) using the commercial code COMSOL Multiphysics 5.2. Moreover we carried out a comparison of the EMP generated in the parallelepiped-like interaction chamber used in the Vulcan Petawatt Laser Facility at the Rutherford Appleton Laboratory, against that produced in the spherical interaction chamber of PALS.

Target-object integration, attention distribution, and object orientation interactively modulate object-based selection.

PubMed

Al-Janabi, Shahd; Greenberg, Adam S

2016-10-01

The representational basis of attentional selection can be object-based. Various studies have suggested, however, that object-based selection is less robust than spatial selection across experimental paradigms. We sought to examine the manner by which the following factors might explain this variation: Target-Object Integration (targets 'on' vs. part 'of' an object), Attention Distribution (narrow vs. wide), and Object Orientation (horizontal vs. vertical). In Experiment 1, participants discriminated between two targets presented 'on' an object in one session, or presented as a change 'of' an object in another session. There was no spatial cue-thus, attention was initially focused widely-and the objects were horizontal or vertical. We found evidence of object-based selection only when targets constituted a change 'of' an object. Additionally, object orientation modulated the sign of object-based selection: We observed a same-object advantage for horizontal objects, but a same-object cost for vertical objects. In Experiment 2, an informative cue preceded a single target presented 'on' an object or as a change 'of' an object (thus, attention was initially focused narrowly). Unlike in Experiment 1, we found evidence of object-based selection independent of target-object integration. We again found that the sign of selection was modulated by the objects' orientation. This result may reflect a meridian effect, which emerged due to anisotropies in the cortical representations when attention is oriented endogenously. Experiment 3 revealed that object orientation did not modulate object-based selection when attention was oriented exogenously. Our findings suggest that target-object integration, attention distribution, and object orientation modulate object-based selection, but only in combination.

Design for Engaging Experience and Social Interaction

ERIC Educational Resources Information Center

Harteveld, Casper; ten Thij, Eleonore; Copier, Marinka

2011-01-01

One of the goals of game designers is to design for an engaging experience and for social interaction. The question is how. We know that games can be engaging and allow for social interaction, but how do we achieve this or even improve on it? This article provides an overview of several scientific approaches that deal with this question. It…

All-optical atom trap as a target for MOTRIMS-like collision experiments

NASA Astrophysics Data System (ADS)

Sharma, S.; Acharya, B. P.; De Silva, A. H. N. C.; Parris, N. W.; Ramsey, B. J.; Romans, K. L.; Dorn, A.; de Jesus, V. L. B.; Fischer, D.

2018-04-01

Momentum-resolved scattering experiments with laser-cooled atomic targets have been performed since almost two decades with magneto-optical trap recoil ion momentum spectroscopy (MOTRIMS) setups. Compared to experiments with gas-jet targets, MOTRIMS features significantly lower target temperatures allowing for an excellent recoil ion momentum resolution. However, the coincident and momentum-resolved detection of electrons was long rendered impossible due to incompatible magnetic field requirements. Here we report on an experimental approach which is based on an all-optical 6Li atom trap that—in contrast to magneto-optical traps—does not require magnetic field gradients in the trapping region. Atom temperatures of about 2 mK and number densities up to 109 cm-3 make this trap ideally suited for momentum-resolved electron-ion coincidence experiments. The overall configuration of the trap is very similar to conventional magneto-optical traps. It mainly requires small modifications of laser beam geometries and polarization which makes it easily implementable in other existing MOTRIMS experiments.

In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A

PubMed Central

Stoltenburg, Regina; Schubert, Thomas; Strehlitz, Beate

2015-01-01

A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment) is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for monitoring the aptamer selection progress. Structural investigations and sequence truncation experiments of the selected aptamer for Protein A led to the conclusion, that a stem-loop structure at its 5’-end including the 5’-primer binding site is essential for aptamer-target binding. Extensive interaction analyses between aptamer and Protein A were performed by methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based binding assays using fluorescence measurements. The binding of the aptamer to its target was thus investigated in assays with immobilization of one of the binding partners each, and with both binding partners in solution. Affinity constants were determined in the low micromolar to submicromolar range, increasing to the nanomolar range under the assumption of avidity. Protein A provides more than one binding site for the aptamer, which may overlap with the known binding sites for immunoglobulins. The aptamer binds specifically to both native and recombinant Protein A, but not to other immunoglobulin-binding proteins like Protein G and L. Cross specificity to other proteins was not found. The application of the aptamer is directed to Protein A detection or affinity purification. Moreover, whole cells of Staphylococcus aureus, presenting Protein A on the cell surface, could also be bound by the aptamer. PMID:26221730

In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A.

PubMed

Stoltenburg, Regina; Schubert, Thomas; Strehlitz, Beate

2015-01-01

A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment) is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for monitoring the aptamer selection progress. Structural investigations and sequence truncation experiments of the selected aptamer for Protein A led to the conclusion, that a stem-loop structure at its 5'-end including the 5'-primer binding site is essential for aptamer-target binding. Extensive interaction analyses between aptamer and Protein A were performed by methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based binding assays using fluorescence measurements. The binding of the aptamer to its target was thus investigated in assays with immobilization of one of the binding partners each, and with both binding partners in solution. Affinity constants were determined in the low micromolar to submicromolar range, increasing to the nanomolar range under the assumption of avidity. Protein A provides more than one binding site for the aptamer, which may overlap with the known binding sites for immunoglobulins. The aptamer binds specifically to both native and recombinant Protein A, but not to other immunoglobulin-binding proteins like Protein G and L. Cross specificity to other proteins was not found. The application of the aptamer is directed to Protein A detection or affinity purification. Moreover, whole cells of Staphylococcus aureus, presenting Protein A on the cell surface, could also be bound by the aptamer.

DrugECs: An Ensemble System with Feature Subspaces for Accurate Drug-Target Interaction Prediction

PubMed Central

Jiang, Jinjian; Wang, Nian; Zhang, Jun

2017-01-01

Background Drug-target interaction is key in drug discovery, especially in the design of new lead compound. However, the work to find a new lead compound for a specific target is complicated and hard, and it always leads to many mistakes. Therefore computational techniques are commonly adopted in drug design, which can save time and costs to a significant extent. Results To address the issue, a new prediction system is proposed in this work to identify drug-target interaction. First, drug-target pairs are encoded with a fragment technique and the software “PaDEL-Descriptor.” The fragment technique is for encoding target proteins, which divides each protein sequence into several fragments in order and encodes each fragment with several physiochemical properties of amino acids. The software “PaDEL-Descriptor” creates encoding vectors for drug molecules. Second, the dataset of drug-target pairs is resampled and several overlapped subsets are obtained, which are then input into kNN (k-Nearest Neighbor) classifier to build an ensemble system. Conclusion Experimental results on the drug-target dataset showed that our method performs better and runs faster than the state-of-the-art predictors. PMID:28744468

Ten years of experience from interactive ergonomics projects.

PubMed

Eklund, J; Karltun, J

2012-01-01

This paper highlights experiences from ergonomics projects, applying an interactive research approach. The aim of this paper is to summarise experiences from seven interactive ergonomics projects with the aim to improve ergonomics and organizational performance jointly. Results from these seven projects were analysed with a model for assessing sustainable change, including the factors active ownership, professional management, competent project leadership, and involved participants. All factors were found giving support to impact and sustainability of the change projects. However, the role of the researcher is difficult and demanding.

Targeting the Poor: Evidence from a Field Experiment in Indonesia

PubMed Central

Alatas, Vivi; Banerjee, Abhijit; Hanna, Rema; Olken, Benjamin A.; Tobias, Julia

2014-01-01

This paper reports an experiment in 640 Indonesian villages on three approaches to target the poor: proxy-means tests (PMT), where assets are used to predict consumption; community targeting, where villagers rank everyone from richest to poorest; and a hybrid. Defining poverty based on PPP$2 per-capita consumption, community targeting and the hybrid perform somewhat worse in identifying the poor than PMT, though not by enough to significantly affect poverty outcomes for a typical program. Elite capture does not explain these results. Instead, communities appear to apply a different concept of poverty. Consistent with this finding, community targeting results in higher satisfaction. PMID:25197099

Interactive Lecture Experiments in Large Introductory Physics Classes

NASA Astrophysics Data System (ADS)

Milner-Bolotin, Marina M.; Kotlicki, A.; Rieger, G.; Bates, F.; Moll, R.; McPhee, K.; Nashon, S.

2006-12-01

We describe Interactive Lecture Experiments (ILE), which build on Interactive Lecture Demonstrations proposed by Sokoloff and Thornton (2004) and extends it by providing students with the opportunity to analyze experiments demonstrated in the lecture outside of the classroom. Real time experimental data is collected, using Logger Pro combined with the digital video technology. This data is uploaded to the Internet and made available to the students for further analysis. Student learning is assessed in the following lecture using conceptual questions (clickers). The goal of this project is to use ILE to make large lectures more interactive and promote student interest in science, critical thinking and data analysis skills. We report on the systematic study conducted using the Colorado Learning Attitudes about Science Survey, Force Concept Inventory, open-ended physics problems and focus group interviews to determine the impact of ILE on student academic achievement, motivation and attitudes towards physics. Three sections of students (750 students) experienced four ILE experiments. The surveys were administered twice and academic results for students who experienced the ILE for a particular topic were compared to the students, from a different section, who did not complete the ILE for that topic. Additional qualitative data on students’ attitudes was collected using open ended survey questions and interviews. We will present preliminary conclusions about the role of ILEs as an effective pedagogy in large introductory physics courses. Sokoloff, D.R. and R.K. Thornton (2004). Interactive Lecture Demonstrations: Active Learning in Introductory Physics, J.Wiley & Sons, INC. Interactive Lecture Experiments: http://www.physics.ubc.ca/ year1lab/p100/LectureLabs/lectureLabs.html

Interactive Plasma Physics Education Using Data from Fusion Experiments

NASA Astrophysics Data System (ADS)

Calderon, Brisa; Davis, Bill; Zwicker, Andrew

2010-11-01

The Internet Plasma Physics Education Experience (IPPEX) website was created in 1996 to give users access to data from plasma and fusion experiments. Interactive material on electricity, magnetism, matter, and energy was presented to generate interest and prepare users to understand data from a fusion experiment. Initially, users were allowed to analyze real-time and archival data from the Tokamak Fusion Test Reactor (TFTR) experiment. IPPEX won numerous awards for its novel approach of allowing users to participate in ongoing research. However, the latest revisions of IPPEX were in 2001 and the interactive material is no longer functional on modern browsers. Also, access to real-time data was lost when TFTR was shut down. The interactive material on IPPEX is being rewritten in ActionScript3.0, and real-time and archival data from the National Spherical Tokamak Experiment (NSTX) will be made available to users. New tools like EFIT animations, fast cameras, and plots of important plasma parameters will be included along with an existing Java-based ``virtual tokamak.'' Screenshots from the upgraded website and future directions will be presented.

Membrane nanotubes facilitate long-distance interactions between natural killer cells and target cells

PubMed Central

Chauveau, Anne; Aucher, Anne; Eissmann, Philipp; Vivier, Eric; Davis, Daniel M.

2010-01-01

Membrane nanotubes are membranous tethers that physically link cell bodies over long distances. Here, we present evidence that nanotubes allow human natural killer (NK) cells to interact functionally with target cells over long distances. Nanotubes were formed when NK cells contacted target cells and moved apart. The frequency of nanotube formation was dependent on the number of receptor/ligand interactions and increased on NK cell activation. Most importantly, NK cell nanotubes contained a submicron scale junction where proteins accumulated, including DAP10, the signaling adaptor that associates with the activating receptor NKG2D, and MHC class I chain-related protein A (MICA), a cognate ligand for NKG2D, as occurs at close intercellular synapses between NK cells and target cells. Quantitative live-cell fluorescence imaging suggested that MICA accumulated at small nanotube synapses in sufficient numbers to trigger cell activation. In addition, tyrosine-phosphorylated proteins and Vav-1 accumulated at such junctions. Functionally, nanotubes could aid the lysis of distant target cells either directly or by moving target cells along the nanotube path into close contact for lysis via a conventional immune synapse. Target cells moving along the nanotube path were commonly polarized such that their uropods faced the direction of movement. This is the opposite polarization than for normal cell migration, implying that nanotubes can specifically drive target cell movement. Finally, target cells that remained connected to an NK cell by a nanotube were frequently lysed, whereas removing the nanotube using a micromanipulator reduced lysis of these target cells. PMID:20212116

Computational approach for elucidating interactions of cross-species miRNAs and their targets in Flaviviruses.

PubMed

Shinde, Santosh P; Banerjee, Amit Kumar; Arora, Neelima; Murty, U S N; Sripathi, Venkateswara Rao; Pal-Bhadra, Manika; Bhadra, Utpal

2015-03-01

Combating viral diseases has been a challenging task since time immemorial. Available molecular approaches are limited and not much effective for this daunting task. MicroRNA based therapies have shown promise in recent times. MicroRNAs are tiny non-coding RNAs that regulate translational repression of target mRNA in highly specific manner. In this study, we have determined the target regions for human and viral microRNAs in the conserved genomic regions of selected viruses of Flaviviridae family using miRanda and performed a comparative target selectivity analysis among them. Specific target regions were determined and they were compared extensively among themselves by exploring their position to determine the vicinity. Based on the multiplicity and cooperativity analysis, interaction maps were developed manually to represent the interactions between top-ranking miRNAs and genomes of the viruses considered in this study. Self-organizing map (SOM) was used to cluster the best-ranked microRNAs based on the vital physicochemical properties. This study will provide deep insight into the interrelation of the viral and human microRNAs interactions with the selected Flaviviridae genomes and will help to identify cross-species microRNA targets on the viral genome.

Track reconstruction in the emulsion-lead target of the OPERA experiment using the ESS microscope

NASA Astrophysics Data System (ADS)

Arrabito, L.; Bozza, C.; Buontempo, S.; Consiglio, L.; Cozzi, M.; D'Ambrosio, N.; DeLellis, G.; DeSerio, M.; Di Capua, F.; Di Ferdinando, D.; Di Marco, N.; Ereditato, A.; Esposito, L. S.; Fini, R. A.; Giacomelli, G.; Giorgini, M.; Grella, G.; Ieva, M.; Janicsko Csathy, J.; Juget, F.; Kreslo, I.; Laktineh, I.; Manai, K.; Mandrioli, G.; Marotta, A.; Migliozzi, P.; Monacelli, P.; Moser, U.; Muciaccia, M. T.; Pastore, A.; Patrizii, L.; Petukhov, Y.; Pistillo, C.; Pozzato, M.; Romano, G.; Rosa, G.; Russo, A.; Savvinov, N.; Schembri, A.; Scotto Lavina, L.; Simone, S.; Sioli, M.; Sirignano, C.; Sirri, G.; Strolin, P.; Tioukov, V.; Waelchli, T.

2007-05-01

The OPERA experiment, designed to conclusively prove the existence of νμ→ντ oscillations in the atmospheric sector, makes use of a massive lead-nuclear emulsion target to observe the appearance of ντ's in the CNGS νμ beam. The location and analysis of the neutrino interactions in quasi real-time required the development of fast computer-controlled microscopes able to reconstruct particle tracks with sub-micron precision and high efficiency at a speed of ~20 cm2/h. This paper describes the performance in particle track reconstruction of the European Scanning System, a novel automatic microscope for the measurement of emulsion films developed for OPERA.

An experiment with interactive planning models

NASA Technical Reports Server (NTRS)

Beville, J.; Wagner, J. H.; Zannetos, Z. S.

1970-01-01

Experiments on decision making in planning problems are described. Executives were tested in dealing with capital investments and competitive pricing decisions under conditions of uncertainty. A software package, the interactive risk analysis model system, was developed, and two controlled experiments were conducted. It is concluded that planning models can aid management, and predicted uses of the models are as a central tool, as an educational tool, to improve consistency in decision making, to improve communications, and as a tool for consensus decision making.

New prospects in fixed target searches for dark forces with the SeaQuest experiment at Fermilab

DOE PAGES

Gardner, S.; Holt, R. J.; Tadepalli, A. S.

2016-06-10

An intense 120 GeV proton beam incident on an extremely long iron target generates enormous numbers of light-mass particles that also decay within that target. If one of these particles decays to a final state with a hidden gauge boson, or if such a particle is produced as a result of the initial collision, then that weakly interacting hidden-sector particle may traverse the remainder of the target and be detected downstream through its possible decay to an e +e –, μ +μ –, or π +π – final state. These conditions can be realized through an extension of the SeaQuestmore » experiment at Fermilab, and in this initial investigation we consider how it can serve as an ultrasensitive probe of hidden vector gauge forces, both Abelian and non-Abelian. Here a light, weakly coupled hidden sector may well explain the dark matter established through astrophysical observations, and the proposed search can provide tangible evidence for its existence—or, alternatively, constrain a “sea” of possibilities.« less

Performance of a Liner-on-Target Injector for Staged Z-Pinch Experiments

NASA Astrophysics Data System (ADS)

Conti, F.; Valenzuela, J. C.; Narkis, J.; Krasheninnikov, I.; Beg, F.; Wessel, F. J.; Ruskov, E.; Rahman, H. U.; McGee, E.

2016-10-01

We present the design and characterization of a compact liner-on-target injector, used in the Staged Z-pinch experiments conducted on the UNR-NTF Zebra Facility. Previous experiments and analysis indicate that high-Z gas liners produce a uniform and efficient implosion on a low-Z target plasma. The liner gas shell is produced by an annular solenoid valve and a converging-diverging nozzle designed to achieve a collimated, supersonic, Mach-5 flow. The on-axis target is produced by a coaxial plasma gun, where a high voltage pulse is applied to ionize neutral gas and accelerate the plasma by the J-> × B-> force. Measurements of the liner and target dynamics, resolved by interferometry in space and time, fast imaging, and collection of the emitted light, are presented. The results are compared to the predictions from Computational Fluid Dynamics and MHD simulations that model the injector. Optimization of the design parameters, for upcoming Staged Z-pinch experiments, will be discussed. Advanced Research Projects Agency - Energy, DE-AR0000569.

Natural products used as a chemical library for protein-protein interaction targeted drug discovery.

PubMed

Jin, Xuemei; Lee, Kyungro; Kim, Nam Hee; Kim, Hyun Sil; Yook, Jong In; Choi, Jiwon; No, Kyoung Tai

2018-01-01

Protein-protein interactions (PPIs), which are essential for cellular processes, have been recognized as attractive therapeutic targets. Therefore, the construction of a PPI-focused chemical library is an inevitable necessity for future drug discovery. Natural products have been used as traditional medicines to treat human diseases for millennia; in addition, their molecular scaffolds have been used in diverse approved drugs and drug candidates. The recent discovery of the ability of natural products to inhibit PPIs led us to use natural products as a chemical library for PPI-targeted drug discovery. In this study, we collected natural products (NPDB) from non-commercial and in-house databases to analyze their similarities to small-molecule PPI inhibitors (iPPIs) and FDA-approved drugs by using eight molecular descriptors. Then, we evaluated the distribution of NPDB and iPPIs in the chemical space, represented by the molecular fingerprint and molecular scaffolds, to identify the promising scaffolds, which could interfere with PPIs. To investigate the ability of natural products to inhibit PPI targets, molecular docking was used. Then, we predicted a set of high-potency natural products by using the iPPI-likeness score based on a docking score-weighted model. These selected natural products showed high binding affinities to the PPI target, namely XIAP, which were validated in an in vitro experiment. In addition, the natural products with novel scaffolds might provide a promising starting point for further medicinal chemistry developments. Overall, our study shows the potency of natural products in targeting PPIs, which might help in the design of a PPI-focused chemical library for future drug discovery. Copyright © 2017 Elsevier Inc. All rights reserved.

Testing charged current quasi-elastic and multinucleon interaction models in the NEUT neutrino interaction generator with published datasets from the MiniBooNE and MINERνA experiments

NASA Astrophysics Data System (ADS)

Wilkinson, C.; Terri, R.; Andreopoulos, C.; Bercellie, A.; Bronner, C.; Cartwright, S.; de Perio, P.; Dobson, J.; Duffy, K.; Furmanski, A. P.; Haegel, L.; Hayato, Y.; Kaboth, A.; Mahn, K.; McFarland, K. S.; Nowak, J.; Redij, A.; Rodrigues, P.; Sánchez, F.; Schwehr, J. D.; Sinclair, P.; Sobczyk, J. T.; Stamoulis, P.; Stowell, P.; Tacik, R.; Thompson, L.; Tobayama, S.; Wascko, M. O.; Żmuda, J.

2016-04-01

There has been a great deal of theoretical work on sophisticated charged current quasi-elastic (CCQE) neutrino interaction models in recent years, prompted by a number of experimental results that measured unexpectedly large CCQE cross sections on nuclear targets. As the dominant interaction mode at T2K energies, and the signal process in oscillation analyses, it is important for the T2K experiment to include realistic CCQE cross section uncertainties in T2K analyses. To this end, T2K's Neutrino Interaction Working Group has implemented a number of recent models in NEUT, T2K's primary neutrino interaction event generator. In this paper, we give an overview of the models implemented and present fits to published νμ and ν¯ μ CCQE cross section measurements from the MiniBooNE and MINER ν A experiments. The results of the fits are used to select a default cross section model for future T2K analyses and to constrain the cross section uncertainties of the model. We find strong tension between datasets for all models investigated. Among the evaluated models, the combination of a modified relativistic Fermi gas with multinucleon CCQE-like interactions gives the most consistent description of the available data.

Why we interact: on the functional role of the striatum in the subjective experience of social interaction.

PubMed

Pfeiffer, Ulrich J; Schilbach, Leonhard; Timmermans, Bert; Kuzmanovic, Bojana; Georgescu, Alexandra L; Bente, Gary; Vogeley, Kai

2014-11-01

There is ample evidence that human primates strive for social contact and experience interactions with conspecifics as intrinsically rewarding. Focusing on gaze behavior as a crucial means of human interaction, this study employed a unique combination of neuroimaging, eye-tracking, and computer-animated virtual agents to assess the neural mechanisms underlying this component of behavior. In the interaction task, participants believed that during each interaction the agent's gaze behavior could either be controlled by another participant or by a computer program. Their task was to indicate whether they experienced a given interaction as an interaction with another human participant or the computer program based on the agent's reaction. Unbeknownst to them, the agent was always controlled by a computer to enable a systematic manipulation of gaze reactions by varying the degree to which the agent engaged in joint attention. This allowed creating a tool to distinguish neural activity underlying the subjective experience of being engaged in social and non-social interaction. In contrast to previous research, this allows measuring neural activity while participants experience active engagement in real-time social interactions. Results demonstrate that gaze-based interactions with a perceived human partner are associated with activity in the ventral striatum, a core component of reward-related neurocircuitry. In contrast, interactions with a computer-driven agent activate attention networks. Comparisons of neural activity during interaction with behaviorally naïve and explicitly cooperative partners demonstrate different temporal dynamics of the reward system and indicate that the mere experience of engagement in social interaction is sufficient to recruit this system. Copyright © 2014 Elsevier Inc. All rights reserved.

Micro-Environmental Signature of The Interactions between Druggable Target Protein, Dipeptidyl Peptidase-IV, and Anti-Diabetic Drugs.

PubMed

Chakraborty, Chiranjib; Mallick, Bidyut; Sharma, Ashish Ranjan; Sharma, Garima; Jagga, Supriya; Doss, C George Priya; Nam, Ju-Suk; Lee, Sang-Soo

2017-01-01

Druggability of a target protein depends on the interacting micro-environment between the target protein and drugs. Therefore, a precise knowledge of the interacting micro-environment between the target protein and drugs is requisite for drug discovery process. To understand such micro-environment, we performed in silico interaction analysis between a human target protein, Dipeptidyl Peptidase-IV (DPP-4), and three anti-diabetic drugs (saxagliptin, linagliptin and vildagliptin). During the theoretical and bioinformatics analysis of micro-environmental properties, we performed drug-likeness study, protein active site predictions, docking analysis and residual interactions with the protein-drug interface. Micro-environmental landscape properties were evaluated through various parameters such as binding energy, intermolecular energy, electrostatic energy, van der Waals'+H-bond+desolvo energy (E VHD ) and ligand efficiency (LE) using different in silico methods. For this study, we have used several servers and software, such as Molsoft prediction server, CASTp server, AutoDock software and LIGPLOT server. Through micro-environmental study, highest log P value was observed for linagliptin (1.07). Lowest binding energy was also observed for linagliptin with DPP-4 in the binding plot. We also identified the number of H-bonds and residues involved in the hydrophobic interactions between the DPP-4 and the anti-diabetic drugs. During interaction, two H-bonds and nine residues, two H-bonds and eleven residues as well as four H-bonds and nine residues were found between the saxagliptin, linagliptin as well as vildagliptin cases and DPP-4, respectively. Our in silico data obtained for drug-target interactions and micro-environmental signature demonstrates linagliptin as the most stable interacting drug among the tested anti-diabetic medicines.

Optimized hydrophobic interactions and hydrogen bonding at the target-ligand interface leads the pathways of drug-designing.

PubMed

Patil, Rohan; Das, Suranjana; Stanley, Ashley; Yadav, Lumbani; Sudhakar, Akulapalli; Varma, Ashok K

2010-08-16

Weak intermolecular interactions such as hydrogen bonding and hydrophobic interactions are key players in stabilizing energetically-favored ligands, in an open conformational environment of protein structures. However, it is still poorly understood how the binding parameters associated with these interactions facilitate a drug-lead to recognize a specific target and improve drugs efficacy. To understand this, comprehensive analysis of hydrophobic interactions, hydrogen bonding and binding affinity have been analyzed at the interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d] pyrimidine compounds. In-silico docking studies were performed, using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to investigate the role of ligand binding affinity at the hydrophobic pocket of c-Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA calculations were scrutinized to quantify the role of weak interactions in binding affinity and drug efficacy. The in-silico method has enabled us to reveal that a multi-targeted small molecule binds with low affinity to its respective targets. But its binding affinity can be altered by integrating the conformationally favored functional groups at the active site of the ligand-target interface. Docking studies of 4-amino-substituted molecules at the bioactive cascade of the c-Src and c-Abl have concluded that 3D structural folding at the protein-ligand groove is also a hallmark for molecular recognition of multi-targeted compounds and for predicting their biological activity. The results presented here demonstrate that hydrogen bonding and optimized hydrophobic interactions both stabilize the ligands at the target site, and help alter binding affinity and drug efficacy.

Optimized Hydrophobic Interactions and Hydrogen Bonding at the Target-Ligand Interface Leads the Pathways of Drug-Designing

PubMed Central

Stanley, Ashley; Yadav, Lumbani; Sudhakar, Akulapalli; Varma, Ashok K.

2010-01-01

Background Weak intermolecular interactions such as hydrogen bonding and hydrophobic interactions are key players in stabilizing energetically-favored ligands, in an open conformational environment of protein structures. However, it is still poorly understood how the binding parameters associated with these interactions facilitate a drug-lead to recognize a specific target and improve drugs efficacy. To understand this, comprehensive analysis of hydrophobic interactions, hydrogen bonding and binding affinity have been analyzed at the interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d] pyrimidine compounds. Methodology In-silico docking studies were performed, using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to investigate the role of ligand binding affinity at the hydrophobic pocket of c-Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA calculations were scrutinized to quantify the role of weak interactions in binding affinity and drug efficacy. Conclusions The in-silico method has enabled us to reveal that a multi-targeted small molecule binds with low affinity to its respective targets. But its binding affinity can be altered by integrating the conformationally favored functional groups at the active site of the ligand-target interface. Docking studies of 4-amino-substituted molecules at the bioactive cascade of the c-Src and c-Abl have concluded that 3D structural folding at the protein-ligand groove is also a hallmark for molecular recognition of multi-targeted compounds and for predicting their biological activity. The results presented here demonstrate that hydrogen bonding and optimized hydrophobic interactions both stabilize the ligands at the target site, and help alter binding affinity and drug efficacy. PMID:20808434

The Target Model of Strategic Interaction of Kazan Federal University and the Region in the Field of Education

ERIC Educational Resources Information Center

Gabdulchakov, Valerian F.

2016-01-01

The subject of the study in the article is conceptual basis of construction of the target model of interaction between University and region. Hence the topic of the article "the Target model of strategic interaction between the University and the region in the field of education." The objective was to design a target model of this…

Impact cratering in viscous targets - Laboratory experiments

NASA Technical Reports Server (NTRS)

Greeley, R.; Fink, J.; Snyder, D. B.; Gault, D. E.; Guest, J. E.; Schultz, P. H.

1980-01-01

To determine the effects of target yield strength and viscosity on the formation and morphology of Martian multilobed, slosh and rampart-type impact craters, 75 experiments in which target properties and impact energies were varied were carried out for high-speed motion picture observation in keeping with the following sequence: (1) projectile initial impact; (2) crater excavation and rise of ejecta plume; (3) formation of a transient central mound which generates a surge of material upon collapse that can partly override the plume deposit; and (4) oscillation of the central mound with progressively smaller surges of material leaving the crater. A dimensional analysis of the experimental results indicates that the dimensions of the central mound are proportional to (1) the energy of the impacting projectile and (2) to the inverse of both the yield strength and viscosity of the target material, and it is determined that extrapolation of these results to large Martian craters requires an effective surface layer viscosity of less than 10 to the 10th poise. These results may also be applicable to impacts on outer planet satellites composed of ice-silicate mixtures.

Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?

PubMed Central

Torres, Jaume; Surya, Wahyu; Li, Yan; Liu, Ding Xiang

2015-01-01

Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity. PMID:26053927

Application of a post-collisional-interaction distorted-wave model for (e, 2e) of some atomic targets and methane

NASA Astrophysics Data System (ADS)

Chinoune, M.; Houamer, S.; Dal Cappello, C.; Galstyan, A.

2016-10-01

Recently Isik et al (2016 J. Phys B: At. Mol. Opt. Phys. 49 065203) performed measurements of the triple differential cross sections (TDCSs) of methane by electron impact. Their data clearly show that post-collisional interaction (PCI) effects are present in the angular distributions of ejected electrons. A model describing the ejected electron by a distorted wave and including PCI is applied for the single ionization of atomic targets and for methane. Extensive comparisons between this model and other previous models are made with available experiments.

Increased subjective experience of non-target emotions in patients with frontotemporal dementia and Alzheimer’s disease

PubMed Central

Chen, Kuan-Hua; Lwi, Sandy J.; Hua, Alice Y.; Haase, Claudia M.; Miller, Bruce L.; Levenson, Robert W.

2017-01-01

Although laboratory procedures are designed to produce specific emotions, participants often experience mixed emotions (i.e., target and non-target emotions). We examined non-target emotions in patients with frontotemporal dementia (FTD), Alzheimer’s disease (AD), other neurodegenerative diseases, and healthy controls. Participants watched film clips designed to produce three target emotions. Subjective experience of non-target emotions was assessed and emotional facial expressions were coded. Compared to patients with other neurodegenerative diseases and healthy controls, FTD patients reported more positive and negative non-target emotions, whereas AD patients reported more positive non-target emotions. There were no group differences in facial expressions of non-target emotions. We interpret these findings as reflecting deficits in processing interoceptive and contextual information resulting from neurodegeneration in brain regions critical for creating subjective emotional experience. PMID:29457053

Penetration experiments in aluminum 1100 targets using soda-lime glass projectiles

NASA Technical Reports Server (NTRS)

Horz, Friedrich; Cintala, Mark J.; Bernhard, Ronald P.; Cardenas, Frank; Davidson, William E.; Haynes, Gerald; See, Thomas H.; Winkler, Jerry L.

1995-01-01

The cratering and penetration behavior of annealed aluminum 1100 targets, with thickness varied from several centimeters to ultra-thin foils less than 1 micrometer thick, were experimentally investigated using 3.2 mm diameter spherical soda-lime glass projectiles at velocities from 1 to 7 km/s. The objective was to establish quantitative, dimensional relationships between initial impact conditions (impact velocity, projectile diameter, and target thickness) and the diameter of the resulting crater or penetration hole. Such dimensional relationships and calibration experiments are needed to extract the diameters and fluxes of hypervelocity particles from space-exposed surfaces and to predict the performance of certain collisional shields. The cratering behavior of aluminum 1100 is fairly well predicted. However, crater depth is modestly deeper for our silicate impactors than the canonical value based on aluminum projectiles and aluminum 6061-T6 targets. The ballistic-limit thickness was also different. These differences attest to the great sensitivity of detailed crater geometry and penetration behavior on the physical properties of both the target and impactor. Each penetration experiment was equipped with a witness plate to monitor the nature of the debris plume emanating from the rear of the target. This plume consists of both projectile fragments and target debris. Both penetration hole and witness-plate spray patterns systematically evolve in response to projectile diameter/target thickness. The relative dimensions of the projectile and target totally dominate the experimental products documented in this report; impact velocity is an important contributor as well to the evolution of penetration holes, but is of subordinate significance for the witness-plate spray patterns.

Learner Agency and Its Effect on Spoken Interaction Time in the Target Language

ERIC Educational Resources Information Center

Knight, Janine; Barberà, Elena

2017-01-01

This paper presents the results of how four dyads in an online task-based synchronous computer-mediated (TB-SCMC) interaction event use their agency to carry out speaking tasks, and how their choices and actions affect time spent interacting in the target language. A case study approach was employed to analyse the language functions and cognitive…

Experiment research on infrared targets signature in mid and long IR spectral bands

NASA Astrophysics Data System (ADS)

Wang, Chensheng; Hong, Pu; Lei, Bo; Yue, Song; Zhang, Zhijie; Ren, Tingting

2013-09-01

Since the infrared imaging system has played a significant role in the military self-defense system and fire control system, the radiation signature of IR target becomes an important topic in IR imaging application technology. IR target signature can be applied in target identification, especially for small and dim targets, as well as the target IR thermal design. To research and analyze the targets IR signature systematically, a practical and experimental project is processed under different backgrounds and conditions. An infrared radiation acquisition system based on a MWIR cooled thermal imager and a LWIR cooled thermal imager is developed to capture the digital infrared images. Furthermore, some instruments are introduced to provide other parameters. According to the original image data and the related parameters in a certain scene, the IR signature of interested target scene can be calculated. Different background and targets are measured with this approach, and a comparison experiment analysis shall be presented in this paper as an example. This practical experiment has proved the validation of this research work, and it is useful in detection performance evaluation and further target identification research.

The Tn7 transposition regulator TnsC interacts with the transposase subunit TnsB and target selector TnsD

PubMed Central

Choi, Ki Young; Spencer, Jeanelle M.; Craig, Nancy L.

2014-01-01

The excision of transposon Tn7 from a donor site and its insertion into its preferred target site, attachment site attTn7, is mediated by four Tn7-encoded transposition proteins: TnsA, TnsB, TnsC, and TnsD. Transposition requires the assembly of a nucleoprotein complex containing all four Tns proteins and the DNA substrates, the donor site containing Tn7, and the preferred target site attTn7. TnsA and TnsB together form the heteromeric Tn7 transposase, and TnsD is a target-selecting protein that binds specifically to attTn7. TnsC is the key regulator of transposition, interacting with both the TnsAB transposase and TnsD-attTn7. We show here that TnsC interacts directly with TnsB, and identify the specific region of TnsC involved in the TnsB–TnsC interaction during transposition. We also show that a TnsC mutant defective in interaction with TnsB is defective for Tn7 transposition both in vitro and in vivo. Tn7 displays cis-acting target immunity, which blocks Tn7 insertion into a target DNA that already contains Tn7. We provide evidence that the direct TnsB–TnsC interaction that we have identified also mediates cis-acting Tn7 target immunity. We also show that TnsC interacts directly with the target selector protein TnsD. PMID:24982178

miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions.

PubMed

Chou, Chih-Hung; Shrestha, Sirjana; Yang, Chi-Dung; Chang, Nai-Wen; Lin, Yu-Ling; Liao, Kuang-Wen; Huang, Wei-Chi; Sun, Ting-Hsuan; Tu, Siang-Jyun; Lee, Wei-Hsiang; Chiew, Men-Yee; Tai, Chun-San; Wei, Ting-Yen; Tsai, Tzi-Ren; Huang, Hsin-Tzu; Wang, Chung-Yu; Wu, Hsin-Yi; Ho, Shu-Yi; Chen, Pin-Rong; Chuang, Cheng-Hsun; Hsieh, Pei-Jung; Wu, Yi-Shin; Chen, Wen-Liang; Li, Meng-Ju; Wu, Yu-Chun; Huang, Xin-Yi; Ng, Fung Ling; Buddhakosai, Waradee; Huang, Pei-Chun; Lan, Kuan-Chun; Huang, Chia-Yen; Weng, Shun-Long; Cheng, Yeong-Nan; Liang, Chao; Hsu, Wen-Lian; Huang, Hsien-Da

2018-01-04

MicroRNAs (miRNAs) are small non-coding RNAs of ∼ 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased ∼1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Network Analysis of Drug-target Interactions: A Study on FDA-approved New Molecular Entities Between 2000 to 2015.

PubMed

Lin, Hui-Heng; Zhang, Le-Le; Yan, Ru; Lu, Jin-Jian; Hu, Yuanjia

2017-09-25

The U.S. Food and Drug Administration (FDA) approves new drugs every year. Drug targets are some of the most important interactive molecules for drugs, as they have a significant impact on the therapeutic effects of drugs. In this work, we thoroughly analyzed the data of small molecule drugs approved by the U.S. FDA between 2000 and 2015. Specifically, we focused on seven classes of new molecular entity (NME) classified by the anatomic therapeutic chemical (ATC) classification system. They were NMEs and their corresponding targets for the cardiovascular system, respiratory system, nerve system, general anti-infective systemic, genito-urinary system and sex hormones, alimentary tract and metabolisms, and antineoplastic and immunomodulating agents. To study the drug-target interaction on the systems level, we employed network topological analysis and multipartite network projections. As a result, the drug-target relations of different kinds of drugs were comprehensively characterized and global pictures of drug-target, drug-drug, and target-target interactions were visualized and analyzed from the perspective of network models.

Numerical Modeling of Complex Targets for High-Energy- Density Experiments with Ion Beams and other Drivers

DOE PAGES

Koniges, Alice; Liu, Wangyi; Lidia, Steven; ...

2016-04-01

We explore the simulation challenges and requirements for experiments planned on facilities such as the NDCX-II ion accelerator at LBNL, currently undergoing commissioning. Hydrodynamic modeling of NDCX-II experiments include certain lower temperature effects, e.g., surface tension and target fragmentation, that are not generally present in extreme high-energy laser facility experiments, where targets are completely vaporized in an extremely short period of time. Target designs proposed for NDCX-II range from metal foils of order one micron thick (thin targets) to metallic foam targets several tens of microns thick (thick targets). These high-energy-density experiments allow for the study of fracture as wellmore » as the process of bubble and droplet formation. We incorporate these physics effects into a code called ALE-AMR that uses a combination of Arbitrary Lagrangian Eulerian hydrodynamics and Adaptive Mesh Refinement. Inclusion of certain effects becomes tricky as we must deal with non-orthogonal meshes of various levels of refinement in three dimensions. A surface tension model used for droplet dynamics is implemented in ALE-AMR using curvature calculated from volume fractions. Thick foam target experiments provide information on how ion beam induced shock waves couple into kinetic energy of fluid flow. Although NDCX-II is not fully commissioned, experiments are being conducted that explore material defect production and dynamics.« less

Coulomb Interactions in Hanbury Brown-Twiss Experiments with Electrons

ERIC Educational Resources Information Center

Shen, Kan

2009-01-01

This dissertation examines the effect of Coulomb interactions in Hanbury Brown-Twiss (HBT) type experiments with electrons. HBT experiments deal with intensity interference, which is related to the second-order correlation function of the particle field. This is an extension of the usual amplitude interference experiment, such as Young's…

First internal and external experiments at COSY Juelich

NASA Astrophysics Data System (ADS)

Prasuhn, D.; Maier, R.; Bechstedt, U.; Dietrich, J.; Hacker, U.; Martin, S.; Stockhorst, H.; Tölle, R.; Grzonka, D.; Nake, C.; Mosel, F.

1995-02-01

The inauguration of the cooler synchrotron COSY Jülich was celebrated on April 1st, 1993. After the first successful acceleration to proton momenta above 800 GeV/ c, beamtimes for experiments were scheduled in parallel to further machine development. The first experiment was the internal target experiment EDDA, which investigated the energy dependence of the p-p interaction. It makes use of a 3 × 4 μm 2 thin CH 2 fiber as an internal target. The thickness of the fiber is more than adequate to achieve high luminosities, so the intensity of the stored beam has to be reduced to 10 7 p. On the other hand, it is thin enough to achieve beam lifetimes of 3 s at 1.4 GeV/ c. Details of the target fabrication and the first experimental results will be discussed. Both external experimental facilities at COSY, the time-of-flight spectrometer, and the magnetic spectrometer BIG KARL use a liquid hydrogen (deuterium) target. The first experiments were carried out at proton energies between 300 MeV and 500 MeV. Also, these experimental data will be presented. Two further internal experiments are prepared for the installation into the COSY ring. The target for the first experiment is a gas-jet target, the second experiment uses ribbon targets for the interaction. The status of both experimental setups will be shown.

Atomic Force Microscopy Probing of Receptor–Nanoparticle Interactions for Riboflavin Receptor Targeted Gold–Dendrimer Nanocomposites

PubMed Central

2015-01-01

Riboflavin receptors are overexpressed in malignant cells from certain human breast and prostate cancers, and they constitute a group of potential surface markers important for cancer targeted delivery of therapeutic agents and imaging molecules. Here we report on the fabrication and atomic force microscopy (AFM) characterization of a core–shell nanocomposite consisting of a gold nanoparticle (AuNP) coated with riboflavin receptor-targeting poly(amido amine) dendrimer. We designed this nanocomposite for potential applications such as a cancer targeted imaging material based on its surface plasmon resonance properties conferred by AuNP. We employed AFM as a technique for probing the binding interaction between the nanocomposite and riboflavin binding protein (RfBP) in solution. AFM enabled precise measurement of the AuNP height distribution before (13.5 nm) and after chemisorption of riboflavin-conjugated dendrimer (AuNP–dendrimer; 20.5 nm). Binding of RfBP to the AuNP–dendrimer caused a height increase to 26.7 nm, which decreased to 22.8 nm when coincubated with riboflavin as a competitive ligand, supporting interaction of AuNP–dendrimer and its target protein. In summary, physical determination of size distribution by AFM imaging can serve as a quantitative approach to monitor and characterize the nanoscale interaction between a dendrimer-covered AuNP and target protein molecules in vitro. PMID:24571134

Obtaining control of cell surface functionalizations via Pre-targeting and Supramolecular host guest interactions

NASA Astrophysics Data System (ADS)

Rood, Mark T. M.; Spa, Silvia J.; Welling, Mick M.; Ten Hove, Jan Bart; van Willigen, Danny M.; Buckle, Tessa; Velders, Aldrik H.; van Leeuwen, Fijs W. B.

2017-01-01

The use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or “training” of cells to make them suitable for a specific application remains complex. By envisioning a chemical toolbox that enables specific, but straight-forward and generic cellular functionalization, we investigated how membrane-receptor (pre)targeting could be combined with supramolecular host-guest interactions based on β-cyclodextrin (CD) and adamantane (Ad). The feasibility of this approach was studied in cells with membranous overexpression of the chemokine receptor 4 (CXCR4). By combining specific targeting of CXCR4, using an adamantane (Ad)-functionalized Ac-TZ14011 peptide (guest; KD = 56 nM), with multivalent host molecules that entailed fluorescent β-CD-Poly(isobutylene-alt-maleic-anhydride)-polymers with different fluorescent colors and number of functionalities, host-guest cell-surface modifications could be studied in detail. A second set of Ad-functionalized entities enabled introduction of additional surface functionalities. In addition, the attraction between CD and Ad could be used to drive cell-cell interactions. Combined we have shown that supramolecular interactions, that are based on specific targeting of an overexpressed membrane-receptor, allow specific and stable, yet reversible, surface functionalization of viable cells and how this approach can be used to influence the interaction between cells and their surroundings.

Characterization of the fast electrons distribution produced in a high intensity laser target interaction

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

Westover, B.; Lawrence Livermore National Laboratory, Livermore, California 94550; Chen, C. D.

2014-03-15

Experiments on the Titan laser (∼150 J, 0.7 ps, 2 × 10{sup 20} W cm{sup −2}) at the Lawrence Livermore National Laboratory were carried out in order to study the properties of fast electrons produced by high-intensity, short pulse laser interacting with matter under conditions relevant to Fast Ignition. Bremsstrahlung x-rays produced by these fast electrons were measured by a set of compact filter-stack based x-ray detectors placed at three angles with respect to the target. The measured bremsstrahlung signal allows a characterization of the fast electron beam spectrum, conversion efficiency of laser energy into fast electron kinetic energy and angular distribution. A Monte Carlo codemore » Integrated Tiger Series was used to model the bremsstrahlung signal and infer a laser to fast electron conversion efficiency of 30%, an electron slope temperature of about 2.2 MeV, and a mean divergence angle of 39°. Simulations were also performed with the hybrid transport code ZUMA which includes fields in the target. In this case, a conversion efficiency of laser energy to fast electron energy of 34% and a slope temperature between 1.5 MeV and 4 MeV depending on the angle between the target normal direction and the measuring spectrometer are found. The observed temperature of the bremsstrahlung spectrum, and therefore the inferred electron spectrum are found to be angle dependent.« less

Interactions between target location and reward size modulate the rate of microsaccades in monkeys

PubMed Central

Tokiyama, Stefanie; Lisberger, Stephen G.

2015-01-01

We have studied how rewards modulate the occurrence of microsaccades by manipulating the size of an expected reward and the location of the cue that sets the expectations for future reward. We found an interaction between the size of the reward and the location of the cue. When monkeys fixated on a cue that signaled the size of future reward, the frequency of microsaccades was higher if the monkey expected a large vs. a small reward. When the cue was presented at a site in the visual field that was remote from the position of fixation, reward size had the opposite effect: the frequency of microsaccades was lower when the monkey was expecting a large reward. The strength of pursuit initiation also was affected by reward size and by the presence of microsaccades just before the onset of target motion. The gain of pursuit initiation increased with reward size and decreased when microsaccades occurred just before or after the onset of target motion. The effect of the reward size on pursuit initiation was much larger than any indirect effects reward might cause through modulation of the rate of microsaccades. We found only a weak relationship between microsaccade direction and the location of the exogenous cue relative to fixation position, even in experiments where the location of the cue indicated the direction of target motion. Our results indicate that the expectation of reward is a powerful modulator of the occurrence of microsaccades, perhaps through attentional mechanisms. PMID:26311180

Comparison of hydrodynamic simulations with two-shockwave drive target experiments

NASA Astrophysics Data System (ADS)

Karkhanis, Varad; Ramaprabhu, Praveen; Buttler, William

2015-11-01

We consider hydrodynamic continuum simulations to mimic ejecta generation in two-shockwave target experiments, where metallic surface is loaded by two successive shock waves. Time of second shock in simulations is determined to match experimental amplitudes at the arrival of the second shock. The negative Atwood number (A --> - 1) of ejecta simulations leads to two successive phase inversions of the interface corresponding to the passage of the shocks from heavy to light media in each instance. Metallic phase of ejecta (solid/liquid) depends on shock loading pressure in the experiment, and we find that hydrodynamic simulations quantify the liquid phase ejecta physics with a fair degree of accuracy, where RM instability is not suppressed by the strength effect. In particular, we find that our results of free surface velocity, maximum ejecta velocity, and maximum ejecta areal density are in excellent agreement with their experimental counterparts, as well as ejecta models. We also comment on the parametric space for hydrodynamic simulations in which they can be used to compare with the target experiments.

Inquiry style interactive virtual experiments: a case on circular motion

NASA Astrophysics Data System (ADS)

Zhou, Shaona; Han, Jing; Pelz, Nathaniel; Wang, Xiaojun; Peng, Liangyu; Xiao, Hua; Bao, Lei

2011-11-01

Interest in computer-based learning, especially in the use of virtual reality simulations is increasing rapidly. While there are good reasons to believe that technologies have the potential to improve teaching and learning, how to utilize the technology effectively in teaching specific content difficulties is challenging. To help students develop robust understandings of correct physics concepts, we have developed interactive virtual experiment simulations that have the unique feature of enabling students to experience force and motion via an analogue joystick, allowing them to feel the applied force and simultaneously see its effects. The simulations provide students learning experiences that integrate both scientific representations and low-level sensory cues such as haptic cues under a single setting. In this paper, we introduce a virtual experiment module on circular motion. A controlled study has been conducted to evaluate the impact of using this virtual experiment on students' learning of force and motion in the context of circular motion. The results show that the interactive virtual experiment method is preferred by students and is more effective in helping students grasp the physics concepts than the traditional education method such as problem-solving practices. Our research suggests that well-developed interactive virtual experiments can be useful tools in teaching difficult concepts in science.

Optimal de novo design of MRM experiments for rapid assay development in targeted proteomics.

PubMed

Bertsch, Andreas; Jung, Stephan; Zerck, Alexandra; Pfeifer, Nico; Nahnsen, Sven; Henneges, Carsten; Nordheim, Alfred; Kohlbacher, Oliver

2010-05-07

Targeted proteomic approaches such as multiple reaction monitoring (MRM) overcome problems associated with classical shotgun mass spectrometry experiments. Developing MRM quantitation assays can be time consuming, because relevant peptide representatives of the proteins must be found and their retention time and the product ions must be determined. Given the transitions, hundreds to thousands of them can be scheduled into one experiment run. However, it is difficult to select which of the transitions should be included into a measurement. We present a novel algorithm that allows the construction of MRM assays from the sequence of the targeted proteins alone. This enables the rapid development of targeted MRM experiments without large libraries of transitions or peptide spectra. The approach relies on combinatorial optimization in combination with machine learning techniques to predict proteotypicity, retention time, and fragmentation of peptides. The resulting potential transitions are scheduled optimally by solving an integer linear program. We demonstrate that fully automated construction of MRM experiments from protein sequences alone is possible and over 80% coverage of the targeted proteins can be achieved without further optimization of the assay.

Assessment of the significance of patent-derived information for the early identification of compound-target interaction hypotheses.

PubMed

Senger, Stefan

2017-04-21

Patents are an important source of information for effective decision making in drug discovery. Encouragingly, freely accessible patent-chemistry databases are now in the public domain. However, at present there is still a wide gap between relatively low coverage-high quality manually-curated data sources and high coverage data sources that use text mining and automated extraction of chemical structures. To secure much needed funding for further research and an improved infrastructure, hard evidence is required to demonstrate the significance of patent-derived information in drug discovery. Surprisingly little such evidence has been reported so far. To address this, the present study attempts to quantify the relevance of patents for formulating and substantiating hypotheses for compound-target interactions. A manually-curated set of 130 compound-target interaction pairs annotated with what are considered to be the earliest patent and publication has been produced. The analysis of this set revealed that in stark contrast to what has been reported for novel chemical structures, only about 10% of the compound-target interaction pairs could be found in publications in the scientific literature within one year of being reported in patents. The average delay across all interaction pairs is close to 4 years. In an attempt to benchmark current capabilities, it was also examined how much of the benefit of using patent-derived information can be retained when a bioannotated version of SureChEMBL is used as secondary source for the patent literature. Encouragingly, this approach found the patents in the annotated set for 72% of the compound-target interaction pairs. Similarly, the effect of using the bioactivity database ChEMBL as secondary source for the scientific literature was studied. Here, the publications from the annotated set were only found for 46% of the compound-target interaction pairs. Patent-derived information is a significant enabler for formulating compound-target

Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

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

Dudás, József, E-mail: jozsef.dudas@i-med.ac.at; Fullár, Alexandra, E-mail: fullarsz@gmail.com; 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest

Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factormore » κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells.« less

Efficient monoenergetic proton beam from ultra-fast laser interaction with nanostructured targets

NASA Astrophysics Data System (ADS)

Fazeli, R.

2018-03-01

The broad energy spectrum of laser-accelerated proton beams is the most important difficulty associated with such particle sources on the way to future applications such as medical therapy, proton imaging, inertial fusion, and high-energy physics. The generation of proton beams with enhanced monoenergetic features through an ultra-intense laser interaction with optimized nanostructured targets is reported. Targets were irradiated by 40 fs laser pulses of intensity 5.5 ×1020 W c m -2 and wavelength 1 μm. The results of multi-parametric Particle-in-Cell calculations showed that proton beams with considerably reduced energy spread can be obtained by using the proposed nanostructured target. At optimized target dimensions, the proton spectrum was found to exhibit a narrow peak at about 63 MeV with a relative energy spread of ΔE /Epeak˜ 5 % which is efficiently lower than what is expected for unstructured double layer targets (˜70%).

Pair production by high intensity picosecond laser interacting with thick solid target at XingGuangIII

NASA Astrophysics Data System (ADS)

Wu, Yuchi; Dong, Kegong; Yan, Yonghong; Zhu, Bin; Zhang, Tiankui; Chen, Jia; Yu, Minghai; Tan, Fang; Wang, Shaoyi; Han, Dan; Lu, Feng; Gu, Yuqiu

2017-06-01

An experiment for pair production by high intensity laser irradiating thick solid targets is present. The experiment used picosecond beam of the XingGuangIII laser facility, with intensities up to several 1019 W/cm2, pulse durations about 0.8 ps and laser energies around 120 J. Pairs were generated from 1 mm-thick tantalum disk targets with different diameters from 1 mm to 10 mm. Energy spectra of hot electron from targetrear surface represent a Maxwellian distribution and obey a scaling of ∼(Iλ2)0.5. Large quantity of positrons were observed at the target rear normal direction with a yield up to 2.8 × 109 e+/sr. Owing to the target rear surface sheath field, the positrons behave as a quasi-monoenergetic beam with peak energy of several MeV. Our experiment shows that the peak energy of positron beam is inversely proportional to the target diameter.

Bypassing Protein Corona Issue on Active Targeting: Zwitterionic Coatings Dictate Specific Interactions of Targeting Moieties and Cell Receptors.

PubMed

Safavi-Sohi, Reihaneh; Maghari, Shokoofeh; Raoufi, Mohammad; Jalali, Seyed Amir; Hajipour, Mohammad J; Ghassempour, Alireza; Mahmoudi, Morteza

2016-09-07

Surface functionalization strategies for targeting nanoparticles (NP) to specific organs, cells, or organelles, is the foundation for new applications of nanomedicine to drug delivery and biomedical imaging. Interaction of NPs with biological media leads to the formation of a biomolecular layer at the surface of NPs so-called as "protein corona". This corona layer can shield active molecules at the surface of NPs and cause mistargeting or unintended scavenging by the liver, kidney, or spleen. To overcome this corona issue, we have designed biotin-cysteine conjugated silica NPs (biotin was employed as a targeting molecule and cysteine was used as a zwitterionic ligand) to inhibit corona-induced mistargeting and thus significantly enhance the active targeting capability of NPs in complex biological media. To probe the targeting yield of our engineered NPs, we employed both modified silicon wafer substrates with streptavidin (i.e., biotin receptor) to simulate a target and a cell-based model platform using tumor cell lines that overexpress biotin receptors. In both cases, after incubation with human plasma (thus forming a protein corona), cellular uptake/substrate attachment of the targeted NPs with zwitterionic coatings were significantly higher than the same NPs without zwitterionic coating. Our results demonstrated that NPs with a zwitterionic surface can considerably facilitate targeting yield of NPs and provide a promising new type of nanocarriers in biological applications.

Efficient visualization of high-throughput targeted proteomics experiments: TAPIR.

PubMed

Röst, Hannes L; Rosenberger, George; Aebersold, Ruedi; Malmström, Lars

2015-07-15

Targeted mass spectrometry comprises a set of powerful methods to obtain accurate and consistent protein quantification in complex samples. To fully exploit these techniques, a cross-platform and open-source software stack based on standardized data exchange formats is required. We present TAPIR, a fast and efficient Python visualization software for chromatograms and peaks identified in targeted proteomics experiments. The input formats are open, community-driven standardized data formats (mzML for raw data storage and TraML encoding the hierarchical relationships between transitions, peptides and proteins). TAPIR is scalable to proteome-wide targeted proteomics studies (as enabled by SWATH-MS), allowing researchers to visualize high-throughput datasets. The framework integrates well with existing automated analysis pipelines and can be extended beyond targeted proteomics to other types of analyses. TAPIR is available for all computing platforms under the 3-clause BSD license at https://github.com/msproteomicstools/msproteomicstools. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Intermolecular interaction of thiosemicarbazone derivatives to solvents and a potential Aedes aegypti target

NASA Astrophysics Data System (ADS)

da Silva, João Bosco P.; Hallwass, Fernando; da Silva, Aluizio G.; Moreira, Diogo Rodrigo; Ramos, Mozart N.; Espíndola, José Wanderlan P.; de Oliveira, Ana Daura T.; Brondani, Dalci José; Leite, Ana Cristina L.; Merz, Kenneth M.

2015-08-01

DFT calculations were used to access information about structure, energy and electronic properties of series of phenyl- and phenoxymethyl-(thio)semicarbazone derivatives with demonstrated activity against the larvae of Aedes aegypti in stage L4. The way as the thiosemicarbazone derivatives can interact with solvents like DMSO and water were analyzed from the comparison between calculated and experimental 1H NMR chemical shifts. The evidences of thiosemicarbazone derivatives making H-bond interaction to solvent have provide us insights on how they can interact with a potential A. aegypti's biological target, the Sterol Carrier Protein-2.

Interaction of Myosin Phosphatase Target Subunit (MYPT1) with Myosin Phosphatase-RhoA Interacting Protein (MRIP): A Role of Glutamic Acids in the Interaction.

PubMed

Lee, Eunhee; Stafford, Walter F

2015-01-01

Scaffold proteins bind to and functionally link protein members of signaling pathways. Interaction of the scaffold proteins, myosin phosphatase target subunit (MYPT1) and myosin phosphatase-RhoA interacting protein (MRIP), causes co-localization of myosin phosphatase and RhoA to actomyosin. To examine biophysical properties of interaction of MYPT1 with MRIP, we employed analytical ultracentrifugation and surface plasmon resonance. In regard to MRIP, its residues 724-837 are sufficient for the MYPT1/MRIP interaction. Moreover, MRIP binds to MYPT1 as either a monomer or a dimer. With respect to MYPT1, its leucine repeat region, LR (residues 991-1030) is sufficient to account for the MYPT1/MRIP interaction. Furthermore, point mutations that replace glutamic acids 998-1000 within LR reduced the binding affinity toward MRIP. This suggests that the glutamic acids of MYPT1 play an important role in the interaction.

The role of experience in location estimation: Target distributions shift location memory biases.

PubMed

Lipinski, John; Simmering, Vanessa R; Johnson, Jeffrey S; Spencer, John P

2010-04-01

Research based on the Category Adjustment model concluded that the spatial distribution of target locations does not influence location estimation responses [Huttenlocher, J., Hedges, L., Corrigan, B., & Crawford, L. E. (2004). Spatial categories and the estimation of location. Cognition, 93, 75-97]. This conflicts with earlier results showing that location estimation is biased relative to the spatial distribution of targets [Spencer, J. P., & Hund, A. M. (2002). Prototypes and particulars: Geometric and experience-dependent spatial categories. Journal of Experimental Psychology: General, 131, 16-37]. Here, we resolve this controversy by using a task based on Huttenlocher et al. (Experiment 4) with minor modifications to enhance our ability to detect experience-dependent effects. Results after the first block of trials replicate the pattern reported in Huttenlocher et al. After additional experience, however, participants showed biases that significantly shifted according to the target distributions. These results are consistent with the Dynamic Field Theory, an alternative theory of spatial cognition that integrates long-term memory traces across trials relative to the perceived structure of the task space. Copyright 2009 Elsevier B.V. All rights reserved.

Transfer Orbit Plasma Interaction Experiment (TROPIX)

NASA Astrophysics Data System (ADS)

Hickman, Mark

Viewgraphs on the Transfer Orbit Plasma Interaction Experiment (TROPIX) are presented. Objectives of this research are (1) to map the charged particles in Earth's magnetosphere from LEO to GEO at high inclinations; (2) to measure plasma current collection and resulting shifts in vehicle electrical potential from LEO to GEO across range of orbital inclinations; (3) to study spacecraft interaction with plasma environment using solar electric propulsion (SEP) thrusters as plasma contactors; (4) to measure array degradation over mission duration; (5) to evaluate the potential of various microelectronics, spacecraft components, and instruments for future space missions; and (6) to demonstrate SEP technology applied to a flight vehicle. An overview of TROPIX is presented.

Simulations of beam-matter interaction experiments at the CERN HiRadMat facility and prospects of high-energy-density physics research.

PubMed

Tahir, N A; Burkart, F; Shutov, A; Schmidt, R; Wollmann, D; Piriz, A R

2014-12-01

In a recent publication [Schmidt et al., Phys. Plasmas 21, 080701 (2014)], we reported results on beam-target interaction experiments that have been carried out at the CERN HiRadMat (High Radiation to Materials) facility using extended solid copper cylindrical targets that were irradiated with a 440-GeV proton beam delivered by the Super Proton Synchrotron (SPS). On the one hand, these experiments confirmed the existence of hydrodynamic tunneling of the protons that leads to substantial increase in the range of the protons and the corresponding hadron shower in the target, a phenomenon predicted by our previous theoretical investigations [Tahir et al., Phys. Rev. ST Accel. Beams 25, 051003 (2012)]. On the other hand, these experiments demonstrated that the beam heated part of the target is severely damaged and is converted into different phases of high energy density (HED) matter, as suggested by our previous theoretical studies [Tahir et al., Phys. Rev. E 79, 046410 (2009)]. The latter confirms that the HiRadMat facility can be used to study HED physics. In the present paper, we give details of the numerical simulations carried out to understand the experimental measurements. These include the evolution of the physical parameters, for example, density, temperature, pressure, and the internal energy in the target, during and after the irradiation. This information is important in order to determine the region of the HED phase diagram that can be accessed in such experiments. These simulations have been done using the energy deposition code fluka and a two-dimensional hydrodynamic code, big2, iteratively.

Cavitation Damage Experiments for Mercury Spallation Targets At the LANSCE WNR in 2008

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

Riemer, Bernie; Wendel, Mark W; Felde, David K

2010-01-01

Proton beam experiments investigating cavitation damage in short pulse mercury spallation targets were performed at LANSCE WNR in July of 2008. They included two main areas for investigation: damage dependence on mercury velocity using geometry more prototypic to the SNS target than previously employed and damage dependence on incident proton beam flux intensity. The flow dependence experiment employed six test targets with mercury velocity in the channel ranging from 0 to more than 4 m/s. Each was hit with 100 WNR beam pulses with peak proton flux equivalent to that of SNS operating at 2.7 MW. Damage dependence on incidentmore » proton beam flux intensity was also investigated with three intensity levels used on simple rectangular shaped targets without mercury flow. Intensity variation was imposed by focusing the beam differently while maintaining protons per pulse. This kept total energy deposited in each target constant. A fourth test target was hit with various beams: constant protons and varied spot size; constant spot size and varied protons. No damage will be assessed in this case. Instead, acoustic emissions associated with cavitation collapse were measured by laser Doppler vibrometer (LDV) from readings of exterior vessel motions as well as by mercury wetted acoustic transducers. This paper will provide a description of the experiment and present available results. Damage assessment will require several months before surface analysis can be completed and was not available in time for IWSMT-9.« less

A polarized atomic-beam target for COSY-Jülich

NASA Astrophysics Data System (ADS)

Eversheim, P. D.; Altmeier, M.; Felden, O.; Glende, M.; Walker, M.; Hiemer, A.; Gebel, R.

1998-01-01

An atomic-beam target (ABT) for the EDDA experiment has been built in Bonn and was tested for the very first time at the cooler synchrotron COSY. The ABT differs from the polarized colliding-beams ion source for COSY in the DC-operation of the dissociator and the use of permanent 6-pole magnets. At present the beam optics of the ABT is set-up for maximum density in the interaction zone, but for target-cell operation it can be modified to give maximum intensity. The modular concept of this atomic ground-state target allows to provide all vector- (and tensor) polarizations for protons and deuterons, respectively. Up to now the polarization of the atomic-beam could be verified by the EDDA experiment to be ≳80% with a density in the interaction zone of ≳1011atoms/cm2.

Interaction of the high energy deuterons with the graphite target in the plasma focus devices based on Lee model

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

Akel, M., E-mail: pscientific2@aec.org.sy; Alsheikh Salo, S.; Ismael, Sh.

2014-07-15

Numerical experiments are systematically carried out using the Lee model code extended to compute the ion beams on various plasma focus devices operated with Deuterium gas. The deuteron beam properties of the plasma focus are studied for low and high energy plasma focus device. The energy spectral distribution for deuteron ions ejected from the pinch plasma is calculated and the ion numbers with energy around 1 MeV is then determined. The deuteron–graphite target interaction is studied for different conditions. The yield of the reaction {sup 12}C(d,n){sup 13}N and the induced radioactivity for one and multi shots plasma focus devices in themore » graphite solid target is investigated. Our results present the optimized high energy repetitive plasma focus devices as an alternative to accelerators for the production of {sup 13}N short lived radioisotopes. However, technical challenges await solutions on two fronts: (a) operation of plasma focus machines at high rep rates for a sufficient period of time (b) design of durable targets that can take the thermal load.« less

RISC-Target Interaction: Cleavage and Translational Suppression

PubMed Central

van den Berg, Arjen; Mols, Johann; Han, Jiahuai

2008-01-01

Summary Small RNA molecules have been known and utilized to suppress gene expression for more than a decade. The discovery that these small RNA molecules are endogenously expressed in many organisms and have a critical role in controlling gene expression have led to the arising of a whole new field of research. Termed small interfering RNA (siRNA) or microRNA (miRNA) these ~22 nt RNA molecules have the capability to suppress gene expression through various mechanisms once they are incorporated in the multi-protein RNA-Induced Silencing Complex (RISC) and interact with their target mRNA. This review introduces siRNAs and microRNAs in a historical perspective and focuses on the key molecules in RISC, structural properties and mechanisms underlying the process of small RNA regulated post-transcriptional suppression of gene expression. PMID:18692607

Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets

PubMed Central

Mohan, Nimmy; AP, Sudheesh; Francis, Nimmy; Anderson, Richard; Laishram, Rakesh S.

2015-01-01

Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3′-end processing. PMID:26138484

Legislative, educational, policy and other interventions targeting physicians' interaction with pharmaceutical companies: a systematic review.

PubMed

Alkhaled, Lina; Kahale, Lara; Nass, Hala; Brax, Hneine; Fadlallah, Racha; Badr, Kamal; Akl, Elie A

2014-07-01

Pharmaceutical company representatives likely influence the prescribing habits and professional behaviour of physicians. The objective of this study was to systematically review the effects of interventions targeting practising physicians' interactions with pharmaceutical companies. We included observational studies, non-randomised controlled trials (non-RCTs) and RCTs evaluating legislative, educational, policy or other interventions targeting the interactions between physicians and pharmaceutical companies. The search strategy included an electronic search of MEDLINE and EMBASE. Two reviewers performed duplicate and independent study selection, data abstraction and assessment of risk of bias. We assessed the risk of bias in each included study. We summarised the findings narratively because the nature of the data did not allow a meta-analysis to be conducted. We assessed the quality of evidence by outcome using the GRADE methodology. Of 11 189 identified citations, one RCT and three observational studies met the eligibility criteria. All four studies specifically targeted one type of interaction with pharmaceutical companies, that is, interactions with drug representatives. The RCT provided moderate quality evidence of no effect of a 'collaborative approach' between the pharmaceutical industry and a health authority. The three observational studies provided low quality evidence suggesting a positive effect of policies aiming to reduce interaction between physicians and pharmaceutical companies (by restricting free samples, promotional material, and meetings with pharmaceutical company representatives) on prescription behaviour. We identified too few studies to allow strong conclusions. Available evidence suggests a potential impact of policies aiming to reduce interaction between physicians and drug representatives on physicians' prescription behaviour. We found no evidence concerning interventions affecting other types of interaction with pharmaceutical

The Plasma Interaction Experiment (PIX) description and test program. [electrometers

NASA Technical Reports Server (NTRS)

Ignaczak, L. R.; Haley, F. A.; Domino, E. J.; Culp, D. H.; Shaker, F. J.

1978-01-01

The plasma interaction experiment (PIX) is a battery powered preprogrammed auxiliary payload on the LANDSAT-C launch. This experiment is part of a larger program to investigate space plasma interactions with spacecraft surfaces and components. The varying plasma densities encountered during available telemetry coverage periods are deemed sufficient to determine first order interactions between the space plasma environment and the biased experimental surfaces. The specific objectives of the PIX flight experiment are to measure the plasma coupling current and the negative voltage breakdown characteristics of a solar array segment and a gold plated steel disk. Measurements will be made over a range of surface voltages up to plus or minus kilovolt. The orbital environment will provide a range of plasma densities. The experimental surfaces will be voltage biased in a preprogrammed step sequence to optimize the data returned for each plasma region and for the available telemetry coverage.

Injector design for liner-on-target gas-puff experiments

NASA Astrophysics Data System (ADS)

Valenzuela, J. C.; Krasheninnikov, I.; Conti, F.; Wessel, F.; Fadeev, V.; Narkis, J.; Ross, M. P.; Rahman, H. U.; Ruskov, E.; Beg, F. N.

2017-11-01

We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ˜1 cm radius gas profile that satisfies the theoretical requirement for best performance on ˜1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.

Injector design for liner-on-target gas-puff experiments.

PubMed

Valenzuela, J C; Krasheninnikov, I; Conti, F; Wessel, F; Fadeev, V; Narkis, J; Ross, M P; Rahman, H U; Ruskov, E; Beg, F N

2017-11-01

We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ∼1 cm radius gas profile that satisfies the theoretical requirement for best performance on ∼1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.

Predicting drug-target interactions by dual-network integrated logistic matrix factorization

NASA Astrophysics Data System (ADS)

Hao, Ming; Bryant, Stephen H.; Wang, Yanli

2017-01-01

In this work, we propose a dual-network integrated logistic matrix factorization (DNILMF) algorithm to predict potential drug-target interactions (DTI). The prediction procedure consists of four steps: (1) inferring new drug/target profiles and constructing profile kernel matrix; (2) diffusing drug profile kernel matrix with drug structure kernel matrix; (3) diffusing target profile kernel matrix with target sequence kernel matrix; and (4) building DNILMF model and smoothing new drug/target predictions based on their neighbors. We compare our algorithm with the state-of-the-art method based on the benchmark dataset. Results indicate that the DNILMF algorithm outperforms the previously reported approaches in terms of AUPR (area under precision-recall curve) and AUC (area under curve of receiver operating characteristic) based on the 5 trials of 10-fold cross-validation. We conclude that the performance improvement depends on not only the proposed objective function, but also the used nonlinear diffusion technique which is important but under studied in the DTI prediction field. In addition, we also compile a new DTI dataset for increasing the diversity of currently available benchmark datasets. The top prediction results for the new dataset are confirmed by experimental studies or supported by other computational research.

Statistical results on restorative dentistry experiments: effect of the interaction between main variables

PubMed Central

CAVALCANTI, Andrea Nóbrega; MARCHI, Giselle Maria; AMBROSANO, Gláucia Maria Bovi

2010-01-01

Statistical analysis interpretation is a critical field in scientific research. When there is more than one main variable being studied in a research, the effect of the interaction between those variables is fundamental on experiments discussion. However, some doubts can occur when the p-value of the interaction is greater than the significance level. Objective To determine the most adequate interpretation for factorial experiments with p-values of the interaction nearly higher than the significance level. Materials and methods The p-values of the interactions found in two restorative dentistry experiments (0.053 and 0.068) were interpreted in two distinct ways: considering the interaction as not significant and as significant. Results Different findings were observed between the two analyses, and studies results became more coherent when the significant interaction was used. Conclusion The p-value of the interaction between main variables must be analyzed with caution because it can change the outcomes of research studies. Researchers are strongly advised to interpret carefully the results of their statistical analysis in order to discuss the findings of their experiments properly. PMID:20857003

In Silico Identification of Proteins Associated with Drug-induced Liver Injury Based on the Prediction of Drug-target Interactions.

PubMed

Ivanov, Sergey; Semin, Maxim; Lagunin, Alexey; Filimonov, Dmitry; Poroikov, Vladimir

2017-07-01

Drug-induced liver injury (DILI) is the leading cause of acute liver failure as well as one of the major reasons for drug withdrawal from clinical trials and the market. Elucidation of molecular interactions associated with DILI may help to detect potentially hazardous pharmacological agents at the early stages of drug development. The purpose of our study is to investigate which interactions with specific human protein targets may cause DILI. Prediction of interactions with 1534 human proteins was performed for the dataset with information about 699 drugs, which were divided into three categories of DILI: severe (178 drugs), moderate (310 drugs) and without DILI (211 drugs). Based on the comparison of drug-target interactions predicted for different drugs' categories and interpretation of those results using clustering, Gene Ontology, pathway and gene expression analysis, we identified 61 protein targets associated with DILI. Most of the revealed proteins were linked with hepatocytes' death caused by disruption of vital cellular processes, as well as the emergence of inflammation in the liver. It was found that interaction of a drug with the identified targets is the essential molecular mechanism of the severe DILI for the most of the considered pharmaceuticals. Thus, pharmaceutical agents interacting with many of the identified targets may be considered as candidates for filtering out at the early stages of drug research. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interacting with target tracking algorithms in a gaze-enhanced motion video analysis system

NASA Astrophysics Data System (ADS)

Hild, Jutta; Krüger, Wolfgang; Heinze, Norbert; Peinsipp-Byma, Elisabeth; Beyerer, Jürgen

2016-05-01

Motion video analysis is a challenging task, particularly if real-time analysis is required. It is therefore an important issue how to provide suitable assistance for the human operator. Given that the use of customized video analysis systems is more and more established, one supporting measure is to provide system functions which perform subtasks of the analysis. Recent progress in the development of automated image exploitation algorithms allow, e.g., real-time moving target tracking. Another supporting measure is to provide a user interface which strives to reduce the perceptual, cognitive and motor load of the human operator for example by incorporating the operator's visual focus of attention. A gaze-enhanced user interface is able to help here. This work extends prior work on automated target recognition, segmentation, and tracking algorithms as well as about the benefits of a gaze-enhanced user interface for interaction with moving targets. We also propose a prototypical system design aiming to combine both the qualities of the human observer's perception and the automated algorithms in order to improve the overall performance of a real-time video analysis system. In this contribution, we address two novel issues analyzing gaze-based interaction with target tracking algorithms. The first issue extends the gaze-based triggering of a target tracking process, e.g., investigating how to best relaunch in the case of track loss. The second issue addresses the initialization of tracking algorithms without motion segmentation where the operator has to provide the system with the object's image region in order to start the tracking algorithm.

Target material dependence of positron generation from high intensity laser-matter interactions

DOE PAGES

Williams, G. J.; Barnak, D.; Fiksel, G.; ...

2016-12-06

Here, the effective scaling of positron-electron pair production by direct, ultraintense laser-matter interaction is investigated for a range of target materials and thicknesses. An axial magnetic field, acting as a focusing lens, was employed to measure positron signals for targets with atomic numbers as low as copper (Z – 29). The pair production yield was found to be consistent with the Bethe-Heitler mechanism, where the number of positrons emitted into a 1 steradian cone angle from the target rear was found to be proportional to Z 2. The unexpectedly low scaling results from Coulomb collisions that act to stop ormore » scatter positrons into high angles. Monte Carlo simulations support the experimental results, providing a comprehensive power-law scaling relationship for all elemental materials and densities.« less

Ejecta velocity distribution for impact cratering experiments on porous and low strength targets

NASA Astrophysics Data System (ADS)

Michikami, Tatsuhiro; Moriguchi, Kouichi; Hasegawa, Sunao; Fujiwara, Akira

2007-01-01

Impact cratering experiments on porous targets with various compressive strength ranging from ˜0.5 to ˜250 MPa were carried out in order to investigate the relationship between the ejecta velocity, and material strength or porosity of the target. A spherical alumina projectile (diameter ˜1 mm) was shot perpendicularly into the target surface with velocity ranging from 1.2 to 4.5 km/s (nominal 4 km/s), using a two-stage light-gas gun. The ejecta velocity was estimated from the fall point distance of ejecta. The results show that there are in fact a large fraction of ejecta with very low velocities when the material strength of the target is small and the porosity is high. As an example, in the case of one specific target (compressive strength ˜0.5 MPa and porosity 43%), the amount of ejecta with velocities lower than 1 m/s is about 40% of the total mass. The average velocity of the ejecta decreases with decreasing material strength or increasing the porosity of the target. Moreover, in our experiments, the ejecta velocity distributions normalized to total ejecta mass seem to be mainly dependent on the material strength of the target, and not so greatly on the porosity. We also compare our experimental results with those of Gault et al. [1963. Spray ejected from the lunar surface by meteoroid impact. NASA Technical Note D-1767] and Housen [1992. Crater ejecta velocities for impacts on rocky bodies. LPSC XXIII, 555-556] for the ejecta velocity distribution using Housen's nondimensional scaling parameter. The ejecta velocity distributions of our experiments are lower than those of Gault et al. [1963. Spray ejected from the lunar surface by meteoroid impact. NASA Technical Note D-1767] and Housen [1992. Crater ejecta velocities for impacts on rocky bodies. LPSC XIII, 555-556].

‘Partial’ competition of heterobivalent ligand binding may be mistaken for allosteric interactions: a comparison of different target interaction models

PubMed Central

Vauquelin, Georges; Hall, David; Charlton, Steven J

2015-01-01

Background and Purpose Non-competitive drugs that confer allosteric modulation of orthosteric ligand binding are of increasing interest as therapeutic agents. Sought-after advantages include a ceiling level to drug effect and greater receptor-subtype selectivity. It is thus important to determine the mode of interaction of newly identified receptor ligands early in the drug discovery process and binding studies with labelled orthosteric ligands constitute a traditional approach for this. According to the general allosteric ternary complex model, allosteric ligands that exhibit negative cooperativity may generate distinctive ‘competition’ curves: they will not reach baseline levels and their nadir will increase in par with the orthosteric ligand concentration. This behaviour is often considered a key hallmark of allosteric interactions. Experimental Approach The present study is based on differential equation-based simulations. Key Results The differential equation-based simulations revealed that the same ‘competition binding’ pattern was also obtained when a monovalent ligand binds to one of the target sites of a heterobivalent ligand, even if this process is exempt of allosteric interactions. This pattern was not strictly reciprocal when the binding of each of the ligands was recorded. The prominence of this phenomenon may vary from one heterobivalent ligand to another and we suggest that this phenomenon may take place with ligands that have been proposed to bind according to ‘two-domain’ and ‘charnière’ models. Conclusions and Implications The present findings indicate a familiar experimental situation where bivalency may give rise to observations that could inadvertently be interpreted as allosteric binding. Yet, both mechanisms could be differentiated based on alternative experiments and structural considerations. PMID:25537684

Recommendation Techniques for Drug-Target Interaction Prediction and Drug Repositioning.

PubMed

Alaimo, Salvatore; Giugno, Rosalba; Pulvirenti, Alfredo

2016-01-01

The usage of computational methods in drug discovery is a common practice. More recently, by exploiting the wealth of biological knowledge bases, a novel approach called drug repositioning has raised. Several computational methods are available, and these try to make a high-level integration of all the knowledge in order to discover unknown mechanisms. In this chapter, we review drug-target interaction prediction methods based on a recommendation system. We also give some extensions which go beyond the bipartite network case.

Measuring the Density of Liquid Targets in the SeaQuest Experiment

NASA Astrophysics Data System (ADS)

Xi, Zhaojia; SeaQuest/E906 Collaboration

2015-10-01

The SeaQuest (E906) experiment, using the 120 GeV proton beam from the Main Injector at the Fermi National Accelerator Lab (FNAL), is studying the quark and antiquark structure of the nucleon using the Drell-Yan process. Based on the cross section ratios, σ (p + d) / σ (p + p) , SeaQuest will extract the Bjorken-x dependnce of the d / u ratio. The measurement will cover the large region (x > 0 . 25) with improved accuracy compared to the previous E866/Nusea experiment. Liquid D2 (LD2) and Liquid H2 (LH2) are the targets used in the SeaQuest experiment. The densities of LD2 and LH2 targets are two important quantities for the determination of the d / u ratio. We measure the pressure and temperature inside the flasks, from which the densities are calculated. The method, measurements and results of this study will be presented. This work is supported by U.S. DOE MENP Grant DE-FG02-03ER41243.

Scaling law deduced from impact-cratering experiments on basalt targets

NASA Astrophysics Data System (ADS)

Takagi, Y.; Hasegawa, S.; Suzuki, A.

2014-07-01

Since impact-cratering phenomena on planetary bodies were the key process which modified the surface topography and formed regolith layers, many experiments on non-cohesive materials (sand, glass beads) were performed. On the other hand, experiments on natural rocks were limited. Especially, experiments on basalt targets are rare, although basalt is the most common rocky material on planetary surfaces. The reason may be the difficulties of obtaining basalt samples suitable for cratering experiments. Recently, we obtained homogenous and crackless large basalt blocks. We performed systematic cratering experiments using the basalt targets. Experimental Procedure: Impact experiments were performed using a double stage light-gas (hydrogen) gun on the JAXA Sagamihara campus. Spherical projectiles of nylon, aluminum, stainless steel, and tungsten carbide were launched at velocities between 2400 and 6100 m/sec. The projectiles were 1.0 to 7.1 mm in diameter and 0.004 to 0.22 g in mass. The incidence angle was fixed at 90 degrees. The targets were rectangular blocks of Ukrainian basalt. The impact plane was a square with 20-cm sides. The thickness was 9 cm. Samples were cut out from a columnar block so that the impact plane might become perpendicular to the axis of the columnar joint. The mass was about 10.5 kg. The density was 2920 ± 10 kg/m^3 . Twenty eight shots were performed. Three-dimensional shapes of craters were measured by an X-Y stage with a laser displacement sensor (Keyence LK-H150). The interval between the measurement points was 200 micrometer. The volume, depth, and aperture area of the crater were calculated from the 3-D data using analytical software. Since the shapes of the formed craters are markedly asymmetrical, the diameter of the circle whose area is equal to the aperture area was taken as the crater diameter. Results: The diameter, depth, and the volume of the formed craters are normalized by the π parameters. Experimental conditions are also

Colloidal Disorder-Order Transition Experiment Probes Particle Interactions in Microgravity

NASA Technical Reports Server (NTRS)

1997-01-01

Everything in the universe is made up of the same basic building blocks - atoms. All physical properties of matter such as weight, hardness, and color are determined by the kind of atoms present and the way they interact with each other. The Colloidal Disorder-Order Transition (CDOT) shuttle flight experiment tested fundamental theories that model atomic interactions. The experiment was part of the Second United States Microgravity Laboratory (USML-2) aboard the Space Shuttle Columbia, which flew from October 20 to November 5, 1995.

Target Fabrication Technology and New Functional Materials for Laser Fusion and Laser-Plasma Experiment

NASA Astrophysics Data System (ADS)

Nagai, Keiji; Norimatsu, Takayoshi; Izawa, Yasukazu

Target fabrication technique is a key issue of laser fusion. We present a comprehensive, up-to-data compilation of laser fusion target fabrication and relating new materials. To achieve highly efficient laser implosion, organic and inorganic highly spherical millimeter-sized capsules and cryogenic hydrogen layers inside should be uniform in diameter and thickness within sub-micrometer ˜ nanometer error. Porous structured targets and molecular cluster targets are required for laser-plasma experiments and applications. Various technologies and new materials concerning above purposes are summarized including fast-ignition targets, equation-of-state measurement targets, high energy ion generation targets, etc.

Comparison of hydrodynamic simulations with two-shockwave drive target experiments

NASA Astrophysics Data System (ADS)

Karkhanis, Varad; Ramaprabhu, Praveen; Buttler, William

2015-11-01

We consider hydrodynamic continuum simulations to mimic ejecta generation in two-shockwave target experiments, where metallic surface is loaded by two successive shock waves. Time of second shock in simulations is determined to match experimental amplitudes at the arrival of the second shock. The negative Atwood number A --> - 1 of ejecta simulations leads to two successive phase inversions of the interface corresponding to the passage of the shocks from heavy to light media in each instance. Metallic phase of ejecta (solid/liquid) depends on shock loading pressure in the experiment, and we find that hydrodynamic simulations quantify the liquid phase ejecta physics with a fair degree of accuracy, where RM instability is not suppressed by the strength effect. In particular, we find that our results of free surface velocity, maximum ejecta velocity, and maximum ejecta areal density are in excellent agreement with their experimental counterparts, as well as ejecta models. We also comment on the parametric space for hydrodynamic simulations in which they can be used to compare with the target experiments. This work was supported in part by the (U.S.) Department of Energy (DOE) under Contract No. DE-AC52-06NA2-5396.

Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets.

PubMed

Mohan, Nimmy; Sudheesh, A P; Francis, Nimmy; Anderson, Richard; Laishram, Rakesh S

2015-08-18

Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3'-end processing. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Effect of target composition on proton acceleration in ultraintense laser-thin foil interaction

NASA Astrophysics Data System (ADS)

Liu, Qingcao; Liu, Meng; Yu, Tongpu; Ding, Pengji; Liu, Zuoye; Sun, Shaohua; Liu, Xiaoliang; Lu, Xing; Guo, Zeqin; Hu, Bitao

2012-09-01

The interactions of ultraintense circularly polarized laser pulses with a mixed solid target and a double-layer target are studied by two-dimensional particle-in-cell simulations. Different carbon and proton compositions in the targets are used in the simulations. It is shown that the proton acceleration mechanisms in both targets are very sensitive to the ion density ratios between protons and carbon ions. For a mixed solid target, a relatively low proton density gives rise to monoenergetic peaks in the proton energy spectrum while a high proton density leads to a large cut-off energy and wide energy spread. With the increase of the ratio, the so-called directed-Coulomb-explosion becomes dominated over the radiation pressure. Surprisingly, for a double-layer target with a front proton layer and an ultrathin rear carbon layer, a highly monoenergetic proton beam with a peak energy of 1.7 GeV/u, an energy spread of ˜4%, and a divergency angle of 2° can be obtained, which might have diverse applications in medical therepy and proton imaging in future.

Mechanism of MicroRNA-Target Interaction: Molecular Dynamics Simulations and Thermodynamics Analysis

PubMed Central

Wang, Yonghua; Li, Yan; Ma, Zhi; Yang, Wei; Ai, Chunzhi

2010-01-01

MicroRNAs (miRNAs) are endogenously produced ∼21-nt riboregulators that associate with Argonaute (Ago) proteins to direct mRNA cleavage or repress the translation of complementary RNAs. Capturing the molecular mechanisms of miRNA interacting with its target will not only reinforce the understanding of underlying RNA interference but also fuel the design of more effective small-interfering RNA strands. To address this, in the present work the RNA-bound (Ago-miRNA, Ago-miRNA-target) and RNA-free Ago forms were analyzed by performing both molecular dynamics simulations and thermodynamic analysis. Based on the principal component analysis results of the simulation trajectories as well as the correlation analysis in fluctuations of residues, we discover that: 1) three important (PAZ, Mid and PIWI) domains exist in Argonaute which define the global dynamics of the protein; 2) the interdomain correlated movements are so crucial for the interaction of Ago-RNAs that they not only facilitate the relaxation of the interactions between residues surrounding the RNA binding channel but also induce certain conformational changes; and 3) it is just these conformational changes that expand the cavity of the active site and open putative pathways for both the substrate uptake and product release. In addition, by thermodynamic analysis we also discover that for both the guide RNA 5′-end recognition and the facilitated site-specific cleavage of the target, the presence of two metal ions (of Mg2+) plays a predominant role, and this conclusion is consistent with the observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA-mRNA). Our results find that it is the set of arginine amino acids concentrated in the nucleotide-binding channel in Ago, instead of the conventionally-deemed seed base-paring, that makes greater contributions in stabilizing the binding of the nucleic acids to Ago. PMID:20686687

Hydrodynamic interactions for complex-shaped nanocarriers in targeted drug delivery

NASA Astrophysics Data System (ADS)

Wang, Yaohong; Eckmann, David; Radhakrishnan, Ravi; Ayyaswamy, Portonovo

2014-11-01

Nanocarrier motion in a blood vessel involves hydrodynamic and Brownian interactions, which collectively dictate the efficacy in targeted drug delivery. The shape of nanocarriers plays a crucial role in drug delivery. In order to quantify the flow and association properties of elliptical nanoparticles, we have developed an arbitrary Lagrangian-Eulerian framework with capabilities to simulate the hydrodynamic motion of nanoparticles of arbitrary shapes. We introduce the quaternions for rotational motion, and two collision models, namely, (a) an impulse-based model for wall-particle collision, and (b) the short-range repulsive Gay-Berne potential for particle-particle collision. We also study the red blood cell and nanocarrier (such as ellipsoid) interactions. We compare our results with those obtained for a hard sphere model for both RBCs and nanocarriers. Supported by NIH through grant U01-EB016027.

Extracting sets of chemical substructures and protein domains governing drug-target interactions.

PubMed

Yamanishi, Yoshihiro; Pauwels, Edouard; Saigo, Hiroto; Stoven, Véronique

2011-05-23

The identification of rules governing molecular recognition between drug chemical substructures and protein functional sites is a challenging issue at many stages of the drug development process. In this paper we develop a novel method to extract sets of drug chemical substructures and protein domains that govern drug-target interactions on a genome-wide scale. This is made possible using sparse canonical correspondence analysis (SCCA) for analyzing drug substructure profiles and protein domain profiles simultaneously. The method does not depend on the availability of protein 3D structures. From a data set of known drug-target interactions including enzymes, ion channels, G protein-coupled receptors, and nuclear receptors, we extract a set of chemical substructures shared by drugs able to bind to a set of protein domains. These two sets of extracted chemical substructures and protein domains form components that can be further exploited in a drug discovery process. This approach successfully clusters protein domains that may be evolutionary unrelated but that bind a common set of chemical substructures. As shown in several examples, it can also be very helpful for predicting new protein-ligand interactions and addressing the problem of ligand specificity. The proposed method constitutes a contribution to the recent field of chemogenomics that aims to connect the chemical space with the biological space.

Genome scale enzyme–metabolite and drug–target interaction predictions using the signature molecular descriptor

DOE PAGES

Faulon, Jean-Loup; Misra, Milind; Martin, Shawn; ...

2007-11-23

Motivation: Identifying protein enzymatic or pharmacological activities are important areas of research in biology and chemistry. Biological and chemical databases are increasingly being populated with linkages between protein sequences and chemical structures. Additionally, there is now sufficient information to apply machine-learning techniques to predict interactions between chemicals and proteins at a genome scale. Current machine-learning techniques use as input either protein sequences and structures or chemical information. We propose here a method to infer protein–chemical interactions using heterogeneous input consisting of both protein sequence and chemical information. Results: Our method relies on expressing proteins and chemicals with a common cheminformaticsmore » representation. We demonstrate our approach by predicting whether proteins can catalyze reactions not present in training sets. We also predict whether a given drug can bind a target, in the absence of prior binding information for that drug and target. Lastly, such predictions cannot be made with current machine-learning techniques requiring binding information for individual reactions or individual targets.« less

HDice, Highly-Polarized Low-Background Frozen-Spin HD Targets for CLAS experiments at Jefferson Lab

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

Wei, Xiangdong; Bass, Christopher; D'Angelo, Annalisa

2012-12-01

Large, portable frozen-spin HD (Deuterium-Hydride) targets have been developed for studying nucleon spin properties with low backgrounds. Protons and Deuterons in HD are polarized at low temperatures (~10mK) inside a vertical dilution refrigerator (Oxford Kelvinox-1000) containing a high magnetic field (up to 17T). The targets reach a frozen-spin state within a few months, after which they can be cold transferred to an In-Beam Cryostat (IBC). The IBC, a thin-walled dilution refrigerator operating either horizontally or vertically, is use with quasi-4{pi} detector systems in open geometries with minimal energy loss for exiting reaction products in nucleon structure experiments. The first applicationmore » of this advanced target system has been used for Spin Sum Rule experiments at the LEGS facility in Brookhaven National Laboratory. An improved target production and handling system has been developed at Jefferson Lab for experiments with the CEBAF Large Acceptance Spectrometer, CLAS.« less

Experiments in interactive panoramic cinema

NASA Astrophysics Data System (ADS)

Fisher, Scott S.; Anderson, Steve; Ruiz, Susana; Naimark, Michael; Hoberman, Perry; Bolas, Mark; Weinberg, Richard

2005-03-01

For most of the past 100 years, cinema has been the premier medium for defining and expressing relations to the visible world. However, cinematic spectacles delivered in darkened theaters are predicated on a denial of both the body and the physical surroundings of the spectators who are watching it. To overcome these deficiencies, filmmakers have historically turned to narrative, seducing audiences with compelling stories and providing realistic characters with whom to identify. This paper describes several research projects in interactive panoramic cinema that attempt to sidestep the narrative preoccupations of conventional cinema and instead are based on notions of space, movement and embodied spectatorship rather than traditional storytelling. Example projects include interactive works developed with the use of a unique 360 degree camera and editing system, and also development of panoramic imagery for a large projection environment with 14 screens on 3 adjacent walls in a 5-4-5 configuration with observations and findings from an experiment projecting panoramic video on 12 of the 14, in a 4-4-4 270 degree configuration.

Cell-to-cell interactions in changed gravity: Ground-based and flight experiments

NASA Astrophysics Data System (ADS)

Buravkova, L.; Romanov, Yu.; Rykova, M.; Grigorieva, O.; Merzlikina, N.

2005-07-01

Cell-to-cell interactions play an important role in all physiological processes and are mediated by humoral and mechanical factors. Mechanosensitive cells (e.g., osteocytes, chondrocytes, and fibroblasts) can be studied ex vivo to understand the effects of an altered gravity environment. In particular, cultured endothelial cells (EC) are very sensitive to a broad spectrum of mechanical and biochemical stimuli. Earlier, we demonstrated that clinorotation leads to cytoskeletal remodeling in cultured ECs. Long-term gravity vector changes also modulate the expression of surface adhesion molecules (ICAM-1, E-selectin, VCAM-1) on cultured ECs. To study the interactions of geterological cells, we cocultured endothelial monolayers and human lymphocytes, immune cells and myeloleucemic (K-560) cells. It was found that, although clinorotation did not alter the basal adhesion level of non-activated immune cells on endothelial monolayers, the adhesion of PMA-activated lymphocytes was increased. During flight experiments onboard the Russian segment of the International Space Station, we measured the cytotoxic activity of natural killer (NK) cells incubated with labeled target cells. It was found that immune cells in microgravity retained their ability to contact, recognize, and destroy oncogenic cells in vitro. Together, our data concerning the effects of simulated and real microgravity suggest that, despite changes in the cytoskeleton, cell motility, and expression of adhesion molecules, cell-cell interactions are not compromised, thus preserving the critical physiological functions of immune and endothelial cells.

SPQR II: A beam-plasma interaction experiment

NASA Astrophysics Data System (ADS)

Bimbot, R.; Della-Negra, S.; Gardès, D.; Rivet, M. F.; Fleurier, C.; Dumax, B.; Hoffman, D. H. H.; Weyrich, K.; Deutsch, C.; Maynard, G.

1986-01-01

SPQR II is an interaction experiment designed to probe energy -and charge-exchange of Cn+ ions at 2 MeV/a.m.u., flowing through a fully ionized plasma column of hydrogen with nℓ=1019 e-cm-2 at T=5 eV. One expects a factor of two enhanced stopping over the cold gas case.

Evaluating the ISDN line to deliver interactive multimedia experiences

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

Michaels, D.K.

1994-05-06

We will use the 128 kilobit/sec ISDN connection from the Lawrence Livermore National Laboratory to the Livermore High School Math Learning Center to provide students there with interactive multimedia educational experiences. These experiences may consist of tutorials, exercises, and interactive puzzles to teach students` course material. We will determine if it is possible to store the multimedia files at LLNL and deliver them to the student machines via FTP as they are needed. An evaluation of the effect of the ISDN data rate is a substantial component of our research and suggestions on how to best use the ISDN linemore » in this capacity will be given.« less

Illusions of integration are subjectively impenetrable: Phenomenological experience of Lag 1 percepts during dual-target RSVP.

PubMed

Simione, Luca; Akyürek, Elkan G; Vastola, Valentina; Raffone, Antonino; Bowman, Howard

2017-05-01

We investigated the relationship between different kinds of target reports in a rapid serial visual presentation task, and their associated perceptual experience. Participants reported the identity of two targets embedded in a stream of stimuli and their associated subjective visibility. In our task, target stimuli could be combined together to form more complex ones, thus allowing participants to report temporally integrated percepts. We found that integrated percepts were associated with high subjective visibility scores, whereas reports in which the order of targets was reversed led to a poorer perceptual experience. We also found a reciprocal relationship between the chance of the second target not being reported correctly and the perceptual experience associated with the first one. Principally, our results indicate that integrated percepts are experienced as a unique, clear perceptual event, whereas order reversals are experienced as confused, similar to cases in which an entirely wrong response was given. Copyright © 2017 Elsevier Inc. All rights reserved.

The DOSY experiment provides insights into the protegrin-lipid interaction

NASA Astrophysics Data System (ADS)

Malliavin, T. E.; Louis, V.; Delsuc, M. A.

1998-02-01

The measure of translational diffusion using PFG NMR has known a renewal of interest with the development of the DOSY experiments. The extraction of diffusion coefficients from these experiments requires an inverse Laplace transform. We present here the use of the Maximum Entropy technique to perform this transform, and an application of this method to investigate the interaction protegrin-lipid. We show that the analysis by DOSY experiments permits to determine some of the interaction features. La mesure de diffusion translationnelle par gradients de champs pulsés en RMN a connu un regain d'intérêt avec le développement des expériences de DOSY. L'extraction de coefficients de diffusion à partir de ces expériences nécessite l'application d'une transformée de Laplace inverse. Nous présentons ici l'utilisation de la méthode d'Entropie Maximum pour effectuer cette transformée, ainsi qu'une application de l'expérience de DOSY pour étudier une interaction protégrine-lipide. Nous montrons que l'analyse par l'expérience de DOSY permet de déterminer certaines des caractéristiques de cette interaction.

INSPIRE - Premission. [Interactive NASA Space Physics Ionosphere Radio Experiment

NASA Technical Reports Server (NTRS)

Taylor, William W. L.; Mideke, Michael; Pine, William E.; Ericson, James D.

1992-01-01

The Interactive NASA Space Physics Ionosphere Radio Experiment (INSPIRE) designed to assist in a Space Experiments with Particle Accelerators (SEPAC) project is discussed. INSPIRE is aimed at recording data from a large number of receivers on the ground to determine the exact propagation paths and absorption of radio waves at frequencies between 50 Hz and 7 kHz. It is indicated how to participate in the experiment that will involve high school classes, colleges, and amateur radio operators.

Solar array module plasma interactions experiment (SAMPIE) - Science and technology objectives

NASA Technical Reports Server (NTRS)

Hillard, G. B.; Ferguson, Dale C.

1993-01-01

The solar array module plasma interactions experiment (SAMPIE) is an approved NASA flight experiment manifested for Shuttle deployment in early 1994. The SAMPIE experiment is designed to investigate the interaction of high voltage space power systems with ionospheric plasma. To study the behavior of solar cells, a number of solar cell coupons (representing design technologies of current interest) will be biased to high voltages to measure both arcing and current collection. Various theories of arc suppression will be tested by including several specially modified cell coupons. Finally, SAMPIE will include experiments to study the basic nature of arcing and current collection. This paper describes the rationale for a space flight experiment, the measurements to be made, and the significance of the expected results. A future paper will present a detailed discussion of the engineering design.

Validating An Analytic Completeness Model for Kepler Target Stars Based on Flux-level Transit Injection Experiments

NASA Astrophysics Data System (ADS)

Catanzarite, Joseph; Burke, Christopher J.; Li, Jie; Seader, Shawn; Haas, Michael R.; Batalha, Natalie; Henze, Christopher; Christiansen, Jessie; Kepler Project, NASA Advanced Supercomputing Division

2016-06-01

The Kepler Mission is developing an Analytic Completeness Model (ACM) to estimate detection completeness contours as a function of exoplanet radius and period for each target star. Accurate completeness contours are necessary for robust estimation of exoplanet occurrence rates.The main components of the ACM for a target star are: detection efficiency as a function of SNR, the window function (WF) and the one-sigma depth function (OSDF). (Ref. Burke et al. 2015). The WF captures the falloff in transit detection probability at long periods that is determined by the observation window (the duration over which the target star has been observed). The OSDF is the transit depth (in parts per million) that yields SNR of unity for the full transit train. It is a function of period, and accounts for the time-varying properties of the noise and for missing or deweighted data.We are performing flux-level transit injection (FLTI) experiments on selected Kepler target stars with the goal of refining and validating the ACM. “Flux-level” injection machinery inserts exoplanet transit signatures directly into the flux time series, as opposed to “pixel-level” injection, which inserts transit signatures into the individual pixels using the pixel response function. See Jie Li's poster: ID #2493668, "Flux-level transit injection experiments with the NASA Pleiades Supercomputer" for details, including performance statistics.Since FLTI is affordable for only a small subset of the Kepler targets, the ACM is designed to apply to most Kepler target stars. We validate this model using “deep” FLTI experiments, with ~500,000 injection realizations on each of a small number of targets and “shallow” FLTI experiments with ~2000 injection realizations on each of many targets. From the results of these experiments, we identify anomalous targets, model their behavior and refine the ACM accordingly.In this presentation, we discuss progress in validating and refining the ACM, and we

Observation of anisotropic interactions between metastable atoms and target molecules by two-dimensional collisional ionization electron spectroscopy

NASA Astrophysics Data System (ADS)

Kishimoto, Naoki; Ohno, Koichi

Excited metastable atoms colliding with target molecules can sensitively probe outer properties of molecules by chemi-ionization (Penning ionization) from molecular orbitals in the outer region, since metastable atoms cannot penetrate into the repulsive interaction wall around the molecules. By means of two-dimensional measurements using kinetic energy analysis of electrons combined with a velocity-resolved metastable beam, one can obtain information on the anisotropic interaction between the colliding particles without any control of orientation or alignment of target molecules. We have developed a classical trajectory method to calculate the collision energy dependence of partial ionization cross-sections (CEDPICS) on the anisotropic interaction potential energy surface, which has enabled us to study stereodynamics between metastable atoms and target molecules as well as the spatial distribution of molecular orbitals and electron ejection functions which have a relation with entrance and exit channels of the reaction. Based on the individual CEDPICS, the electronic structure of molecules can also be elucidated.

Centrifuge impact cratering experiments: Scaling laws for non-porous targets

NASA Technical Reports Server (NTRS)

Schmidt, Robert M.

1987-01-01

This research is a continuation of an ongoing program whose objective is to perform experiments and to develop scaling relationships for large body impacts onto planetary surfaces. The development of the centrifuge technique has been pioneered by the present investigator and is used to provide experimental data for actual target materials of interest. With both powder and gas guns mounted on a rotor arm, it is possible to match various dimensionless similarity parameters, which have been shown to govern the behavior of large scale impacts. Current work is directed toward the determination of scaling estimates for nonporous targets. The results are presented in summary form.

VLF wave-wave interaction experiments in the magnetosphere

NASA Technical Reports Server (NTRS)

Chang, D. C. D.

1978-01-01

VLF wave-wave interaction experiments were carried out by injecting various forms of VLF pulses into the magnetosphere from a 21.2 km dipole antenna at Siple, Antarctica. The injected signals propagate along a geomagnetic field line and often interact strongly with energetic electrons trapped in the radiation belts near the equator. Signals may be amplified and trigger emissions. These signals may then interact with one another through these energetic electrons. This report is divided into three parts. In the first part, simulations of VLF pulses propagating in the magnetosphere are carried out. In the second part, it is found for the first time that a 10 ms gap in a triggering wave can induce emission, which may then interact with the post-gap signals. In the third part, sideband triggering is reported for the first time.

Synaptic activity induces input-specific rearrangements in a targeted synaptic protein interaction network.

PubMed

Lautz, Jonathan D; Brown, Emily A; VanSchoiack, Alison A Williams; Smith, Stephen E P

2018-05-27

Cells utilize dynamic, network level rearrangements in highly interconnected protein interaction networks to transmit and integrate information from distinct signaling inputs. Despite the importance of protein interaction network dynamics, the organizational logic underlying information flow through these networks is not well understood. Previously, we developed the quantitative multiplex co-immunoprecipitation platform, which allows for the simultaneous and quantitative measurement of the amount of co-association between large numbers of proteins in shared complexes. Here, we adapt quantitative multiplex co-immunoprecipitation to define the activity dependent dynamics of an 18-member protein interaction network in order to better understand the underlying principles governing glutamatergic signal transduction. We first establish that immunoprecipitation detected by flow cytometry can detect activity dependent changes in two known protein-protein interactions (Homer1-mGluR5 and PSD-95-SynGAP). We next demonstrate that neuronal stimulation elicits a coordinated change in our targeted protein interaction network, characterized by the initial dissociation of Homer1 and SynGAP-containing complexes followed by increased associations among glutamate receptors and PSD-95. Finally, we show that stimulation of distinct glutamate receptor types results in different modular sets of protein interaction network rearrangements, and that cells activate both modules in order to integrate complex inputs. This analysis demonstrates that cells respond to distinct types of glutamatergic input by modulating different combinations of protein co-associations among a targeted network of proteins. Our data support a model of synaptic plasticity in which synaptic stimulation elicits dissociation of preexisting multiprotein complexes, opening binding slots in scaffold proteins and allowing for the recruitment of additional glutamatergic receptors. This article is protected by copyright. All

Strategic targeting of essential host-pathogen interactions in chlamydial disease.

PubMed

Coombes, B K; Johnson, D L; Mahony, J B

2002-09-01

The chlamydiae are obligate intracellular gram-negative bacteria that are exquisitely adapted for exploitation of their hosts and contribute to a wide range of acute and chronic human diseases. Acute infections treated with non-cidal antibiotics can lead to the development of persistent, non-replicating bacteria with the corollary that these persistent (yet viable) chlamydiae can resist eradication by further antimicrobial treatment and cause chronic disease. These findings highlight an urgent need for therapeutics that are effective against persistent infections and call for creative approaches to identify potential drug targets. The C. pneumoniae and C. trachomatis genome projects have greatly expanded our knowledge of chlamydial pathogenesis and have provided an enormous potential for the identification and characterization of unknown genes and potential virulence factors in these bacteria. As intracellular pathogens, chlamydiae rely on host cells for all aspects of their survival, from the initial attachment with host cell membranes, to cellular invasion, acquisition of host cell metabolites and intracellular replication. As such, the molecules participating in interactions with the host could be attractive targets for therapeutic intervention. This review describes recent advances in chlamydial genomics, proteomics and cell biology that have cast light on host-pathogen relations that are essential for chlamydial survival. Using this knowledge, we discuss how strategically interfering with essential interactions between chlamydiae and the host cell could be exploited to develop an innovative, and potentially more relevant arsenal of therapeutic compounds.

Synthesis of mouse centromere-targeted polyamides and physico-chemical studies of their interaction with the target double-stranded DNA.

PubMed

Nozeret, Karine; Bonan, Marc; Yarmoluk, Serguiy M; Novopashina, Darya S; Boutorine, Alexandre S

2015-09-01

Synthetic minor groove-binding pyrrole-imidazole polyamides labeled by fluorophores are promising candidates for fluorescence imaging of double-stranded DNA in isolated chromosomes or fixed and living cells. We synthesized nine hairpin and two head-to-head tandem polyamides targeting repeated sequences from mouse major satellites. Their interaction with synthetic target dsDNA has been studied by physico-chemical methods in vitro before and after coupling to various fluorophores. Great variability in affinities and fluorescence properties reveals a conclusion that these properties do not only rely on recognition rules, but also on other known and unknown structural factors. Individual testing of each probe is needed before cellular applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.

PubMed

Bojadzic, Damir; Buchwald, Peter

2018-05-30

Protein-protein interactions (PPIs) that are part of the costimulatory and coinhibitory (immune checkpoint) signaling are critical for adequate T cell response and are important therapeutic targets for immunomodulation. Biologics targeting them have already achieved considerable clinical success in the treatment of autoimmune diseases or transplant recipients (e.g., abatacept, belatacept, and belimumab) as well as cancer (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab). In view of such progress, there have been only relatively limited efforts toward developing small-molecule PPI inhibitors (SMPPIIs) targeting these cosignaling interactions, possibly because they, as all other PPIs, are difficult to target by small molecules and were not considered druggable. Nevertheless, substantial progress has been achieved during the last decade. SMPPIIs proving the feasibility of such approaches have been identified through various strategies for a number of cosignaling interactions including CD40-CD40L, OX40-OX40L, BAFFR-BAFF, CD80-CD28, and PD-1-PD-L1s. Here, after an overview of the general aspects and challenges of SMPPII-focused drug discovery, we review them briefly together with relevant structural, immune-signaling, physicochemical, and medicinal chemistry aspects. While so far only a few of these SMPPIIs have shown activity in animal models (DRI-C21045 for CD40-D40L, KR33426 for BAFFR-BAFF) or reached clinical development (RhuDex for CD80-CD28, CA-170 for PD-1-PD-L1), there is proof-of-principle evidence for the feasibility of such approaches in immunomodulation. They can result in products that are easier to develop/manufacture and are less likely to be immunogenic or encounter postmarket safety events than corresponding biologics, and, contrary to them, can even become orally bioavailable. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Allelic Interactions among Pto-MIR475b and Its Four Target Genes Potentially Affect Growth and Wood Properties in Populus

PubMed Central

Xiao, Liang; Quan, Mingyang; Du, Qingzhang; Chen, Jinhui; Xie, Jianbo; Zhang, Deqiang

2017-01-01

MicroRNAs (miRNAs) play crucial roles in plant growth and development, but few studies have illuminated the allelic interactions among miRNAs and their targets in perennial plants. Here, we combined analysis of expression patterns and single-nucleotide polymorphism (SNP)-based association studies to explore the interactions between Pto-MIR475b and its four target genes (Pto-PPR1, Pto-PPR2, Pto-PPR3, and Pto-PPR4) in 435 unrelated individuals of Populus tomentosa. Expression patterns showed a significant negative correlation (r = -0.447 to -0.411, P < 0.01) between Pto-MIR475b and its four targets in eight tissues of P. tomentosa, suggesting that Pto-miR475b may negatively regulate the four targets. Single SNP-based association studies identified 93 significant associations (P < 0.01, Q < 0.1) representing associations of 80 unique SNPs in Pto-MIR475b and its four targets with nine traits, revealing their potential roles in tree growth and wood formation. Moreover, one common SNP in the precursor region significantly altered the secondary structure of the pre-Pto-miR475b and changed the expression level of Pto-MIR475b. Analysis of epistatic interactions identified 115 significant SNP–SNP associations (P < 0.01) representing 45 unique SNPs from Pto-MIR475b and its four targets for 10 traits, revealing that genetic interactions between Pto-MIR475b and its targets influence quantitative traits of perennial plants. Our study provided a feasible strategy to study population genetics in forest trees and enhanced our understanding of miRNAs by dissecting the allelic interactions between this miRNA and its targets in P. tomentosa. PMID:28680433

RFDT: A Rotation Forest-based Predictor for Predicting Drug-Target Interactions Using Drug Structure and Protein Sequence Information.

PubMed

Wang, Lei; You, Zhu-Hong; Chen, Xing; Yan, Xin; Liu, Gang; Zhang, Wei

2018-01-01

Identification of interaction between drugs and target proteins plays an important role in discovering new drug candidates. However, through the experimental method to identify the drug-target interactions remain to be extremely time-consuming, expensive and challenging even nowadays. Therefore, it is urgent to develop new computational methods to predict potential drugtarget interactions (DTI). In this article, a novel computational model is developed for predicting potential drug-target interactions under the theory that each drug-target interaction pair can be represented by the structural properties from drugs and evolutionary information derived from proteins. Specifically, the protein sequences are encoded as Position-Specific Scoring Matrix (PSSM) descriptor which contains information of biological evolutionary and the drug molecules are encoded as fingerprint feature vector which represents the existence of certain functional groups or fragments. Four benchmark datasets involving enzymes, ion channels, GPCRs and nuclear receptors, are independently used for establishing predictive models with Rotation Forest (RF) model. The proposed method achieved the prediction accuracy of 91.3%, 89.1%, 84.1% and 71.1% for four datasets respectively. In order to make our method more persuasive, we compared our classifier with the state-of-theart Support Vector Machine (SVM) classifier. We also compared the proposed method with other excellent methods. Experimental results demonstrate that the proposed method is effective in the prediction of DTI, and can provide assistance for new drug research and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Target productions in forward and backward hemispheres in the interactions of 28Si-EM at 14.6A GeV

NASA Astrophysics Data System (ADS)

Abdelsalam, A.; El-Nagdy, M. S.; Abdalla, A. M.; Saber, A.

2015-11-01

This paper search for the results and properties of slow particle productions, appear as a gray and black tracks in nuclear emulsions, producing secondary charged particles which are emitted from 28Si interactions with emulsion nuclei at 14.6A GeV. The forward particles emission of interactions, (θlab<90∘) as well as the backward ones (θlab≥90∘), have been investigated. It includes the effect of both projectile mass number and energy on the production and multiplicities of these particles. The results compared with other experiments for the same target but with different projectiles and energies. The experimental data show that there are two different mechanisms responsible for the production of gray particles for the chosen channels of emission angles and each are energy dependence. This dependence is weakly on the projectile mass number. The same investigations are applied for black tracks producing particles. The experimental results show the production of these particles is purely target fragments independent on both projectile mass number and its energy. The anisotropy ratio of angular distribution (F/B) is applied for both kinds of particles which are found the value for gray particle production depends on the direction of emissions while it is unchanged for black particles.

Ultra-intense laser interaction with specially-designed targets as a source of energetic protons

NASA Astrophysics Data System (ADS)

Psikal, J.; Matys, M.

2017-05-01

In this contribution, we discuss the optimization of laser driven proton acceleration efficiency by nanostructured targets, interpret the experimental results showing the manipulation of proton beam profiles by nanosctructured rear surface of the targets and investigate the acceleration of protons from hydrogen solid ribbon by PW-class lasers, with the help of multidimensional particle-in-cell simulations. Microstructured hollow targets are proposed to enhance the absorption of the laser pulse energy while keeping the target thickness to minimum, which is both favorable for enhanced efficiency of the acceleration of protons. Thin targets with grating structures of various configurations on their rear sides stretch the proton beams in the perpendicular direction to the grating orientation due to transverse electric fields generated inside the target grooves and can reduce the proton beam divergence in the parallel direction to the grating due to a lower density of the stretched beam compared with flat foils. Finally, it is shown that when multiPW laser pulse interacts with hydrogen solid ribbon, hole boring radiation pressure acceleration (RPA) dominates over the target normal sheath acceleration (TNSA).

Specificity in the interaction of natural products with their target proteins--a biochemical and structural insight.

PubMed

Venkatraman, Prasanna

2010-06-01

Natural products are an abundant source of anti cancer agents. They act as cytotoxic drugs, and inhibitors of apoptosis, transcription, cell proliferation and angiogenesis. While pathways targeted by natural products have been well studied, there is paucity of information about the in vivo molecular target/s of these compounds. This review summarizes some of the natural compounds for which the molecular targets, mechanism of action and structural basis of specificity have been well documented. These examples illustrate that 'off target' binding can be explained on the basis of diversity inherent to biomolecular interactions. There is enough evidence to suggest that natural compounds are potent and versatile warheads that can be optimized for a multi targeted therapeutic intervention in cancer.

Targeting protein-protein interactions in hematologic malignancies: still a challenge or a great opportunity for future therapies?

PubMed Central

Cierpicki, Tomasz; Grembecka, Jolanta

2015-01-01

Summary Over the past several years, there has been an increasing research effort focused on inhibition of protein-protein interactions (PPIs) to develop novel therapeutic approaches for cancer, including hematologic malignancies. These efforts have led to development of small molecule inhibitors of PPIs, some of which already advanced to the stage of clinical trials while others are at different stages of pre-clinical optimization, emphasizing PPIs as an emerging and attractive class of drug targets. Here, we review several examples of recently developed inhibitors of protein-protein interactions highly relevant to hematologic cancers. We address the existing skepticism about feasibility of targeting PPIs and emphasize potential therapeutic benefit from blocking PPIs in hematologic malignancies. We then use these examples to discuss the approaches for successful identification of PPI inhibitors and provide analysis of the protein-protein interfaces, with the goal to address ‘druggability’ of new PPIs relevant to hematology. We discuss lessons learned to improve the success of targeting new protein-protein interactions and evaluate prospects and limits of the research in this field. We conclude that not all PPIs are equally tractable for blocking by small molecules, and detailed analysis of PPI interfaces is critical for selection of those with the highest chance of success. Together, our analysis uncovers patterns that should help to advance drug discovery in hematologic malignancies by successful targeting of new protein-protein interactions. PMID:25510283

Liquid Hydrogen Target Experience at SLAC

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

Weisend, J.G.; Boyce, R.; Candia, A.

2005-08-29

Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small ''beer can'' targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability. This paper surveys the evolutionmore » of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible.« less

Stacking interactions in PUF-RNA complexes

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

Yiling Koh, Yvonne; Wang, Yeming; Qiu, Chen

2012-07-02

Stacking interactions between amino acids and bases are common in RNA-protein interactions. Many proteins that regulate mRNAs interact with single-stranded RNA elements in the 3' UTR (3'-untranslated region) of their targets. PUF proteins are exemplary. Here we focus on complexes formed between a Caenorhabditis elegans PUF protein, FBF, and its cognate RNAs. Stacking interactions are particularly prominent and involve every RNA base in the recognition element. To assess the contribution of stacking interactions to formation of the RNA-protein complex, we combine in vivo selection experiments with site-directed mutagenesis, biochemistry, and structural analysis. Our results reveal that the identities of stackingmore » amino acids in FBF affect both the affinity and specificity of the RNA-protein interaction. Substitutions in amino acid side chains can restrict or broaden RNA specificity. We conclude that the identities of stacking residues are important in achieving the natural specificities of PUF proteins. Similarly, in PUF proteins engineered to bind new RNA sequences, the identity of stacking residues may contribute to 'target' versus 'off-target' interactions, and thus be an important consideration in the design of proteins with new specificities.« less

A systems biology perspective on plant-microbe interactions: biochemical and structural targets of pathogen effectors.

PubMed

Pritchard, Leighton; Birch, Paul

2011-04-01

Plants have biochemical defences against stresses from predators, parasites and pathogens. In this review we discuss the interaction of plant defences with microbial pathogens such as bacteria, fungi and oomycetes, and viruses. We examine principles of complex dynamic networks that allow identification of network components that are differentially and predictably sensitive to perturbation, thus making them likely effector targets. We relate these principles to recent developments in our understanding of known effector targets in plant-pathogen systems, and propose a systems-level framework for the interpretation and modelling of host-microbe interactions mediated by effectors. We describe this framework briefly, and conclude by discussing useful experimental approaches for populating this framework. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

New designs of LMJ targets for early ignition experiments

NASA Astrophysics Data System (ADS)

C-Clérouin, C.; Bonnefille, M.; Dattolo, E.; Fremerye, P.; Galmiche, D.; Gauthier, P.; Giorla, J.; Laffite, S.; Liberatore, S.; Loiseau, P.; Malinie, G.; Masse, L.; Poggi, F.; Seytor, P.

2008-05-01

The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 40 laser quads, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness are then designed for this purpose. A first strategy is to use scaled-down cylindrical hohlraums and capsules, taking advantage of our better understanding of the problem, set on theoretical modelling, simulations and experiments. Another strategy is to work specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, which is with parametric instabilities a crucial drawback of indirect drive. An alternative design is proposed, made up of the nominal 60 quads capsule, named A1040, in a rugby-shaped hohlraum. Robustness evaluations of these different targets are in progress.

How Do Interaction Experiences Influence Doctoral Students’ Academic Pursuits in Biomedical Research?

PubMed Central

Kong, Xiaoqing; Chakraverty, Devasmita; Jeffe, Donna B.; Andriole, Dorothy A.; Wathington, Heather D.; Tai, Robert H.

2014-01-01

This exploratory qualitative study investigated how doctoral students reported their personal and professional interaction experiences that they believed might facilitate or impede their academic pursuits in biomedical research. We collected 19 in-depth interviews with doctoral students in biomedical research from eight universities, and we based our qualitative analytic approach on the work of Miles and Huberman. The results indicated that among different sources and types of interaction, academic and emotional interactions from family and teachers in various stages essentially affected students’ persistence in the biomedical science field. In addition, co-mentorship among peers, departmental environment, and volunteer experiences were other essential factors. This study also found related experiences among women and underrepresented minority students that were important to their academic pursuit. PMID:26166928

How Do Interaction Experiences Influence Doctoral Students' Academic Pursuits in Biomedical Research?

PubMed

Kong, Xiaoqing; Chakraverty, Devasmita; Jeffe, Donna B; Andriole, Dorothy A; Wathington, Heather D; Tai, Robert H

2013-01-01

This exploratory qualitative study investigated how doctoral students reported their personal and professional interaction experiences that they believed might facilitate or impede their academic pursuits in biomedical research. We collected 19 in-depth interviews with doctoral students in biomedical research from eight universities, and we based our qualitative analytic approach on the work of Miles and Huberman. The results indicated that among different sources and types of interaction, academic and emotional interactions from family and teachers in various stages essentially affected students' persistence in the biomedical science field. In addition, co-mentorship among peers, departmental environment, and volunteer experiences were other essential factors. This study also found related experiences among women and underrepresented minority students that were important to their academic pursuit.

Telescience operations with the solar array module plasma interaction experiment

NASA Technical Reports Server (NTRS)

Wald, Lawrence W.; Bibyk, Irene K.

1995-01-01

The Solar Array Module Plasma Interactions Experiment (SAMPIE) is a flight experiment that flew on the Space Shuttle Columbia (STS-62) in March 1994, as part of the OAST-2 mission. The overall objective of SAMPIE was to determine the adverse environmental interactions within the space plasma of low earth orbit (LEO) on modern solar cells and space power system materials which are artificially biased to high positive and negative direct current (DC) voltages. The two environmental interactions of interest included high voltage arcing from the samples to the space plasma and parasitic current losses. High voltage arcing can cause physical damage to power system materials and shorten expected hardware life. parasitic current losses can reduce power system efficiency because electric currents generated in a power system drain into the surrounding plasma via parasitic resistance. The flight electronics included two programmable high voltage DC power supplies to bias the experiment samples, instruments to measure the surrounding plasma environment in the STS cargo bay, and the on-board data acquisition system (DAS). The DAS provided in-flight experiment control, data storage, and communications through the Goddard Space Flight Center (GSFC) Hitchhiker flight avionics to the GSFC Payload Operations Control Center (POCC). The DAS and the SAMPIE POCC computer systems were designed for telescience operations; this paper will focus on the experiences of the SAMPIE team regarding telescience development and operations from the GSFC POCC during STS-62. The SAMPIE conceptual development, hardware design, and system verification testing were accomplished at the NASA Lewis Research Center (LeRC). SAMPIE was developed under the In-Space Technology Experiment Program (IN-STEP), which sponsors NASA, industry, and university flight experiments designed to enable and enhance space flight technology. The IN-STEP Program is sponsored by the Office of Space Access and Technology (OSAT).

Interactions of dendrimers with biological drug targets: reality or mystery - a gap in drug delivery and development research.

PubMed

Ahmed, Shaimaa; Vepuri, Suresh B; Kalhapure, Rahul S; Govender, Thirumala

2016-07-21

Dendrimers have emerged as novel and efficient materials that can be used as therapeutic agents/drugs or as drug delivery carriers to enhance therapeutic outcomes. Molecular dendrimer interactions are central to their applications and realising their potential. The molecular interactions of dendrimers with drugs or other materials in drug delivery systems or drug conjugates have been extensively reported in the literature. However, despite the growing application of dendrimers as biologically active materials, research focusing on the mechanistic analysis of dendrimer interactions with therapeutic biological targets is currently lacking in the literature. This comprehensive review on dendrimers over the last 15 years therefore attempts to identify the reasons behind the apparent lack of dendrimer-receptor research and proposes approaches to address this issue. The structure, hierarchy and applications of dendrimers are briefly highlighted, followed by a review of their various applications, specifically as biologically active materials, with a focus on their interactions at the target site. It concludes with a technical guide to assist researchers on how to employ various molecular modelling and computational approaches for research on dendrimer interactions with biological targets at a molecular level. This review highlights the impact of a mechanistic analysis of dendrimer interactions on a molecular level, serves to guide and optimise their discovery as medicinal agents, and hopes to stimulate multidisciplinary research between scientific, experimental and molecular modelling research teams.

Interacting Multiple Model (IMM) Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking

PubMed Central

Liu, Hua; Wu, Wen

2017-01-01

For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF) is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM) filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF). The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF), the interacting multiple model cubature Kalman filter (IMMCKF) and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF). PMID:28608843

Interacting Multiple Model (IMM) Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking.

PubMed

Liu, Hua; Wu, Wen

2017-06-13

For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF) is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM) filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF). The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF), the interacting multiple model cubature Kalman filter (IMMCKF) and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF).

Cross-Modal Interactions in the Experience of Musical Performances: Physiological Correlates

ERIC Educational Resources Information Center

Chapados, Catherine; Levitin, Daniel J.

2008-01-01

This experiment was conducted to investigate cross-modal interactions in the emotional experience of music listeners. Previous research showed that visual information present in a musical performance is rich in expressive content, and moderates the subjective emotional experience of a participant listening and/or observing musical stimuli [Vines,…

Centrifuge impact cratering experiments: Scaling laws for non-porous targets

NASA Technical Reports Server (NTRS)

Schmidt, Robert M.

1987-01-01

A geotechnical centrifuge was used to investigate large body impacts onto planetary surfaces. At elevated gravity, it is possible to match various dimensionless similarity parameters which were shown to govern large scale impacts. Observations of crater growth and target flow fields have provided detailed and critical tests of a complete and unified scaling theory for impact cratering. Scaling estimates were determined for nonporous targets. Scaling estimates for large scale cratering in rock proposed previously by others have assumed that the crater radius is proportional to powers of the impactor energy and gravity, with no additional dependence on impact velocity. The size scaling laws determined from ongoing centrifuge experiments differ from earlier ones in three respects. First, a distinct dependence of impact velocity is recognized, even for constant impactor energy. Second, the present energy exponent for low porosity targets, like competent rock, is lower than earlier estimates. Third, the gravity exponent is recognized here as being related to both the energy and the velocity exponents.

Spectra, composition, and interactions of nuclei with magnet interaction chambers

NASA Astrophysics Data System (ADS)

Parnell, T. A.; Burnett, T. H.; Cherry, M. C.; Dake, S.; Derrickson, J. H.; Fountain, W. F.; Fuki, M.; Gregory, J. C.; Hayashi, T.; Holynski, R.; Iwai, J.; Jurak, A.; Lord, J. J.; Miyamura, O.; Niwa, K.; Oda, H.; Ogata, T.; Roberts, F. E.; Shibata, T.; Strausz, S. C.; Tabuki, T.; Taira, T.; Takahashi, Y.; Tominaga, T.; Watts, J. W.; Wefel, J. P.; Wilczynska, B.; Wilczynski, H.; Wilkes, R. J.; Wolter, W.; Wosiek, T.; Yamamoto, A.; Yokomi, H.; Yuda, T.

1990-03-01

Emulsion chambers will be flown in the Astromag Facility to measure the cosmic ray composition and spectra to 10 exp 15 eV total energy and to definitively study the characteristics of nucleus-nucleus interactions above 10 exp 12 eV/n. Two configurations of emulsion chambers will be flown in the SCIN/MAGIC experiment. One chamber has an emulsion target and a calorimeter similar to those recently flown on balloons for composition and spectra measurements. The other has an identical calorimeter and a low-density target section optimized for performing rigidity measurements on charged particles produced in interactions. The transverse momenta of charged and neutral mesons, direct hadronic pairs from resonance decays and interference effects, and possible charge clustering in high-density states of matter will be studied.

Abasic pivot substitution harnesses target specificity of RNA interference

PubMed Central

Lee, Hye-Sook; Seok, Heeyoung; Lee, Dong Ha; Ham, Juyoung; Lee, Wooje; Youm, Emilia Moonkyung; Yoo, Jin Seon; Lee, Yong-Seung; Jang, Eun-Sook; Chi, Sung Wook

2015-01-01

Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA–target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼80–100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications. PMID:26679372

OmniSearch: a semantic search system based on the Ontology for MIcroRNA Target (OMIT) for microRNA-target gene interaction data.

PubMed

Huang, Jingshan; Gutierrez, Fernando; Strachan, Harrison J; Dou, Dejing; Huang, Weili; Smith, Barry; Blake, Judith A; Eilbeck, Karen; Natale, Darren A; Lin, Yu; Wu, Bin; Silva, Nisansa de; Wang, Xiaowei; Liu, Zixing; Borchert, Glen M; Tan, Ming; Ruttenberg, Alan

2016-01-01

As a special class of non-coding RNAs (ncRNAs), microRNAs (miRNAs) perform important roles in numerous biological and pathological processes. The realization of miRNA functions depends largely on how miRNAs regulate specific target genes. It is therefore critical to identify, analyze, and cross-reference miRNA-target interactions to better explore and delineate miRNA functions. Semantic technologies can help in this regard. We previously developed a miRNA domain-specific application ontology, Ontology for MIcroRNA Target (OMIT), whose goal was to serve as a foundation for semantic annotation, data integration, and semantic search in the miRNA field. In this paper we describe our continuing effort to develop the OMIT, and demonstrate its use within a semantic search system, OmniSearch, designed to facilitate knowledge capture of miRNA-target interaction data. Important changes in the current version OMIT are summarized as: (1) following a modularized ontology design (with 2559 terms imported from the NCRO ontology); (2) encoding all 1884 human miRNAs (vs. 300 in previous versions); and (3) setting up a GitHub project site along with an issue tracker for more effective community collaboration on the ontology development. The OMIT ontology is free and open to all users, accessible at: http://purl.obolibrary.org/obo/omit.owl. The OmniSearch system is also free and open to all users, accessible at: http://omnisearch.soc.southalabama.edu/index.php/Software.

HARP targets pion production cross section and yield measurements: Implications for MiniBooNE neutrino flux

NASA Astrophysics Data System (ADS)

Wickremasinghe, Don Athula Abeyarathna

The prediction of the muon neutrino flux from a 71.0 cm long beryllium target for the MiniBooNE experiment is based on a measured pion production cross section which was taken from a short beryllium target (2.0 cm thick - 5% nuclear interaction length) in the Hadron Production (HARP) experiment at CERN. To verify the extrapolation to our longer target, HARP also measured the pion production from 20.0 cm and 40.0 cm beryllium targets. The measured production yields on targets of 50% and 100% nuclear interaction lengths in the kinematic rage of momentum from 0.75 GeV/c to 6.5 GeV/c and the range of angle from 30 mrad to 210 mrad are presented along with an update of the short target cross sections. The best fitted extended Sanford-Wang (SW) model parameterization for updated short beryllium target positive pion production cross section is presented. Yield measurements for all three targets are also compared with that from the Monte Carlo predictions in the MiniBooNE experiment for different SW parameterization. The comparisons of muon neutrino flux predictions for updated SW model is presented.

The unified database for the fixed target experiment BM@N

NASA Astrophysics Data System (ADS)

Gertsenberger, K. V.

2016-09-01

The article describes the developed database designed as comprehensive data storage of the fixed target experiment BM@N [1] at Joint Institute for Nuclear Research (JINR) in Dubna. The structure and purposes of the BM@N facility will be briefly presented. The scheme of the unified database and its parameters will be described in detail. The use of the BM@N database implemented on the PostgreSQL database management system (DBMS) allows one to provide user access to the actual information of the experiment. Also the interfaces developed for the access to the database will be presented. One was implemented as the set of C++ classes to access the data without SQL statements, the other-Web-interface being available on the Web page of the BM@N experiment.

'Living with tics': self-experience of adolescents with Tourette syndrome during peer interaction.

PubMed

Lee, Mei-Yin; Mu, Pei-Fan; Wang, Wen-Sheng; Wang, Huei-Shyong

2016-02-01

To describe the essence of the self-experience of adolescents with Tourette syndrome in the context of peer interaction. Tourette syndrome has an adverse impact on adolescents' physical, psychological and interpersonal interactions. Peers provide adolescents with social interactions that are crucial to the formation of self-identity. Studies exploring the self-experience of adolescents with Tourette syndrome in the context of peer relationships are lacking. A qualitative, phenomenological research design was used. A total of 12 adolescents with Tourette syndrome from the Taiwan Tourette Family Association were selected by purposive sampling. Data were collected using open-ended questions in one-on-one in-depth interviews that lasted 60-90 minutes. Giorgi's phenomenological methods were applied to analyse the data obtained. Four criteria were employed to evaluate methodological rigour. The findings showed that the self-experience of adolescents with Tourette syndrome during peer interaction reflected their lived experiences of peer identity, social identity and self-identity. Themes included: (1) the inexplicable onset of tics during encounters with other people, (2) sources inspiring the courage for self-acceptance and (3) strategies of self-protection in response to changes in situation. The self-experience of peer interaction among adolescents with Tourette syndrome is a dynamic and interactive process characterised by the symbolic meanings conferred on the tics by the interacting adolescents. The adolescents with Tourette syndrome obtain self-identity through peer responses and recognition, while the tolerance, respect and support of parents and teachers spark the adolescents' courage for self-acceptance. Healthcare providers who assist adolescents with Tourette syndrome must understand that tics occur in the context of peer interaction and how this affects the adolescents' relationships with their peers in various life situations. Furthermore, healthcare

Subcellular targeting and interactions among the Potato virus X TGB proteins.

PubMed

Samuels, Timmy D; Ju, Ho-Jong; Ye, Chang-Ming; Motes, Christy M; Blancaflor, Elison B; Verchot-Lubicz, Jeanmarie

2007-10-25

Potato virus X (PVX) encodes three proteins named TGBp1, TGBp2, and TGBp3 which are required for virus cell-to-cell movement. To determine whether PVX TGB proteins interact during virus cell-cell movement, GFP was fused to each TGB coding sequence within the viral genome. Confocal microscopy was used to study subcellular accumulation of each protein in virus-infected plants and protoplasts. GFP:TGBp2 and TGBp3:GFP were both seen in the ER, ER-associated granular vesicles, and perinuclear X-bodies suggesting that these proteins interact in the same subdomains of the endomembrane network. When plasmids expressing CFP:TGBp2 and TGBp3:GFP were co-delivered to tobacco leaf epidermal cells, the fluorescent signals overlapped in ER-associated granular vesicles indicating that these proteins colocalize in this subcellular compartment. GFP:TGBp1 was seen in the nucleus, cytoplasm, rod-like inclusion bodies, and in punctate sites embedded in the cell wall. The puncta were reminiscent of previous reports showing viral proteins in plasmodesmata. Experiments using CFP:TGBp1 and YFP:TGBp2 or TGBp3:GFP showed CFP:TGBp1 remained in the cytoplasm surrounding the endomembrane network. There was no evidence that the granular vesicles contained TGBp1. Yeast two hybrid experiments showed TGBp1 self associates but failed to detect interactions between TGBp1 and TGBp2 or TGBp3. These experiments indicate that the PVX TGB proteins have complex subcellular accumulation patterns and likely cooperate across subcellular compartments to promote virus infection.

Nonlinear interaction of strong microwave beam with the ionosphere MINIX rocket experiment

NASA Astrophysics Data System (ADS)

Kaya, N.; Matsumoto, H.; Miyatake, S.; Kimura, I.; Nagatomo, M.

A rocket-borne experiment called 'MINIX' was carried out to investigate the nonlinear interaction of a strong microwave energy beam with the ionosphere. The MINIX stands for Microwave-Ionosphere Nonlinear Interaction eXperiment and was carried out on August 29, 1983. The objective of the MINIX is to study possible impacts of the SPS microwave energy beam on the ionosphere, such as the ohmic heating and plasma wave excitation. The experiment showed that the microwave with f = 2.45 GHz nonlinearly excites various electrostatic plasma waves, though no ohmic heating effects were detected.

Impact of fluid-structure interaction on direct tumor-targeting in a representative hepatic artery system.

PubMed

Childress, Emily M; Kleinstreuer, Clement

2014-03-01

Direct targeting of solid tumors with chemotherapeutic drugs and/or radioactive microspheres can be a treatment option which minimizes side-effects and reduces cost. Briefly, computational analysis generates particle release maps (PRMs) which visually link upstream particle injection regions in the main artery with associated exit branches, some connected to tumors. The overall goal is to compute patient-specific PRMs realistically, accurately, and cost-effectively, which determines the suitable radial placement of a micro-catheter for optimal particle injection. Focusing in this paper on new steps towards realism and accuracy, the impact of fluid-structure interaction on direct drug-targeting is evaluated, using a representative hepatic artery system with liver tumor as a test bed. Specifically, the effect of arterial wall motion was demonstrated by modeling a two-way fluid-structure interaction analysis with Lagrangian particle tracking in the bifurcating arterial system. Clearly, rapid computational evaluation of optimal catheter location for tumor-targeting in a clinical application is very important. Hence, rigid-wall cases were also compared to the flexible scenario to establish whether PRMs generated when based on simplifying assumptions could provide adequate guidance towards ideal catheter placement. It was found that the best rigid (i.e., time-averaged) geometry is the physiological one that occurs during the diastolic targeting interval.

Interaction of Herbal Compounds with Biological Targets: A Case Study with Berberine

PubMed Central

Chen, Xiao-Wu; Di, Yuan Ming; Zhang, Jian; Zhou, Zhi-Wei; Li, Chun Guang; Zhou, Shu-Feng

2012-01-01

Berberine is one of the main alkaloids found in the Chinese herb Huang lian (Rhizoma Coptidis), which has been reported to have multiple pharmacological activities. This study aimed to analyze the molecular targets of berberine based on literature data followed by a pathway analysis using the PANTHER program. PANTHER analysis of berberine targets showed that the most classes of molecular functions include receptor binding, kinase activity, protein binding, transcription activity, DNA binding, and kinase regulator activity. Based on the biological process classification of in vitro berberine targets, those targets related to signal transduction, intracellular signalling cascade, cell surface receptor-linked signal transduction, cell motion, cell cycle control, immunity system process, and protein metabolic process are most frequently involved. In addition, berberine was found to interact with a mixture of biological pathways, such as Alzheimer's disease-presenilin and -secretase pathways, angiogenesis, apoptosis signalling pathway, FAS signalling pathway, Hungtington disease, inflammation mediated by chemokine and cytokine signalling pathways, interleukin signalling pathway, and p53 pathways. We also explored the possible mechanism of action for the anti-diabetic effect of berberine. Further studies are warranted to elucidate the mechanisms of action of berberine using systems biology approach. PMID:23213296

Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference

PubMed Central

Jiang, Jing; Lu, Weiqiang; Li, Weihua; Liu, Guixia; Zhou, Weixing; Huang, Jin; Tang, Yun

2012-01-01

Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning. PMID:22589709

Overview on the target fabrication facilities at ELI-NP and ongoing strategies

NASA Astrophysics Data System (ADS)

Gheorghiu, C. C.; Leca, V.; Popa, D.; Cernaianu, M. O.; Stutman, D.

2016-10-01

Along with the development of petawatt class laser systems, the interaction between high power lasers and matter flourished an extensive research, with high-interest applications like: laser nuclear physics, proton radiography or cancer therapy. The new ELI-NP (Extreme Light Infrastructure - Nuclear Physics) petawatt laser facility, with 10PW and ~ 1023W/cm2 beam intensity, is one of the innovative projects that will provide novel research of fundamental processes during light-matter interaction. As part of the ELI-NP facility, Targets Laboratory will provide the means for in-house manufacturing and characterization of the required targets (mainly solid ones) for the experiments, in addition to the research activity carried out in order to develop novel target designs with improved performances. A description of the Targets Laboratory with the main pieces of equipment and their specifications are presented. Moreover, in view of the latest progress in the target design, one of the proposed strategies for the forthcoming experiments at ELI-NP is also described, namely: ultra-thin patterned foil of diamond-like carbon (DLC) coated with a carbon-based ultra-low density layer. The carbon foam which behaves as a near-critical density plasma, will allow the controlled-shaping of the laser pulse before the main interaction with the solid foil. Particular emphasis will be directed towards the target's design optimization, by simulation tests and tuning the key-properties (thickness/length, spacing, density foam, depth, periodicity etc.) which are expected to have a crucial effect on the laser-matter interaction process.

Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors.

PubMed

Suebsuwong, Chalada; Pinkas, Daniel M; Ray, Soumya S; Bufton, Joshua C; Dai, Bing; Bullock, Alex N; Degterev, Alexei; Cuny, Gregory D

2018-02-15

Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pan-kinase inhibitor regorafenib that aim to engage basic activation loop residues Lys169 or Arg171. We report development of CSR35 that displayed >10-fold selective inhibition of RIPK2 versus VEGFR2, the target of regorafenib. A co-crystal structure of CSR35 with RIPK2 revealed a resolved activation loop with an ionic interaction between the carboxylic acid installed in the inhibitor and the side-chain of Lys169. Our data provides principle feasibility of developing activation loop targeting type II inhibitors as a complementary strategy for achieving improved selectivity. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

On wind-wave-current interactions during the Shoaling Waves Experiment

NASA Astrophysics Data System (ADS)

Zhang, Fei W.; Drennan, William M.; Haus, Brian K.; Graber, Hans C.

2009-01-01

This paper presents a case study of wind-wave-current interaction during the Shoaling Waves Experiment (SHOWEX). Surface current fields off Duck, North Carolina, were measured by a high-frequency Ocean Surface Current Radar (OSCR). Wind, wind stress, and directional wave data were obtained from several Air Sea Interaction Spar (ASIS) buoys moored in the OSCR scanning domain. At several times during the experiment, significant coastal currents entered the experimental area. High horizontal shears at the current edge resulted in the waves at the peak of wind-sea spectra (but not those in the higher-frequency equilibrium range) being shifted away from the mean wind direction. This led to a significant turning of the wind stress vector away from the mean wind direction. The interactions presented here have important applications in radar remote sensing and are discussed in the context of recent radar imaging models of the ocean surface.

Addressing Issues of Workplace Harassment: Counseling the Targets.

ERIC Educational Resources Information Center

Lewis, Jacqueline; Coursol, Diane; Wahl, Kay Herting

2002-01-01

Workplace harassment includes dysfunctional personal interactions characterized by bullying behaviors, personal attacks, and attempts to denigrate others. Targets of workplace harassment may experience stress, depression, low self-esteem, loss of sleep, and even posttraumatic stress disorder. Strategies that counselors can use to work effectively…

An Improved Interacting Multiple Model Filtering Algorithm Based on the Cubature Kalman Filter for Maneuvering Target Tracking.

PubMed

Zhu, Wei; Wang, Wei; Yuan, Gannan

2016-06-01

In order to improve the tracking accuracy, model estimation accuracy and quick response of multiple model maneuvering target tracking, the interacting multiple models five degree cubature Kalman filter (IMM5CKF) is proposed in this paper. In the proposed algorithm, the interacting multiple models (IMM) algorithm processes all the models through a Markov Chain to simultaneously enhance the model tracking accuracy of target tracking. Then a five degree cubature Kalman filter (5CKF) evaluates the surface integral by a higher but deterministic odd ordered spherical cubature rule to improve the tracking accuracy and the model switch sensitivity of the IMM algorithm. Finally, the simulation results demonstrate that the proposed algorithm exhibits quick and smooth switching when disposing different maneuver models, and it also performs better than the interacting multiple models cubature Kalman filter (IMMCKF), interacting multiple models unscented Kalman filter (IMMUKF), 5CKF and the optimal mode transition matrix IMM (OMTM-IMM).

Interaction of prime and target in the subliminal affective priming effect.

PubMed

Haneda, Kaoruko; Nomura, Michio; Iidaka, Tetsuya; Ohira, Hideki

2003-04-01

It has been found that an emotional stimulus such as a facial expression presented subliminally can affect subsequent information processing and behavior, usually by shifting evaluation of a subsequent stimulus to a valence congruent with the previous stimulus. This phenomenon is called subliminal affective priming. The present study was conducted to replicate and expand previous findings by investigating interaction of primes and targets in the affective priming effect. Two conditions were used. Prime (subliminal presentation 35 msec.) of an angry face of a woman and a No Prime control condition. Just after presentation of the prime, an ambiguous angry face or an emotionally neutral face was presented above the threshold of awareness (500 msec.). 12 female undergraduate women judged categories of facial expressions (Anger, Neutral, or Happiness) for the target faces. Analysis indicated that the Anger primes significantly facilitated judgment of anger for the ambiguous angry faces; however, the priming effect of the Anger primes was not observed for neutral faces. Consequently, the present finding suggested that a subliminal affective priming effect should be more prominent when affective valence of primes and targets is congruent.

A Small-molecule Inhibitor, 5′-O-Tritylthymidine, targets FAK and Mdm-2 Interaction, and Blocks Breast and Colon Tumorigenesis in vivo

PubMed Central

Golubovskaya, Vita; Palma, Nadia L.; Zheng, Min; Ho, Baotran; Magis, Andrew; Ostrov, David; Cance, William G.

2013-01-01

Focal Adhesion Kinase (FAK) is overexpressed in many types of tumors and plays an important role in survival. We developed a novel approach, targeting FAK-protein interactions by computer modeling and screening of NCI small molecule drug database. In this report we targeted FAK and Mdm-2 protein interaction to decrease tumor growth. By macromolecular modeling we found a model of FAK and Mdm-2 interaction and performed screening of >200,000 small molecule compounds from NCI database with drug-like characteristics, targeting the FAK-Mdm-2 interaction. We identified 5′-O-Tritylthymidine, called M13 compound that significantly decreased viability in different cancer cells. M13 was docked into the pocket of FAK and Mdm-2 interaction and was directly bound to the FAK-N terminal domain by ForteBio Octet assay. In addition, M13 compound affected FAK and Mdm-2 levels and decreased complex of FAK and Mdm-2 proteins in breast and colon cancer cells. M13 re-activated p53 activity inhibited by FAK with Mdm-2 promoter. M13 decreased viability, clonogenicity, increased detachment and apoptosis in a dose-dependent manner in BT474 breast and in HCT116 colon cancer cells in vitro. M13 decreased FAK, activated p53 and caspase-8 in both cell lines. In addition, M13 decreased breast and colon tumor growth in vivo. M13 activated p53 and decreased FAK in tumor samples consistent with decreased tumor growth. The data demonstrate a novel approach for targeting FAK and Mdm-2 protein interaction, provide a model of FAK and Mdm-2 interaction, identify M13 compound targeting this interaction and decreasing tumor growth that is critical for future targeted therapeutics. PMID:22292771

The eccentricity effect: target eccentricity affects performance on conjunction searches.

PubMed

Carrasco, M; Evert, D L; Chang, I; Katz, S M

1995-11-01

The serial pattern found for conjunction visual-search tasks has been attributed to covert attentional shifts, even though the possible contributions of target location have not been considered. To investigate the effect of target location on orientation x color conjunction searches, the target's duration and its position in the display were manipulated. The display was present either until observers responded (Experiment 1), for 104 msec (Experiment 2), or for 62 msec (Experiment 3). Target eccentricity critically affected performance: A pronounced eccentricity effect was very similar for all three experiments; as eccentricity increased, reaction times and errors increased gradually. Furthermore, the set-size effect became more pronounced as target eccentricity increased, and the extent of the eccentricity effect increased for larger set sizes. In addition, according to stepwise regressions, target eccentricity as well as its interaction with set size were good predictors of performance. We suggest that these findings could be explained by spatial-resolution and lateral-inhibition factors. The serial self-terminating hypothesis for orientation x color conjunction searches was evaluated and rejected. We compared the eccentricity effect as well as the extent of the orientation asymmetry in these three conjunction experiments with those found in feature experiments (Carrasco & Katz, 1992). The roles of eye movements, spatial resolution, and covert attention in the eccentricity effect, as well as their implications, are discussed.

Solvent-Ion Interactions in Salt Water: A Simple Experiment.

ERIC Educational Resources Information Center

Willey, Joan D.

1984-01-01

Describes a procedurally quick, simple, and inexpensive experiment which illustrates the magnitude and some effects of solvent-ion interactions in aqueous solutions. Theoretical information, procedures, and examples of temperature, volume and hydration number calculations are provided. (JN)

C-SPADE: a web-tool for interactive analysis and visualization of drug screening experiments through compound-specific bioactivity dendrograms

PubMed Central

Alam, Zaid; Peddinti, Gopal

2017-01-01

Abstract The advent of polypharmacology paradigm in drug discovery calls for novel chemoinformatic tools for analyzing compounds’ multi-targeting activities. Such tools should provide an intuitive representation of the chemical space through capturing and visualizing underlying patterns of compound similarities linked to their polypharmacological effects. Most of the existing compound-centric chemoinformatics tools lack interactive options and user interfaces that are critical for the real-time needs of chemical biologists carrying out compound screening experiments. Toward that end, we introduce C-SPADE, an open-source exploratory web-tool for interactive analysis and visualization of drug profiling assays (biochemical, cell-based or cell-free) using compound-centric similarity clustering. C-SPADE allows the users to visually map the chemical diversity of a screening panel, explore investigational compounds in terms of their similarity to the screening panel, perform polypharmacological analyses and guide drug-target interaction predictions. C-SPADE requires only the raw drug profiling data as input, and it automatically retrieves the structural information and constructs the compound clusters in real-time, thereby reducing the time required for manual analysis in drug development or repurposing applications. The web-tool provides a customizable visual workspace that can either be downloaded as figure or Newick tree file or shared as a hyperlink with other users. C-SPADE is freely available at http://cspade.fimm.fi/. PMID:28472495

[Experience of knowledge translation in the ITSAL (immigration, work and health) research project with representatives of the target population].

PubMed

Ronda, Elena; López-Jacob, M José; Paredes-Carbonell, Joan J; López, Pilar; Boix, Pere; García, Ana M

2014-01-01

This article describes the experience of knowledge translation between researchers of the ITSAL (immigration, work and health) project and representatives of organizations working with immigrants to discuss the results obtained in the project and future research lines. A meeting was held, attended by three researchers and 18 representatives from 11 institutions. Following a presentation of the methodology and results of the project, the participants discussed the results presented and research areas of interest, thus confirming matches between the two sides and obtaining proposals of interest for the ITSAL project. We understand the process described as an approach to social validation of some of the main results of this project. This experience has allowed us to open a channel of communication with the target population of the study, in line with the necessary two-way interaction between researchers and users. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

NASA Astrophysics Data System (ADS)

Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

2015-11-01

Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

Wave-Sediment Interaction in Muddy Environments: A Field Experiment

DTIC Science & Technology

2007-01-01

in Years 1 and 2 (2007-2008) and a data analysis and modeling effort in Year 3 (2009). 2. “A System for Monitoring Wave-Sediment Interaction in...project was to conduct a pilot field experiment to test instrumentation and data analysis procedures for the major field experiment effort scheduled in...Chou et al., 1993; Foda et al., 1993). With the exception of liquefaction processes, these models assume a single, well- defined mud phase

Cartilage-targeting drug delivery: can electrostatic interactions help?

PubMed

Bajpayee, Ambika G; Grodzinsky, Alan J

2017-03-01

Current intra-articular drug delivery methods do not guarantee sufficient drug penetration into cartilage tissue to reach cell and matrix targets at the concentrations necessary to elicit the desired biological response. Here, we provide our perspective on the utilization of charge-charge (electrostatic) interactions to enhance drug penetration and transport into cartilage, and to enable sustained binding of drugs within the tissue's highly negatively charged extracellular matrix. By coupling drugs to positively charged nanocarriers that have optimal size and charge, cartilage can be converted from a drug barrier into a drug reservoir for sustained intra-tissue delivery. Alternatively, a wide variety of drugs themselves can be made cartilage-penetrating by functionalizing them with specialized positively charged protein domains. Finally, we emphasize that appropriate animal models, with cartilage thickness similar to that of humans, must be used for the study of drug transport and retention in cartilage.

Discovery: an interactive resource for the rational selection and comparison of putative drug target proteins in malaria

PubMed Central

Joubert, Fourie; Harrison, Claudia M; Koegelenberg, Riaan J; Odendaal, Christiaan J; de Beer, Tjaart AP

2009-01-01

Background Up to half a billion human clinical cases of malaria are reported each year, resulting in about 2.7 million deaths, most of which occur in sub-Saharan Africa. Due to the over-and misuse of anti-malarials, widespread resistance to all the known drugs is increasing at an alarming rate. Rational methods to select new drug target proteins and lead compounds are urgently needed. The Discovery system provides data mining functionality on extensive annotations of five malaria species together with the human and mosquito hosts, enabling the selection of new targets based on multiple protein and ligand properties. Methods A web-based system was developed where researchers are able to mine information on malaria proteins and predicted ligands, as well as perform comparisons to the human and mosquito host characteristics. Protein features used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein interactions, protein-ligand interactions and host-pathogen interactions among others. Searching by chemical structure is also available. Results An in silico system for the selection of putative drug targets and lead compounds is presented, together with an example study on the bifunctional DHFR-TS from Plasmodium falciparum. Conclusion The Discovery system allows for the identification of putative drug targets and lead compounds in Plasmodium species based on the filtering of protein and chemical properties. PMID:19642978

The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery.

PubMed

Lamotte, Suzanne; Späth, Gerald F; Rachidi, Najma; Prina, Eric

2017-06-01

The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites' intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host-parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.

Flow Experiences of Children in an Interactive Social Game Environment

ERIC Educational Resources Information Center

Inal, Yavuz; Cagiltay, Kursat

2007-01-01

This study examines children's flow experiences in an interactive social game environment. A total of 33 children aged from 7 to 9 years participated in the study for 6 weeks. Data were collected through observations and interviews. In order to measure the flow experiences of the children, items of a flow scale were administered to the children…

The DESI Experiment Part I: Science,Targeting, and Survey Design

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

Aghamousa, Amir; et al.

DESI (Dark Energy Spectroscopic Instrument) is a Stage IV ground-based dark energy experiment that will study baryon acoustic oscillations (BAO) and the growth of structure through redshift-space distortions with a wide-area galaxy and quasar redshift survey. To trace the underlying dark matter distribution, spectroscopic targets will be selected in four classes from imaging data. We will measure luminous red galaxies up tomore » $z=1.0$. To probe the Universe out to even higher redshift, DESI will target bright [O II] emission line galaxies up to $z=1.7$. Quasars will be targeted both as direct tracers of the underlying dark matter distribution and, at higher redshifts ($ 2.1 < z < 3.5$), for the Ly-$$\\alpha$$ forest absorption features in their spectra, which will be used to trace the distribution of neutral hydrogen. When moonlight prevents efficient observations of the faint targets of the baseline survey, DESI will conduct a magnitude-limited Bright Galaxy Survey comprising approximately 10 million galaxies with a median $$z\\approx 0.2$$. In total, more than 30 million galaxy and quasar redshifts will be obtained to measure the BAO feature and determine the matter power spectrum, including redshift space distortions.« less

The experience of agency in human-computer interactions: a review

PubMed Central

Limerick, Hannah; Coyle, David; Moore, James W.

2014-01-01

The sense of agency is the experience of controlling both one’s body and the external environment. Although the sense of agency has been studied extensively, there is a paucity of studies in applied “real-life” situations. One applied domain that seems highly relevant is human-computer-interaction (HCI), as an increasing number of our everyday agentive interactions involve technology. Indeed, HCI has long recognized the feeling of control as a key factor in how people experience interactions with technology. The aim of this review is to summarize and examine the possible links between sense of agency and understanding control in HCI. We explore the overlap between HCI and sense of agency for computer input modalities and system feedback, computer assistance, and joint actions between humans and computers. An overarching consideration is how agency research can inform HCI and vice versa. Finally, we discuss the potential ethical implications of personal responsibility in an ever-increasing society of technology users and intelligent machine interfaces. PMID:25191256

Interaction between numbers and size during visual search.

PubMed

Krause, Florian; Bekkering, Harold; Pratt, Jay; Lindemann, Oliver

2017-05-01

The current study investigates an interaction between numbers and physical size (i.e. size congruity) in visual search. In three experiments, participants had to detect a physically large (or small) target item among physically small (or large) distractors in a search task comprising single-digit numbers. The relative numerical size of the digits was varied, such that the target item was either among the numerically large or small numbers in the search display and the relation between numerical and physical size was either congruent or incongruent. Perceptual differences of the stimuli were controlled by a condition in which participants had to search for a differently coloured target item with the same physical size and by the usage of LCD-style numbers that were matched in visual similarity by shape transformations. The results of all three experiments consistently revealed that detecting a physically large target item is significantly faster when the numerical size of the target item is large as well (congruent), compared to when it is small (incongruent). This novel finding of a size congruity effect in visual search demonstrates an interaction between numerical and physical size in an experimental setting beyond typically used binary comparison tasks, and provides important new evidence for the notion of shared cognitive codes for numbers and sensorimotor magnitudes. Theoretical consequences for recent models on attention, magnitude representation and their interactions are discussed.

Target identification in Fusobacterium nucleatum by subtractive genomics approach and enrichment analysis of host-pathogen protein-protein interactions.

PubMed

Kumar, Amit; Thotakura, Pragna Lakshmi; Tiwary, Basant Kumar; Krishna, Ramadas

2016-05-12

Fusobacterium nucleatum, a well studied bacterium in periodontal diseases, appendicitis, gingivitis, osteomyelitis and pregnancy complications has recently gained attention due to its association with colorectal cancer (CRC) progression. Treatment with berberine was shown to reverse F. nucleatum-induced CRC progression in mice by balancing the growth of opportunistic pathogens in tumor microenvironment. Intestinal microbiota imbalance and the infections caused by F. nucleatum might be regulated by therapeutic intervention. Hence, we aimed to predict drug target proteins in F. nucleatum, through subtractive genomics approach and host-pathogen protein-protein interactions (HP-PPIs). We also carried out enrichment analysis of host interacting partners to hypothesize the possible mechanisms involved in CRC progression due to F. nucleatum. In subtractive genomics approach, the essential, virulence and resistance related proteins were retrieved from RefSeq proteome of F. nucleatum by searching against Database of Essential Genes (DEG), Virulence Factor Database (VFDB) and Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT) tool respectively. A subsequent hierarchical screening to identify non-human homologous, metabolic pathway-independent/pathway-specific and druggable proteins resulted in eight pathway-independent and 27 pathway-specific druggable targets. Co-aggregation of F. nucleatum with host induces proinflammatory gene expression thereby potentiates tumorigenesis. Hence, proteins from IBDsite, a database for inflammatory bowel disease (IBD) research and those involved in colorectal adenocarcinoma as interpreted from The Cancer Genome Atlas (TCGA) were retrieved to predict drug targets based on HP-PPIs with F. nucleatum proteome. Prediction of HP-PPIs exhibited 186 interactions contributed by 103 host and 76 bacterial proteins. Bacterial interacting partners were accounted as putative targets. And enrichment analysis of host interacting partners showed statistically

Structure-Based Analysis Reveals Cancer Missense Mutations Target Protein Interaction Interfaces.

PubMed

Engin, H Billur; Kreisberg, Jason F; Carter, Hannah

2016-01-01

Recently it has been shown that cancer mutations selectively target protein-protein interactions. We hypothesized that mutations affecting distinct protein interactions involving established cancer genes could contribute to tumor heterogeneity, and that novel mechanistic insights might be gained into tumorigenesis by investigating protein interactions under positive selection in cancer. To identify protein interactions under positive selection in cancer, we mapped over 1.2 million nonsynonymous somatic cancer mutations onto 4,896 experimentally determined protein structures and analyzed their spatial distribution. In total, 20% of mutations on the surface of known cancer genes perturbed protein-protein interactions (PPIs), and this enrichment for PPI interfaces was observed for both tumor suppressors (Odds Ratio 1.28, P-value < 10(-4)) and oncogenes (Odds Ratio 1.17, P-value < 10(-3)). To study this further, we constructed a bipartite network representing structurally resolved PPIs from all available human complexes in the Protein Data Bank (2,864 proteins, 3,072 PPIs). Analysis of frequently mutated cancer genes within this network revealed that tumor-suppressors, but not oncogenes, are significantly enriched with functional mutations in homo-oligomerization regions (Odds Ratio 3.68, P-Value < 10(-8)). We present two important examples, TP53 and beta-2-microglobulin, for which the patterns of somatic mutations at interfaces provide insights into specifically perturbed biological circuits. In patients with TP53 mutations, patient survival correlated with the specific interactions that were perturbed. Moreover, we investigated mutations at the interface of protein-nucleotide interactions and observed an unexpected number of missense mutations but not silent mutations occurring within DNA and RNA binding sites. Finally, we provide a resource of 3,072 PPI interfaces ranked according to their mutation rates. Analysis of this list highlights 282 novel candidate cancer

Ideology and gender: observers' system justification and targets' gender as interactive predictors of citizenship expectations.

PubMed

Chiaburu, Dan S; Harris, T Brad; Smith, Troy A

2014-01-01

We integrate system justification and social role theory to explain how observers' system justification and target employees' gender interact to predict observers' expectations of targets' sportsmanship citizenship behaviors. In contrast with social role theory predictions, observers did not expect greater levels of sportsmanship from women compared to men. Yet observers expected more sportsmanship from women (a) when observers were ideologically motivated by gender-specific beliefs (gender-specific system justification; Study 1) and (b) when system justification was cued experimentally (Study 2). A heretofore-unexamined aspect, observers' ideology, modifies their expectations of sportsmanship citizenship across target genders. This has implications for system justification, social role, and organizational citizenship theoretical perspectives.

Analysis of protein targets in pathogen-host interaction in infectious diseases: a case study on Plasmodium falciparum and Homo sapiens interaction network.

PubMed

Saha, Sovan; Sengupta, Kaustav; Chatterjee, Piyali; Basu, Subhadip; Nasipuri, Mita

2017-09-23

Infection and disease progression is the outcome of protein interactions between pathogen and host. Pathogen, the role player of Infection, is becoming a severe threat to life as because of its adaptability toward drugs and evolutionary dynamism in nature. Identifying protein targets by analyzing protein interactions between host and pathogen is the key point. Proteins with higher degree and possessing some topologically significant graph theoretical measures are found to be drug targets. On the other hand, exceptional nodes may be involved in infection mechanism because of some pathway process and biologically unknown factors. In this article, we attempt to investigate characteristics of host-pathogen protein interactions by presenting a comprehensive review of computational approaches applied on different infectious diseases. As an illustration, we have analyzed a case study on infectious disease malaria, with its causative agent Plasmodium falciparum acting as 'Bait' and host, Homo sapiens/human acting as 'Prey'. In this pathogen-host interaction network based on some interconnectivity and centrality properties, proteins are viewed as central, peripheral, hub and non-hub nodes and their significance on infection process. Besides, it is observed that because of sparseness of the pathogen and host interaction network, there may be some topologically unimportant but biologically significant proteins, which can also act as Bait/Prey. So, functional similarity or gene ontology mapping can help us in this case to identify these proteins. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Study of Multiplicities in Hadronic Interactions (in Spanish)

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

Estrada Tristan, Nora Patricia; /San Luis Potosi U.

Using data from the SELEX (Fermilab E781) experiment obtained with a minimum-bias trigger, we study multiplicity and angular distributions of secondary particles produced in interactions in the experimental targets. We observe interactions of {Sigma}{sup -}, proton, {pi}{sup -}, and {pi}{sup +}, at beam momenta between 250 GeV/c and 650 GeV/c, in copper, polyethylene, graphite, and beryllium targets. We show that the multiplicity and angular distributions for meson and baryon beams at the same momentum are identical. We also show that the mean multiplicity increases with beam momentum, and presents only small variations with the target material.

HARP targets pion production cross section and yield measurements. Implications for MiniBooNE neutrino flux

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

Wickremasinghe, Don Athula Abeyarathna

2015-07-01

The prediction of the muon neutrino flux from a 71.0 cm long beryllium target for the MiniBooNE experiment is based on a measured pion production cross section which was taken from a short beryllium target (2.0 cm thick - 5% nuclear interaction length) in the Hadron Production (HARP) experiment at CERN. To verify the extrapolation to our longer target, HARP also measured the pion production from 20.0 cm and 40.0 cm beryllium targets. The measured production yields, d 2N π± (p; θ )=dpd Ω, on targets of 50% and 100% nuclear interaction lengths in the kinematic rage of momentum frommore » 0.75 GeV/c to 6.5 GeV/c and the range of angle from 30 mrad to 210 mrad are presented along with an update of the short target cross sections. The best fitted extended Sanford-Wang (SW) model parameterization for updated short beryllium target π + production cross section is presented. Yield measurements for all three targets are also compared with that from the Monte Carlo predictions in the MiniBooNE experiment for different SW parameterization. The comparisons of v μ flux predictions for updated SW model is presented.« less

Image-Based Multi-Target Tracking through Multi-Bernoulli Filtering with Interactive Likelihoods.

PubMed

Hoak, Anthony; Medeiros, Henry; Povinelli, Richard J

2017-03-03

We develop an interactive likelihood (ILH) for sequential Monte Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, Australian Rules Football League (AFL) and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (optimal sub-pattern assignment (OSPA) and classification of events, activities and relationships for multi-object trackers (CLEAR MOT)). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter.

Image-Based Multi-Target Tracking through Multi-Bernoulli Filtering with Interactive Likelihoods

PubMed Central

Hoak, Anthony; Medeiros, Henry; Povinelli, Richard J.

2017-01-01

We develop an interactive likelihood (ILH) for sequential Monte Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, Australian Rules Football League (AFL) and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (optimal sub-pattern assignment (OSPA) and classification of events, activities and relationships for multi-object trackers (CLEAR MOT)). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter. PMID:28273796

Nanosized Drug Delivery Systems in Gastrointestinal Targeting: Interactions with Microbiota

PubMed Central

Karavolos, Michail; Holban, Alina

2016-01-01

The new age of nanotechnology has signaled a stream of entrepreneurial possibilities in various areas, form industry to medicine. Drug delivery has benefited the most by introducing nanostructured systems in the transport and controlled release of therapeutic molecules at targeted sites associated with a particular disease. As many nanosized particles reach the gastrointestinal tract by various means, their interactions with the molecular components of this highly active niche are intensively investigated. The well-characterized antimicrobial activities of numerous nanoparticles are currently being considered as a reliable and efficient alternative to the eminent world crisis in antimicrobial drug discovery. The interactions of nanosystems present in the gastrointestinal route with host microbiota is unavoidable; hence, a major research initiative is needed to explore the mechanisms and effects of these nanomaterials on microbiota and the impact that microbiota may have in the outcome of therapies entailing drug delivery nanosystems through the gastrointestinal route. These coordinated studies will provide novel techniques to replace or act synergistically with current technologies and help develop new treatments for major diseases via the discovery of unique antimicrobial molecules. PMID:27690060

Experiment for validation of fluid-structure interaction models and algorithms.

PubMed

Hessenthaler, A; Gaddum, N R; Holub, O; Sinkus, R; Röhrle, O; Nordsletten, D

2017-09-01

In this paper a fluid-structure interaction (FSI) experiment is presented. The aim of this experiment is to provide a challenging yet easy-to-setup FSI test case that addresses the need for rigorous testing of FSI algorithms and modeling frameworks. Steady-state and periodic steady-state test cases with constant and periodic inflow were established. Focus of the experiment is on biomedical engineering applications with flow being in the laminar regime with Reynolds numbers 1283 and 651. Flow and solid domains were defined using computer-aided design (CAD) tools. The experimental design aimed at providing a straightforward boundary condition definition. Material parameters and mechanical response of a moderately viscous Newtonian fluid and a nonlinear incompressible solid were experimentally determined. A comprehensive data set was acquired by using magnetic resonance imaging to record the interaction between the fluid and the solid, quantifying flow and solid motion. Copyright © 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

Participate or Observe? Effects of Economic Classroom Experiments on Students' Economic Literacy

ERIC Educational Resources Information Center

Grol, Roel; Sent, Esther-Mirjam; de Vries, Bregje

2017-01-01

Economic classroom experiments are controlled interactive learning exercises targeting the comprehension of economic concepts in an inductive way. Aiming at increasing students' knowledge of economic concepts, two types of economic classroom experiments are examined in a sample of 134 secondary school students. In the interactive research…

Time-Space Position of Warm Dense Matter in Laser Plasma Interaction Process

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

Cao, L F; Uschmann, I; Forster, E

2006-09-25

Laser plasma interaction experiments have been perform performed using an fs Titanium Sapphire laser. Plasmas have been generated from planar PMMA targets using single laser pulses with 3.3 mJ pulse energy, 50 fs pulse duration at 800 nm wavelength. Electron density distributions of the plasmas in different delay times have been characterized by means of Nomarski Interferometry. Experimental data were cautiously compared with relevant 1D numerical simulation. Finally these results provide a first experience of searching for the time-space position of the so-called warm dense plasma in an ultra fast laser target interaction process. These experiments aim to prepare nearmore » solid-density plasmas for Thomson scattering experiments using the short wavelength free-electron laser FLASH, DESY Hamburg.« less

The effect of an interactive experience on music majors' perceptions of music for deaf students.

PubMed

Kaiser, K A; Johnson, K E

2000-01-01

The purpose of this study was to examine the effect of an interactive experience on music majors' perceptions of music experiences for deaf students. Twenty-three members of a pre-existing college brass ensemble served as subjects, and a 1-hour interactive concert/presentation for 10 deaf elementary children served as the independent variable. The interactive experience was designed to provide social, musical, and educational interactions between the college musicians and the deaf children. A pretest-posttest design was utilized, and the dependent variable was a questionnaire designed to examine the subjects' perceptions regarding music for deaf students, including how prepared, comfortable, and willing they felt to provide music experiences for deaf students. Results reveal that this single interactive experience had a significant effect on the subjects' perceptions of the value of music in the education of deaf children (p <.05). Although the pretest and posttest scores indicate that the subjects felt apprehensive about their preparedness to work with deaf students, the subjects felt significantly more positive about their preparedness following the interaction (p <.001). An analysis of open comments indicates that the subjects perceived the experience as (a) very positive, (b) increasing their knowledge and perception of music for deaf students, (c) helping them better relate to the deaf population, (d) promoting interest in similar experiences and in gaining more information, and (e) eliciting a feeling that future teachers should have similar experiences. Quotes from the subjects are given, and implications for teacher training/music therapy programs are discussed.

The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery

PubMed Central

Späth, Gerald F.; Rachidi, Najma; Prina, Eric

2017-01-01

The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival. PMID:28594938

Learning Experiences in a Giant Interactive Environment: Insights from The Cube

ERIC Educational Resources Information Center

Stoodley, Ian; Sayyad Abdi, Elham; Bruce, Christine; Hughes, Hilary

2018-01-01

In November 2012, Queensland University of Technology in Australia launched a giant interactive learning environment known as "The Cube". This article reports a phenomenographic investigation into visitors' different experiences of learning in The Cube. At present very little is known about people's learning experience in spaces…

C-SIDE: The control-structure interaction demonstration experiment

NASA Technical Reports Server (NTRS)

Mohl, James B.; Davis, Hugh W.

1993-01-01

The Control-Structure Interaction Demonstration Experiment (C-SIDE) is sponsored by the Electro-Optics and Cryogenics Division of Ball Aerospace Systems Group. Our objective is to demonstrate methods of solution to structure control problems utilizing currently available hardware in a system that is an extension of our corporate experience. The larger space structures with which Ball has been associated are the SEASAT radar antenna, Shuttle Imaging Radar (SIR) -A, -B and -C antennas and the Radarsat spacecraft. The motivation for the C-SIDE configuration is to show that integration of active figure control in the radar's system-level design can relieve antenna mechanical design constraints. This presentation is primarily an introduction to the C-SIDE testbed. Its physical and functional layouts, and major components are described. The sensor is of special interest as it enables direct surface figure measurements from a remote location. The Remote Attitude Measurement System (RAMS) makes high-rate, unobtrusive measurements of many locations, several of which may be collocated easily with actuators. The control processor is a 386/25 executing a reduced order model-based algorithm with provision for residual mode filters to compensate for structure interaction. The actuators for the ground demonstration are non-contacting, linear force devices. Results presented illustrate some basic characteristics of control-structure interaction with this hardware. The testbed will be used for evaluation of current technologies and for research in several areas. A brief indication of the evolution of the C-SIDE is given at the conclusion.

Interactional synchrony in chimpanzees: Examination through a finger-tapping experiment.

PubMed

Yu, Lira; Tomonaga, Masaki

2015-05-11

Humans often unconsciously coordinate behaviour with that of others in daily life. This interpersonal coordination, including mimicry and interactional synchrony, has been suggested to play a fundamental role in social interaction. If this coordinative behavior is socially adaptive, it may be shared with other highly social animal species. The current study targeted chimpanzees, which phylogenetically are the closest living relatives of humans and live in complex social groups, and examined whether interactional synchrony would emerge in pairs of chimpanzees when auditory information about a partner's movement was provided. A finger-tapping task was introduced via touch panels to elicit repetitive and rhythmic movement from each chimpanzee. We found that one of four chimpanzees produced significant changes in both tapping tempo and timing of the tapping relative to its partner's tap when auditory sounds were provided. Although the current results may have limitations in generalizing to chimpanzees as a species, we suggest that a finger-tapping task is one potential method to investigate interactional synchrony in chimpanzees under a laboratory setup.

Experience of targeting subsidies on insecticide-treated nets: what do we know and what are the knowledge gaps?

PubMed

Worrall, Eve; Hill, Jenny; Webster, Jayne; Mortimer, Julia

2005-01-01

Widespread coverage of vulnerable populations with insecticide-treated nets (ITNs) constitutes an important component of the Roll Back Malaria (RBM) strategy to control malaria. The Abuja Targets call for 60% coverage of children under 5 years of age and pregnant women by 2005; but current coverage in Africa is unacceptably low. The RBM 'Strategic Framework for Coordinated National Action in Scaling-up Insecticide-Treated Netting Programmes in Africa' promotes coordinated national action and advocates sustained public provision of targeted subsidies to maximise public health benefits, alongside support and stimulation of the private sector. Several countries have already planned or initiated targeted subsidy schemes either on a pilot scale or on a national scale, and have valuable experience which can inform future interventions. The WHO RBM 'Workshop on mapping models for delivering ITNs through targeted subsidies' held in Zambia in 2003 provided an opportunity to share and document these country experiences. This paper brings together experiences presented at the workshop with other information on experiences of targeting subsidies on ITNs, net treatment kits and retreatment services (ITN products) in order to describe alternative approaches, highlight their similarities and differences, outline lessons learnt, and identify gaps in knowledge. We find that while there is a growing body of knowledge on different approaches to targeting ITN subsidies, there are significant gaps in knowledge in crucial areas. Key questions regarding how best to target, how much it will cost and what outcomes (levels of coverage) to expect remain unanswered. High quality, well-funded monitoring and evaluation of alternative approaches to targeting ITN subsidies is vital to develop a knowledge base so that countries can design and implement effective strategies to target ITN subsidies.

Pre-launch simulation experiment of microwave-ionosphere nonlinear interaction rocket experiment in the space plasma chamber

NASA Astrophysics Data System (ADS)

Kaya, N.; Tsutsui, M.; Matsumoto, H.; Kimura, I.

1980-09-01

A pre-flight test experiment of a microwave-ionosphere nonlinear interaction rocket experiment (MINIX) has been carried out in a space plasma simulation chamber. Though the first rocket experiment ended up in failure because of a high voltage trouble, interesting results are observed in the pre-flight experiment. A significant microwave heating of plasma up to 300% temperature increase is observed. Strong excitations of plasma waves by the transmitted microwaves in the VLF and HF range are observed as well. These microwave effects may have to be taken into account in solar power satellite projects in the future.

A study on the application of voice interaction in automotive human machine interface experience design

NASA Astrophysics Data System (ADS)

Huang, Zhaohui; Huang, Xiemin

2018-04-01

This paper, firstly, introduces the application trend of the integration of multi-channel interactions in automotive HMI ((Human Machine Interface) from complex information models faced by existing automotive HMI and describes various interaction modes. By comparing voice interaction and touch screen, gestures and other interaction modes, the potential and feasibility of voice interaction in automotive HMI experience design are concluded. Then, the related theories of voice interaction, identification technologies, human beings' cognitive models of voices and voice design methods are further explored. And the research priority of this paper is proposed, i.e. how to design voice interaction to create more humane task-oriented dialogue scenarios to enhance interactive experiences of automotive HMI. The specific scenarios in driving behaviors suitable for the use of voice interaction are studied and classified, and the usability principles and key elements for automotive HMI voice design are proposed according to the scenario features. Then, through the user participatory usability testing experiment, the dialogue processes of voice interaction in automotive HMI are defined. The logics and grammars in voice interaction are classified according to the experimental results, and the mental models in the interaction processes are analyzed. At last, the voice interaction design method to create the humane task-oriented dialogue scenarios in the driving environment is proposed.

Inter-hemispheric interaction facilitates face processing.

PubMed

Compton, Rebecca J

2002-01-01

Many recent studies have revealed that interaction between the left and right cerebral hemispheres can aid in task performance, but these studies have tended to examine perception of simple stimuli such as letters, digits or simple shapes, which may have limited naturalistic validity. The present study extends these prior findings to a more naturalistic face perception task. Matching tasks required subjects to indicate when a target face matched one of two probe faces. Matches could be either across-field, requiring inter-hemispheric interaction, or within-field, not requiring inter-hemispheric interaction. Subjects indicated when faces matched in emotional expression (Experiment 1; n=32) or in character identity (Experiment 2; n=32). In both experiments, across-field performance was significantly better than within-field performance, supporting the primary hypothesis. Further, this advantage was greater for the more difficult character identity task. Results offer qualified support for the hypothesis that inter-hemispheric interaction is especially advantageous as task demands increase.

Integrating theory into disturbance interaction experiments to better inform ecosystem management.

PubMed

Foster, Claire N; Sato, Chloe F; Lindenmayer, David B; Barton, Philip S

2016-04-01

Managing multiple, interacting disturbances is a key challenge to biodiversity conservation, and one that will only increase as global change drivers continue to alter disturbance regimes. Theoretical studies have highlighted the importance of a mechanistic understanding of stressor interactions for improving the prediction and management of interactive effects. However, many conservation studies are not designed or interpreted in the context of theory and instead focus on case-specific management questions. This is a problem as it means that few studies test the relationships highlighted in theoretical models as being important for ecological management. We explore the extent of this problem among studies of interacting disturbances by reviewing recent experimental studies of the interaction between fire and grazing in terrestrial ecosystems. Interactions between fire and grazing can occur via a number of pathways; one disturbance can modify the other's likelihood, intensity or spatial distribution, or one disturbance can alter the other's impacts on individual organisms. The strength of such interactions will vary depending on disturbance attributes (e.g. size or intensity), and this variation is likely to be nonlinear. We show that few experiments testing fire-grazing interactions are able to identify the mechanistic pathway driving an observed interaction, and most are unable to detect nonlinear effects. We demonstrate how these limitations compromise the ability of experimental studies to effectively inform ecological management. We propose a series of adjustments to the design of disturbance interaction experiments that would enable tests of key theoretical pathways and provide the deeper ecological understanding necessary for effective management. Such considerations are relevant to studies of a broad range of ecological interactions and are critical to informing the management of disturbance regimes in the context of accelerating global change. © 2015 John

Genetic Risk by Experience Interaction for Childhood Internalizing Problems: Converging Evidence across Multiple Methods

ERIC Educational Resources Information Center

Vendlinski, Matthew K.; Lemery-Chalfant, Kathryn; Essex, Marilyn J.; Goldsmith, H. Hill

2011-01-01

Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental…

Plasma block acceleration based upon the interaction between double targets and an ultra-intense linearly polarized laser pulse

NASA Astrophysics Data System (ADS)

Xu, Yanxia; Wang, Jiaxiang; Hora, Heinrich; Qi, Xin; Xing, Yifan; Yang, Lei; Zhu, Wenjun

2018-04-01

A new scheme of plasma block acceleration based upon the interaction between double targets and an ultra-intense linearly polarized laser pulse with intensity I ˜ 1022 W/cm2 is investigated via two-dimensional particle-in-cell simulations. The targets are composed of a pre-target of low-density aluminium plasma and an overdense main-target of hydrogen plasma. Through intensive parameter optimization, we have observed highly efficient plasma block accelerations with a monochromatic proton beam peaked at GeVs. The underlying mechanism is attributed to the enhancement of the charge separation field due to the properly selected pre-target.

Building a Learning Experience: What Do Learners' Online Interaction Data Imply?

ERIC Educational Resources Information Center

Kokoç, Mehmet; Altun, Arif

2016-01-01

It is still under debate whether learners' interaction data within e-learning and/or open learning environments could be considered as reflections of their learning experiences to be effective or not. Therefore, it is meaningful to explore the nature of these interactions and to make meaningful conclusions. This study aims to explore what the…

CrashEd--A Live Immersive, Learning Experience Embedding STEM Subjects in a Realistic, Interactive Crime Scene

ERIC Educational Resources Information Center

Bassford, Marie L.; Crisp, Annette; O'Sullivan, Angela; Bacon, Joanne; Fowler, Mark

2016-01-01

Interactive experiences are rapidly becoming popular via the surge of "escape rooms"; part game and part theatre, the "escape" experience is exploding globally, having gone from zero offered at the outset of 2010 to at least 2800 different experiences available worldwide today. CrashEd is an interactive learning experience that…

The Interactions between the Long Non-coding RNA NERDL and Its Target Gene Affect Wood Formation in Populus tomentosa

PubMed Central

Shi, Wan; Quan, Mingyang; Du, Qingzhang; Zhang, Deqiang

2017-01-01

Long non-coding RNAs (lncRNAs) are important regulatory factors for plant growth and development, but little is known about the allelic interactions of lncRNAs with mRNA in perennial plants. Here, we analyzed the interaction of the NERD (Needed for RDR2-independent DNA methylation) Populus tomentosa gene PtoNERD with its putative regulator, the lncRNA NERDL (NERD-related lncRNA), which partially overlaps with the promoter region of this gene. Expression analysis in eight tissues showed a positive correlation between NERDL and PtoNERD (r = 0.62), suggesting that the interaction of NERDL with its putative target might be involved in wood formation. We conducted association mapping in a natural population of P. tomentosa (435 unrelated individuals) to evaluate genetic variation and the interaction of the lncRNA NERDL with PtoNERD. Using additive and dominant models, we identified 30 SNPs (P < 0.01) associated with five tree growth and wood property traits. Each SNP explained 3.90–8.57% of phenotypic variance, suggesting that NERDL and its putative target play a common role in wood formation. Epistasis analysis uncovered nine SNP-SNP association pairs between NERDL and PtoNERD, with an information gain of -7.55 to 2.16%, reflecting the strong interactions between NERDL and its putative target. This analysis provides a powerful method for deciphering the genetic interactions of lncRNAs with mRNA and dissecting the complex genetic network of quantitative traits in trees. PMID:28674544

miRTar2GO: a novel rule-based model learning method for cell line specific microRNA target prediction that integrates Ago2 CLIP-Seq and validated microRNA-target interaction data.

PubMed

Ahadi, Alireza; Sablok, Gaurav; Hutvagner, Gyorgy

2017-04-07

MicroRNAs (miRNAs) are ∼19-22 nucleotides (nt) long regulatory RNAs that regulate gene expression by recognizing and binding to complementary sequences on mRNAs. The key step in revealing the function of a miRNA, is the identification of miRNA target genes. Recent biochemical advances including PAR-CLIP and HITS-CLIP allow for improved miRNA target predictions and are widely used to validate miRNA targets. Here, we present miRTar2GO, which is a model, trained on the common rules of miRNA-target interactions, Argonaute (Ago) CLIP-Seq data and experimentally validated miRNA target interactions. miRTar2GO is designed to predict miRNA target sites using more relaxed miRNA-target binding characteristics. More importantly, miRTar2GO allows for the prediction of cell-type specific miRNA targets. We have evaluated miRTar2GO against other widely used miRNA target prediction algorithms and demonstrated that miRTar2GO produced significantly higher F1 and G scores. Target predictions, binding specifications, results of the pathway analysis and gene ontology enrichment of miRNA targets are freely available at http://www.mirtar2go.org. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Flyer Target Acceleration and Energy Transfer at its Collision with Massive Targets

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

Borodziuk, S.; Kasperczuk, A.; Pisarczyk, T.

2006-01-15

Numerical modelling was aimed at simulation of successive events resulting from interaction of laser beam-single and double targets. It was performed by means of the 2D Lagrangian hydrodynamics code ATLANT-HE. This code is based on one-fluid and two-temperature model of plasma with electron and ion heat conductivity considerations. The code has an advanced treatment of laser light propagation and absorption. This numerical modelling corresponds to the experiment, which was carried out with the use of the PALS facility. Two types of planar solid targets, i.e. single massive Al slabs and double targets consisting of 6 {mu}m thick Al foil andmore » Al slab were applied. The targets were irradiated by the iodine laser pulses of two wavelengths: 1.315 and 0.438 {mu}m. A pulse duration of 0.4 ns and a focal spot diameter of 250 {mu}m at a laser energy of 130 J were used. The numerical modelling allowed us to obtain a more detailed description of shock wave propagation and crater formation.« less

Maximize, minimize or target - optimization for a fitted response from a designed experiment

DOE PAGES

Anderson-Cook, Christine Michaela; Cao, Yongtao; Lu, Lu

2016-04-01

One of the common goals of running and analyzing a designed experiment is to find a location in the design space that optimizes the response of interest. Depending on the goal of the experiment, we may seek to maximize or minimize the response, or set the process to hit a particular target value. After the designed experiment, a response model is fitted and the optimal settings of the input factors are obtained based on the estimated response model. Furthermore, the suggested optimal settings of the input factors are then used in the production environment.

Glucocorticoid Receptor Interacting Co-regulators: Putative Candidates for Future Drug Targeting Therapy.

PubMed

Di Silvestre, Alessia; Lucafo, Marianna; De Iudicibus, Sara; Ventura, Alessandro; Martelossi, Stefano; Stocco, Gabriele; Decorti, Giuliana

2017-01-01

Glucocorticoids (GCs) are largely used in different inflammatory, autoimmune and proliferative diseases. To date their mechanism of action is not completely clear and more studies are necessary, in particular to explain the great interindividual variability in clinical response. In this panorama the glucocorticoid receptor (GR) has an important role: in fact it regulates the pharmacological response thanks to the capability to interact with different molecules (DNA, RNA, ncRNA and proteins) that are known to influence its activity. In this review our aim is to highlight the knowledge about the role of protein-protein, RNAprotein interactions and epigenetic modifications on the GR and the consequent response to GCs. The characteristics of these interactions with the GR and their effects on the pharmacological activity of GCs will be examined. This information could contribute to the prediction of individual sensitivity to steroids through the identification of new markers of GC resistance. In addition this knowledge may be used in developing new strategies for targeted therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dynamic interaction between vehicles and infrastructure experiment (DIVINE) : policy implications

DOT National Transportation Integrated Search

1998-01-01

The Dynamic Interaction between Vehicles and Infrastructure Experiment (DIVINE) Project provided scientific evidence of the dynamic effects of heavy vehicles and their suspension systems on pavements and bridges. These conclusions are detailed in the...

Dynamic interaction between vehicles and infrastructure experiment (DIVINE) : technical report

DOT National Transportation Integrated Search

1998-10-27

The Dynamic Interaction between Vehicles and Infrastructure Experiment (DIVINE) Project provides scientific evidence of the dynamic effects of heavy vehicles and their suspension systems on pavements and bridges in support of transport policy decisio...

Surface targeting of the dopamine transporter involves discrete epitopes in the distal C terminus but does not require canonical PDZ domain interactions.

PubMed

Bjerggaard, Christian; Fog, Jacob U; Hastrup, Hanne; Madsen, Kenneth; Loland, Claus J; Javitch, Jonathan A; Gether, Ulrik

2004-08-04

The human dopamine transporter (hDAT) contains a C-terminal type 2 PDZ (postsynaptic density 95/Discs large/zona occludens 1) domain-binding motif (LKV) known to interact with PDZ domain proteins such as PICK1 (protein interacting with C-kinase 1). As reported previously, we found that, after deletion of this motif, hDAT was retained in the endoplasmic reticulum (ER) of human embryonic kidney (HEK) 293 and Neuro2A cells, suggesting that PDZ domain interactions might be critical for hDAT targeting. Nonetheless, substitution of LKV with SLL, the type 1 PDZ-binding sequence from the beta2-adrenergic receptor, did not disrupt plasma membrane targeting. Moreover, the addition of an alanine to the hDAT C terminus (+Ala), resulting in an LKVA termination sequence, or substitution of LKV with alanines (3xAla_618-620) prevented neither plasma membrane targeting nor targeting into sprouting neurites of differentiated N2A cells. The inability of +Ala and 3xAla_618-620 to bind PDZ domains was confirmed by lack of colocalization with PICK1 in cotransfected HEK293 cells and by the inability of corresponding C-terminal fusion proteins to pull down purified PICK1. Thus, although residues in the hDAT C terminus are indispensable for proper targeting, PDZ domain interactions are not required. By progressive substitutions with beta2-adrenergic receptor sequence, and by triple-alanine substitutions in the hDAT C terminus, we examined the importance of epitopes preceding the LKV motif. Substitution of RHW(615-617) with alanines caused retention of the transporter in the ER despite preserved ability of this mutant to bind PICK1. We propose dual roles of the hDAT C terminus: a role independent of PDZ interactions for ER export and surface targeting, and a not fully clarified role involving PDZ interactions with proteins such as PICK1.

Penetration experiments in aluminum and Teflon targets of widely variable thickness

NASA Technical Reports Server (NTRS)

Hoerz, F.; Cintala, Mark J.; Bernhard, R. P.; See, T. H.

1994-01-01

The morphologies and detailed dimensions of hypervelocity craters and penetration holes on space-exposed surfaces faithfully reflect the initial impact conditions. However, current understanding of this postmortem evidence and its relation to such first-order parameters as impact velocity or projectile size and mass is incomplete. While considerable progress is being made in the numerical simulation of impact events, continued impact simulations in the laboratory are needed to obtain empirical constraints and insights. This contribution summarizes such experiments with Al and Teflon targets that were carried out in order to provide a better understanding of the crater and penetration holes reported from the Solar Maximum Mission (SMM) and the Long Duration Exposure Facility (LDEF) satellites. A 5-mm light gas gun was used to fire spherical soda-lime glass projectiles from 50 to 3175 microns in diameter (D(sub P)), at a nominal 6 km/s, into Al (1100 series; annealed) and Teflon (Teflon(sup TFE)) targets. Targets ranged in thickness (T) from infinite halfspace targets (T approx. equals cm) to ultrathin foils (T approx. equals micron), yielding up to 3 degrees of magnitude variation in absolute and relative (D(sub P)/T) target thickness. This experimental matrix simulates the wide range in D(sub P)/T experienced by a space-exposed membrane of constant T that is being impacted by projectiles of widely varying sizes.

Rational Design of Multifunctional Gold Nanoparticles via Host-Guest Interaction for Cancer-Targeted Therapy.

PubMed

Chen, Wei-Hai; Lei, Qi; Luo, Guo-Feng; Jia, Hui-Zhen; Hong, Sheng; Liu, Yu-Xin; Cheng, Yin-Jia; Zhang, Xian-Zheng

2015-08-12

A versatile gold nanoparticle-based multifunctional nanocomposite AuNP@CD-AD-DOX/RGD was constructed flexibly via host-guest interaction for targeted cancer chemotherapy. The pH-sensitive anticancer prodrug AD-Hyd-DOX and the cancer-targeted peptide AD-PEG8-GRGDS were modified on the surface of AuNP@CD simultaneously, which endowed the resultant nanocomposite with the capability to selectively eliminate cancer cells. In vitro studies indicated that the AuNP@CD-AD-DOX/RGD nanocomposite was preferentially uptaken by cancer cells via receptor-mediated endocytosis. Subsequently, anticancer drug DOX was released rapidly upon the intracellular trigger of the acid microenvirenment of endo/lysosomes, inducing apoptosis in cancer cells. As the ideal drug nanocarrier, the multifunctional gold nanoparticles with the active targeting and controllable intracellular release ability hold the great potential in cancer therapy.

Discovery & Interaction in Astro 101 Laboratory Experiments

NASA Astrophysics Data System (ADS)

Maloney, Frank Patrick; Maurone, Philip; DeWarf, Laurence E.

2016-01-01

The availability of low-cost, high-performance computing hardware and software has transformed the manner by which astronomical concepts can be re-discovered and explored in a laboratory that accompanies an astronomy course for arts students. We report on a strategy, begun in 1992, for allowing each student to understand fundamental scientific principles by interactively confronting astronomical and physical phenomena, through direct observation and by computer simulation. These experiments have evolved as :a) the quality and speed of the hardware has greatly increasedb) the corresponding hardware costs have decreasedc) the students have become computer and Internet literated) the importance of computationally and scientifically literate arts graduates in the workplace has increased.We present the current suite of laboratory experiments, and describe the nature, procedures, and goals in this two-semester laboratory for liberal arts majors at the Astro 101 university level.

A computer program to determine the possible daily release window for sky target experiments

NASA Technical Reports Server (NTRS)

Michaud, N. H.

1973-01-01

A computer program is presented which is designed to determine the daily release window for sky target experiments. Factors considered in the program include: (1) target illumination by the sun at release time and during the tracking period; (2) look angle elevation above local horizon from each tracking station to the target; (3) solar depression angle from the local horizon of each tracking station during the experimental period after target release; (4) lunar depression angle from the local horizon of each tracking station during the experimental period after target release; and (5) total sky background brightness as seen from each tracking station while viewing the target. Program output is produced in both graphic and data form. Output data can be plotted for a single calendar month or year. The numerical values used to generate the plots are furnished to permit a more detailed review of the computed daily release windows.

Identification of Keratinocyte Growth Factor as a Target of microRNA-155 in Lung Fibroblasts: Implication in Epithelial-Mesenchymal Interactions

PubMed Central

Chevalier, Benoit; Puisségur, Marie-Pierre; Lebrigand, Kevin; Robbe-Sermesant, Karine; Bertero, Thomas; Lino Cardenas, Christian L.; Courcot, Elisabeth; Rios, Géraldine; Fourre, Sandra; Lo-Guidice, Jean-Marc; Marcet, Brice; Cardinaud, Bruno; Barbry, Pascal; Mari, Bernard

2009-01-01

Background Epithelial-mesenchymal interactions are critical in regulating many aspects of vertebrate embryo development, and for the maintenance of homeostatic equilibrium in adult tissues. The interactions between epithelium and mesenchyme are believed to be mediated by paracrine signals such as cytokines and extracellular matrix components secreted from fibroblasts that affect adjacent epithelia. In this study, we sought to identify the repertoire of microRNAs (miRNAs) in normal lung human fibroblasts and their potential regulation by the cytokines TNF-α, IL-1β and TGF-β. Methodology/Principal Findings MiR-155 was significantly induced by inflammatory cytokines TNF-α and IL-1β while it was down-regulated by TGF-β. Ectopic expression of miR-155 in human fibroblasts induced modulation of a large set of genes related to “cell to cell signalling”, “cell morphology” and “cellular movement”. This was consistent with an induction of caspase-3 activity and with an increase in cell migration in fibroblasts tranfected with miR-155. Using different miRNA bioinformatic target prediction tools, we found a specific enrichment for miR-155 predicted targets among the population of down-regulated transcripts. Among fibroblast-selective targets, one interesting hit was keratinocyte growth factor (KGF, FGF-7), a member of the fibroblast growth factor (FGF) family, which owns two potential binding sites for miR-155 in its 3′-UTR. Luciferase assays experimentally validated that miR-155 can efficiently target KGF 3′-UTR. Site-directed mutagenesis revealed that only one out of the 2 potential sites was truly functional. Functional in vitro assays experimentally validated that miR-155 can efficiently target KGF 3′-UTR. Furthermore, in vivo experiments using a mouse model of lung fibrosis showed that miR-155 expression level was correlated with the degree of lung fibrosis. Conclusions/Significance Our results strongly suggest a physiological function of miR-155 in

Selective Attention and Distraction in Context-Interactive Situations in Children and Adults.

ERIC Educational Resources Information Center

Ackerman, Brian P.

1987-01-01

Results from three experiments suggest that attention to context may benefit target recall in situations in which the context can be meaningfully related to the target. Adults seem to be more able to engage in context-interactive processing of stimulus information than are children, who base target selection on perceptual information. (PCB)

A free-jet Hg target operating in a high magnetic field intersecting a high-power proton beam

NASA Astrophysics Data System (ADS)

Graves, Van; Spampinato, Philip; Gabriel, Tony; Kirk, Harold; Simos, Nicholas; Tsang, Thomas; McDonald, Kirk; Peter Titus; Fabich, Adrian; Haseroth, Helmut; Lettry, Jacques

2006-06-01

A proof-of-principal experiment to investigate the interaction of a proton beam, high magnetic field, and high-Z target is planned to take place at CERN in early 2007. This experiment is part of the Muon Collider Collaboration, with participants from Brookhaven National Laboratory, Princeton University, Massachusetts Institute Of Technology, European Organization for Nuclear Research-CERN, Rutherford Appleton Laboratory, and Oak Ridge National Laboratory. An unconstrained mercury jet target system that interacts with a high power (1 MW) proton beam in a high magnetic field (15 T) is being designed. The Hg jet diameter is 1-cm with a velocity up to 20 m/s. A laser optical diagnostic system will be incorporated into the target design to permit observation of the dispersal of the jet resulting from interaction with a 24 GeV proton beam with up to 20×1012 ppp. The target system includes instruments for sensing mercury vapor, temperature, flow rate, and sump tank level, and the means to position the jet relative to the magnetic axis of a solenoid and the proton beam. The design considerations for the system include all issues dealing with safely handling approximately 23 l of Hg, transporting the target system and the mercury to CERN, decommissioning the experiment, and returning the mildly activated equipment and Hg to the US.

A free-jet Hg target operating in a high magnetic field intersecting a high-power proton beam

NASA Astrophysics Data System (ADS)

Van Graves; Spampinato, Philip; Gabriel, Tony; Kirk, Harold; Simos, Nicholas; Tsang, Thomas; McDonald, Kirk; Peter Titus; Fabich, Adrian; Haseroth, Helmut; Lettry, Jacques

2006-06-01

A proof-of-principal experiment to investigate the interaction of a proton beam, high magnetic field, and high- Z target is planned to take place at CERN in early 2007. This experiment is part of the Muon Collider Collaboration, with participants from Brookhaven National Laboratory, Princeton University, Massachusetts Institute Of Technology, European Organization for Nuclear Research-CERN, Rutherford Appleton Laboratory, and Oak Ridge National Laboratory. An unconstrained mercury jet target system that interacts with a high power (1 MW) proton beam in a high magnetic field (15 T) is being designed. The Hg jet diameter is 1-cm with a velocity up to 20 m/s. A laser optical diagnostic system will be incorporated into the target design to permit observation of the dispersal of the jet resulting from interaction with a 24 GeV proton beam with up to 20×10 12 ppp. The target system includes instruments for sensing mercury vapor, temperature, flow rate, and sump tank level, and the means to position the jet relative to the magnetic axis of a solenoid and the proton beam. The design considerations for the system include all issues dealing with safely handling approximately 23 l of Hg, transporting the target system and the mercury to CERN, decommissioning the experiment, and returning the mildly activated equipment and Hg to the US.

Looking for polarization bremsstrahlung in the midst of inner-shell ionization: Analysis of the x-ray spectrum in electron interactions with thin-film targets

NASA Astrophysics Data System (ADS)

Quarles, C. A.; Portillo, S.

1999-06-01

Calculations of the total bremsstrahlung spectrum including polarization bremsstrahlung (PB) for high energy electrons on atoms have been made recently by A. V. Korol, A. G. Lyalin and A. V. Solovy'ov. This has motivated us to look for the PB effect for 25 and 50 keV electrons on a variety of thin-film targets including C, Al, Cu, Ag, Tb and Au. PB is predicted to be a significant increase in radiated photon intensity at energies below the target K and L absorption edges. A good model of the thick-target bremsstrahlung background due to electrons elastically scattered into the detector window and a good understanding of the Ge and Si(Li) detector response are crucial for interpretation of the data. We have used a geometry in which the detector-window background is significantly reduced from that in prior experiments. We have analyzed the photon spectra from above 4 keV to the kinematic endpoint. The data are very well fit by normal bremsstrahlung alone. No PB contribution is seen in the data. Finally, we conclude with an argument why, in fact, we should not expect any PB effect when charged particles interact with solid film targets.

Identification of Histone Deacetylase (HDAC) as a drug target against MRSA via interolog method of protein-protein interaction prediction.

PubMed

Uddin, Reaz; Tariq, Syeda Sumayya; Azam, Syed Sikander; Wadood, Abdul; Moin, Syed Tarique

2017-08-30

Patently, Protein-Protein Interactions (PPIs) lie at the core of significant biological functions and make the foundation of host-pathogen relationships. Hence, the current study is aimed to use computational biology techniques to predict host-pathogen Protein-Protein Interactions (HP-PPIs) between MRSA and Humans as potential drug targets ultimately proposing new possible inhibitors against them. As a matter of fact this study is based on the Interolog method which implies that homologous proteins retain their ability to interact. A distant homolog approach based on Interolog method was employed to speculate MRSA protein homologs in Humans using PSI-BLAST. In addition the protein interaction partners of these homologs as listed in Database of Interacting Proteins (DIP) were predicted to interact with MRSA as well. Moreover, a direct approach using BLAST was also applied so as to attain further confidence in the strategy. Consequently, the common HP-PPIs predicted by both approaches are suggested as potential drug targets (22%) whereas, the unique HP-PPIs estimated only through distant homolog approach are presented as novel drug targets (12%). Furthermore, the most repeated entry in our results was found to be MRSA Histone Deacetylase (HDAC) which was then modeled using SWISS-MODEL. Eventually, small molecules from ZINC, selected randomly, were docked against HDAC using Auto Dock and are suggested as potential binders (inhibitors) based on their energetic profiles. Thus the current study provides basis for further in-depth analysis of such data which not only include MRSA but other deadly pathogens as well. Copyright © 2017 Elsevier B.V. All rights reserved.

Using Data Independent Acquisition (DIA) to Model High-responding Peptides for Targeted Proteomics Experiments*

PubMed Central

Searle, Brian C.; Egertson, Jarrett D.; Bollinger, James G.; Stergachis, Andrew B.; MacCoss, Michael J.

2015-01-01

Targeted mass spectrometry is an essential tool for detecting quantitative changes in low abundant proteins throughout the proteome. Although selected reaction monitoring (SRM) is the preferred method for quantifying peptides in complex samples, the process of designing SRM assays is laborious. Peptides have widely varying signal responses dictated by sequence-specific physiochemical properties; one major challenge is in selecting representative peptides to target as a proxy for protein abundance. Here we present PREGO, a software tool that predicts high-responding peptides for SRM experiments. PREGO predicts peptide responses with an artificial neural network trained using 11 minimally redundant, maximally relevant properties. Crucial to its success, PREGO is trained using fragment ion intensities of equimolar synthetic peptides extracted from data independent acquisition experiments. Because of similarities in instrumentation and the nature of data collection, relative peptide responses from data independent acquisition experiments are a suitable substitute for SRM experiments because they both make quantitative measurements from integrated fragment ion chromatograms. Using an SRM experiment containing 12,973 peptides from 724 synthetic proteins, PREGO exhibits a 40–85% improvement over previously published approaches at selecting high-responding peptides. These results also represent a dramatic improvement over the rules-based peptide selection approaches commonly used in the literature. PMID:26100116

The polarized atomic-beam target for the EDDA experiment and the time-reversal invariance test at COSY

NASA Astrophysics Data System (ADS)

Eversheim, P. D.; Altmeier, M.; Felden, O.

1997-02-01

For the the EDDA experiment, which was set up to measure the p¯-p¯ excitation function during the acceleration ramp of the cooler synchrotron COSY at Jülich, a polarized atomic-beam target was designed regarding the restrictions imposed by the geometry of the EDDA detector. Later, when the time-reversal invariance experiment is to be performed, the EDDA detector will serve as efficient internal polarimeter and the source has to deliver tensor polarized deuterons. The modular design of this polarized atomic-beam target that allows to meet these conditions will be discussed in comparison to other existing polarized atomic-beam targets.

Target-specific NMR detection of protein-ligand interactions with antibody-relayed 15N-group selective STD.

PubMed

Hetényi, Anasztázia; Hegedűs, Zsófia; Fajka-Boja, Roberta; Monostori, Éva; Kövér, Katalin E; Martinek, Tamás A

2016-12-01

Fragment-based drug design has been successfully applied to challenging targets where the detection of the weak protein-ligand interactions is a key element. 1 H saturation transfer difference (STD) NMR spectroscopy is a powerful technique for this work but it requires pure homogeneous proteins as targets. Monoclonal antibody (mAb)-relayed 15 N-GS STD spectroscopy has been developed to resolve the problem of protein mixtures and impure proteins. A 15 N-labelled target-specific mAb is selectively irradiated and the saturation is relayed through the target to the ligand. Tests on the anti-Gal-1 mAb/Gal-1/lactose system showed that the approach is experimentally feasible in a reasonable time frame. This method allows detection and identification of binding molecules directly from a protein mixture in a multicomponent system.

Segmented beryllium target for a 2 MW super beam facility

DOE PAGES

Davenne, T.; Caretta, O.; Densham, C.; ...

2015-09-14

The Long Baseline Neutrino Facility (LBNF, formerly the Long Baseline Neutrino Experiment) is under design as a next generation neutrino oscillation experiment, with primary objectives to search for CP violation in the leptonic sector, to determine the neutrino mass hierarchy and to provide a precise measurement of θ 23. The facility will generate a neutrino beam at Fermilab by the interaction of a proton beam with a target material. At the ultimate anticipated proton beam power of 2.3 MW the target material must dissipate a heat load of between 10 and 25 kW depending on the target size. This paper presents amore » target concept based on an array of spheres and compares it to a cylindrical monolithic target such as that which currently operates at the T2K facility. Thus simulation results show that the proposed technology offers efficient cooling and lower stresses whilst delivering a neutrino production comparable with that of a conventional solid cylindrical target.« less

A T0/Trigger detector for the External Target Experiment at CSR

NASA Astrophysics Data System (ADS)

Hu, D.; Shao, M.; Sun, Y.; Li, C.; Chen, H.; Tang, Z.; Zhang, Y.; Zhou, J.; Zeng, H.; Zhao, X.; You, W.; Song, G.; Deng, P.; Lu, J.; Zhao, L.

2017-06-01

A new T0/Trigger detector based on multi-gap resistive plate chamber (MRPC) technology has been constructed and tested for the external target experiment (ETE) at HIRFL-CSR. It measures the multiplicity and timing information of particles produced in heavy-ion collisions at the target region, providing necessary event collision time (T0) and collision centrality with high precision. Monte-Carlo simulation shows a time resolution of several tens of picosecond can be achieved at central collisions. The experimental tests have been performed for this prototype detector at the CSR-ETE. The preliminary results are shown to demonstrate the performance of the T0/Trigger detector.

The Dynamic Reactance Interaction - How Vested Interests Affect People's Experience, Behavior, and Cognition in Social Interactions.

PubMed

Steindl, Christina; Jonas, Eva

2015-01-01

In social interactions, individuals may sometimes pursue their own interests at the expense of their interaction partner. Such self-interested behaviors impose a threat to the interaction partner's freedom to act. The current article investigates this threat in the context of interdependence and reactance theory. We explore how vested interests influence reactance process stages of an advisor-client interaction. We aim to explore the interactional process that evolves. In two studies, participants took the perspective of a doctor (advisor) or a patient (client). In both studies we incorporated a vested interest. In Study 1 (N = 82) we found that in response to a vested interest of their interaction partner, patients indicated a stronger experience of reactance, more aggressive behavioral intentions, and more biased cognitions than doctors. A serial multiple mediation revealed that a vested interest engendered mistrust toward the interaction partner and this mistrust led to an emerging reactance process. Study 2 (N = 207) further demonstrated that doctors expressed their reactance in a subtle way: they revealed a classic confirmation bias when searching for additional information on their preliminary decision preference, indicating stronger defense motivation. We discuss how these findings can help us to understand how social interactions develop dynamically.

Efficient Parvovirus Replication Requires CRL4Cdt2-Targeted Depletion of p21 to Prevent Its Inhibitory Interaction with PCNA

PubMed Central

Pintel, David J.

2014-01-01

Infection by the autonomous parvovirus minute virus of mice (MVM) induces a vigorous DNA damage response in host cells which it utilizes for its efficient replication. Although p53 remains activated, p21 protein levels remain low throughout the course of infection. We show here that efficient MVM replication required the targeting for degradation of p21 during this time by the CRL4Cdt2 E3-ubiquitin ligase which became re-localized to MVM replication centers. PCNA provides a molecular platform for substrate recognition by the CRL4Cdt2 E3-ubiquitin ligase and p21 targeting during MVM infection required its interaction both with Cdt2 and PCNA. PCNA is also an important co-factor for MVM replication which can be antagonized by p21 in vitro. Expression of a stable p21 mutant that retained interaction with PCNA inhibited MVM replication, while a stable p21 mutant which lacked this interaction did not. Thus, while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers, efficient viral replication required subsequent depletion of p21 to abrogate its inhibition of PCNA. PMID:24699724

Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction with PCNA.

PubMed

Adeyemi, Richard O; Fuller, Matthew S; Pintel, David J

2014-04-01

Infection by the autonomous parvovirus minute virus of mice (MVM) induces a vigorous DNA damage response in host cells which it utilizes for its efficient replication. Although p53 remains activated, p21 protein levels remain low throughout the course of infection. We show here that efficient MVM replication required the targeting for degradation of p21 during this time by the CRL4Cdt2 E3-ubiquitin ligase which became re-localized to MVM replication centers. PCNA provides a molecular platform for substrate recognition by the CRL4Cdt2 E3-ubiquitin ligase and p21 targeting during MVM infection required its interaction both with Cdt2 and PCNA. PCNA is also an important co-factor for MVM replication which can be antagonized by p21 in vitro. Expression of a stable p21 mutant that retained interaction with PCNA inhibited MVM replication, while a stable p21 mutant which lacked this interaction did not. Thus, while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers, efficient viral replication required subsequent depletion of p21 to abrogate its inhibition of PCNA.

Direct Interaction between the WD40 Repeat Protein WDR-23 and SKN-1/Nrf Inhibits Binding to Target DNA

PubMed Central

Leung, Chi K.; Hasegawa, Koichi; Wang, Ying; Deonarine, Andrew; Tang, Lanlan; Miwa, Johji

2014-01-01

SKN-1/Nrf transcription factors activate cytoprotective genes in response to reactive small molecules and strongly influence stress resistance, longevity, and development. The molecular mechanisms of SKN-1/Nrf regulation are poorly defined. We previously identified the WD40 repeat protein WDR-23 as a repressor of Caenorhabditis elegans SKN-1 that functions with a ubiquitin ligase to presumably target the factor for degradation. However, SKN-1 activity and nuclear accumulation are not always correlated, suggesting that there could be additional regulatory mechanisms. Here, we integrate forward genetics and biochemistry to gain insights into how WDR-23 interacts with and regulates SKN-1. We provide evidence that WDR-23 preferentially regulates one of three SKN-1 variants through a direct interaction that is required for normal stress resistance and development. Homology modeling predicts that WDR-23 folds into a β-propeller, and we identify the top of this structure and four motifs at the termini of SKN-1c as essential for the interaction. Two of these SKN-1 motifs are highly conserved in human Nrf1 and Nrf2 and two directly interact with target DNA. Lastly, we demonstrate that WDR-23 can block the ability of SKN-1c to interact with DNA sequences of target promoters identifying a new mechanism of regulation that is independent of the ubiquitin proteasome system, which can become occupied with damaged proteins during stress. PMID:24912676

Manufacturing of calcium, lithium and molybdenum targets for use in nuclear physics experiments

NASA Astrophysics Data System (ADS)

Kheswa, N. Y.; Papka, P.; Buthelezi, E. Z.; Lieder, R. M.; Neveling, R.; Newman, R. T.

2010-02-01

This paper describes methods used in the manufacturing of chemically reactive targets such as calcium ( natCa), lithium-6 ( 6Li) and molybdenum-97 ( 97Mo) for nuclear physics experiments at the iThemba LABS cyclotron facility (Faure, South Africa). Due to the chemical properties of these materials a suitable and controlled environment was established in order to minimize oxygen contamination of targets. Calcium was prepared by means of vacuum evaporation while lithium was cold rolled to a desired thickness. In the case of molybdenum, the metallic powder was melted under vacuum using an e-gun followed by cold rolling of the metal bead to a desired thickness. In addition, latest developments toward the establishment of a dedicated nuclear physics target laboratory are discussed.

Interactivity in Distance Education: The National Open University of Nigeria (NOUN) Experience

ERIC Educational Resources Information Center

Ambe-Uva, Terhemba Nom

2006-01-01

The paper represents a study of students' experience of interactivity in distance education programmes at the National Open University of Nigeria (NOUN). Through surveys and focus groups with students, facilitators, and administrative support staff, we found out that interactivity is a key determinant of student success rate. Majority of the…

Interactive food and beverage marketing: targeting adolescents in the digital age.

PubMed

Montgomery, Kathryn C; Chester, Jeff

2009-09-01

Because of their avid use of new media and their increased spending power, adolescents have become primary targets of a new "Media and Marketing Ecosystem." Digital media resonate particularly well with many of the fundamental developmental tasks of adolescence by enabling instantaneous and constant contact with peers, providing opportunities for self-expression, identity exploration, and social interaction, and facilitating mobility and independence. Six key features of interactive media--ubiquitous connectivity, personalization, peer-to-peer networking, engagement, immersion, and content creation--are emblematic of the ways in which young people are both shaping and being shaped by this new digital culture. The advertising industry, in many instances led by food and beverage marketers, is purposefully exploiting the special relationship that teenagers have with new media, with online marketing campaigns that create unprecedented intimacies between adolescents and the brands and products that now literally surround them. Major food and beverage companies, including Coca-Cola, McDonald's, Burger King, and Kentucky Fried Chicken (KFC), have incorporated these elements into their interactive marketing strategies, posing particular risks to adolescents, who are not being addressed in the current U.S. policy and self-regulatory regimens. However, recent and emerging neuroscience and psychological research on adolescents suggests a need to revisit the traditional approach to regulation of advertising. Despite the growth of interactive marketing, academic research on the impact of digital advertising on children and youth remains underdeveloped. Additional research and policy initiatives are needed to address the growing health threat facing youth in the digital marketplace.

ANITA (Advanced Network for Isotope and TArget laboratories) - The urgent need for a European target preparation network

NASA Astrophysics Data System (ADS)

Schumann, Dorothea; Sibbens, Goedele; Stolarz, Anna; Eberhardt, Klaus; Lommel, Bettina; Stodel, Christelle

2018-05-01

A wide number of research fields in the nuclear sector requires high-quality and well-characterized samples and targets. Currently, only a few laboratories own or have access to the equipment allowing fulfilling such demands. Coordination of activities and sharing resources is therefore mandatory to meet the increasing needs. This very urgent issue has now been addressed by six European target laboratories with an initiative called ANITA (Advanced Network for Isotope and TArget laboratories). The global aim of ANITA is to establish an overarching research infrastructure service for isotope and target production and develop a tight cooperation between the target laboratories in Europe in order to transfer the knowledge and improve the production techniques of well-characterized samples and targets. Moreover, the interaction of the target producers with the users shall be encouraged and intensified to deliver tailor-made targets best-suited to the envisaged experiments. For the realization of this ambitious goal, efforts within the European Commission and strong support by the target-using communities will be necessary. In particular, an appropriate funding instrument has to be found and applied, enabling ANITA to develop from an initiative employed by the interested parties to a real coordination platform.

Physics perspectives with AFTER@LHC (A Fixed Target ExpeRiment at LHC)

NASA Astrophysics Data System (ADS)

Massacrier, L.; Anselmino, M.; Arnaldi, R.; Brodsky, S. J.; Chambert, V.; Da Silva, C.; Didelez, J. P.; Echevarria, M. G.; Ferreiro, E. G.; Fleuret, F.; Gao, Y.; Genolini, B.; Hadjidakis, C.; Hřivnáčová, I.; Kikola, D.; Klein, A.; Kurepin, A.; Kusina, A.; Lansberg, J. P.; Lorcé, C.; Lyonnet, F.; Martinez, G.; Nass, A.; Pisano, C.; Robbe, P.; Schienbein, I.; Schlegel, M.; Scomparin, E.; Seixas, J.; Shao, H. S.; Signori, A.; Steffens, E.; Szymanowski, L.; Topilskaya, N.; Trzeciak, B.; Uggerhøj, U. I.; Uras, A.; Ulrich, R.; Wagner, J.; Yamanaka, N.; Yang, Z.

2018-02-01

AFTER@LHC is an ambitious fixed-target project in order to address open questions in the domain of proton and neutron spins, Quark Gluon Plasma and high-x physics, at the highest energy ever reached in the fixed-target mode. Indeed, thanks to the highly energetic 7 TeV proton and 2.76 A.TeV lead LHC beams, center-of-mass energies as large as = 115 GeV in pp/pA and = 72 GeV in AA can be reached, corresponding to an uncharted energy domain between SPS and RHIC. We report two main ways of performing fixed-target collisions at the LHC, both allowing for the usage of one of the existing LHC experiments. In these proceedings, after discussing the projected luminosities considered for one year of data taking at the LHC, we will present a selection of projections for light and heavy-flavour production.

Prediction of Drug-Target Interaction Networks from the Integration of Protein Sequences and Drug Chemical Structures.

PubMed

Meng, Fan-Rong; You, Zhu-Hong; Chen, Xing; Zhou, Yong; An, Ji-Yong

2017-07-05

Knowledge of drug-target interaction (DTI) plays an important role in discovering new drug candidates. Unfortunately, there are unavoidable shortcomings; including the time-consuming and expensive nature of the experimental method to predict DTI. Therefore, it motivates us to develop an effective computational method to predict DTI based on protein sequence. In the paper, we proposed a novel computational approach based on protein sequence, namely PDTPS (Predicting Drug Targets with Protein Sequence) to predict DTI. The PDTPS method combines Bi-gram probabilities (BIGP), Position Specific Scoring Matrix (PSSM), and Principal Component Analysis (PCA) with Relevance Vector Machine (RVM). In order to evaluate the prediction capacity of the PDTPS, the experiment was carried out on enzyme, ion channel, GPCR, and nuclear receptor datasets by using five-fold cross-validation tests. The proposed PDTPS method achieved average accuracy of 97.73%, 93.12%, 86.78%, and 87.78% on enzyme, ion channel, GPCR and nuclear receptor datasets, respectively. The experimental results showed that our method has good prediction performance. Furthermore, in order to further evaluate the prediction performance of the proposed PDTPS method, we compared it with the state-of-the-art support vector machine (SVM) classifier on enzyme and ion channel datasets, and other exiting methods on four datasets. The promising comparison results further demonstrate that the efficiency and robust of the proposed PDTPS method. This makes it a useful tool and suitable for predicting DTI, as well as other bioinformatics tasks.

Interaction of cellular proteins with BCL-xL targeted to cytoplasmic inclusion bodies in adenovirus infected cells.

PubMed

Subramanian, T; Vijayalingam, S; Kuppuswamy, M; Chinnadurai, G

2015-09-01

Adenovirus-mediated apoptosis was suppressed when cellular anti-apoptosis proteins (BCL-2 and BCL-xL) were substituted for the viral E1B-19K. For unbiased proteomic analysis of proteins targeted by BCL-xL in adenovirus-infected cells and to visualize the interactions with target proteins, BCL-xL was targeted to cytosolic inclusion bodies utilizing the orthoreovirus µNS protein sequences. The chimeric protein was localized in non-canonical cytosolic factory-like sites and promoted survival of virus-infected cells. The BCL-xL-associated proteins were isolated from the cytosolic inclusion bodies in adenovirus-infected cells and analyzed by LC-MS. These proteins included BAX, BAK, BID, BIK and BIM as well as mitochondrial proteins such as prohibitin 2, ATP synthase and DNA-PKcs. Our studies suggested that in addition to the interaction with various pro-apoptotic proteins, the association with certain mitochondrial proteins such as DNA-PKcs and prohibitins might augment the survival function of BCL-xL in virus infected cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Electromagnetic pulse (EMP) radiation by laser interaction with a solid H2 ribbon

NASA Astrophysics Data System (ADS)

De Marco, M.; Krása, J.; Cikhardt, J.; Velyhan, A.; Pfeifer, M.; Dudžák, R.; Dostál, J.; Krouský, E.; Limpouch, J.; Pisarczyk, T.; Kalinowska, Z.; Chodukowski, T.; Ullschmied, J.; Giuffrida, L.; Chatain, D.; Perin, J.-P.; Margarone, D.

2017-08-01

The electromagnetic pulses (EMPs) generated during the interaction of a focused 1.315-μm sub-nanosecond laser pulse with a solid hydrogen ribbon were measured. The strength and temporal characteristics of EMPs were found to be dependent on the target density. If a low density target is ionized during the interaction with the laser, and the plasma does not physically touch the target holder, the EMP is weaker in strength and shorter in time duration. It is shown that during the H2 target experiment, the EMP does not strongly affect the response of fast electronic devices. The measurements of the EMP were carried out by Rohde&Schwarz B-Probes, particularly sensitive in the frequency range from 30 MHz and 1 GHz. Numerical simulations of resonant frequencies of the target chamber used in the experiment at the Prague Asterix Laser System kJ-class laser facility elucidate the peaked structure of EMP frequency spectra in the GHz domain.

Single-particle fusion of influenza viruses reveals complex interactions with target membranes

NASA Astrophysics Data System (ADS)

van der Borg, Guus; Braddock, Scarlett; Blijleven, Jelle S.; van Oijen, Antoine M.; Roos, Wouter H.

2018-05-01

The first step in infection of influenza A virus is contact with the host cell membrane, with which it later fuses. The composition of the target bilayer exerts a complex influence on both fusion efficiency and time. Here, an in vitro, single-particle approach is used to study this effect. Using total internal reflection fluorescence (TIRF) microscopy and a microfluidic flow cell, the hemifusion of single virions is visualized. Hemifusion efficiency and kinetics are studied while altering target bilayer cholesterol content and sialic-acid donor. Cholesterol ratios tested were 0%, 10%, 20%, and 40%. Sialic-acid donors GD1a and GYPA were used. Both cholesterol ratio and sialic-acid donors proved to have a significant effect on hemifusion efficiency. Furthermore, comparison between GD1a and GYPA conditions shows that the cholesterol dependence of the hemifusion time is severely affected by the sialic-acid donor. Only GD1a shows a clear increasing trend in hemifusion efficiency and time with increasing cholesterol concentration of the target bilayer with maximum rates for GD1A and 40% cholesterol. Overall our results show that sialic acid donor and target bilayer composition should be carefully chosen, depending on the desired hemifusion time and efficiency in the experiment.

Electromagnetic Pulses Generated From Laser Target Interactions at Shenguang II Laser Facility

NASA Astrophysics Data System (ADS)

Yang, Jinwen; Li, Tingshuai; Yi, Tao; Wang, Chuanke; Yang, Ming; Yang, Weiming; Liu, Shenye; Jiang, Shaoen; Ding, Yongkun

2016-10-01

Significant electromagnetic pulses (EMP) can be generated by the intensive laser irradiating solid targets in inertial confinement fusion (ICF). To evaluate the EMP intensity and distribution in and outside the laser chamber, we designed and fabricated a discone antenna with ultra-wide bands of over 10 GHz. The return loss (S11 parameter) of this antenna was below -10 dB and could even achieve under -30 dB at 3.1 GHz. The EMP intensity in this study at 80 cm and 40 cm away from the target chamber center (TCC) reached 400 kV/m and 2000 kV/m. The current results are expected to offer preliminary information to study physics regarding laser plasma interactions and will also lay experimental foundation for EMI shielding design to protect various diagnostics. supported by the Fundamental Research Funds for the Central Universities of China (No. ZYGX2015J108) and National Natural Science Foundation of China (Nos. 11575166 and 51581140)

Interactions between the R2R3-MYB Transcription Factor, AtMYB61, and Target DNA Binding Sites

PubMed Central

Prouse, Michael B.; Campbell, Malcolm M.

2013-01-01

Despite the prominent roles played by R2R3-MYB transcription factors in the regulation of plant gene expression, little is known about the details of how these proteins interact with their DNA targets. For example, while Arabidopsis thaliana R2R3-MYB protein AtMYB61 is known to alter transcript abundance of a specific set of target genes, little is known about the specific DNA sequences to which AtMYB61 binds. To address this gap in knowledge, DNA sequences bound by AtMYB61 were identified using cyclic amplification and selection of targets (CASTing). The DNA targets identified using this approach corresponded to AC elements, sequences enriched in adenosine and cytosine nucleotides. The preferred target sequence that bound with the greatest affinity to AtMYB61 recombinant protein was ACCTAC, the AC-I element. Mutational analyses based on the AC-I element showed that ACC nucleotides in the AC-I element served as the core recognition motif, critical for AtMYB61 binding. Molecular modelling predicted interactions between AtMYB61 amino acid residues and corresponding nucleotides in the DNA targets. The affinity between AtMYB61 and specific target DNA sequences did not correlate with AtMYB61-driven transcriptional activation with each of the target sequences. CASTing-selected motifs were found in the regulatory regions of genes previously shown to be regulated by AtMYB61. Taken together, these findings are consistent with the hypothesis that AtMYB61 regulates transcription from specific cis-acting AC elements in vivo. The results shed light on the specifics of DNA binding by an important family of plant-specific transcriptional regulators. PMID:23741471

Thin liquid sheet target capabilities for ultra-intense laser acceleration of ions at a kHz repetition rate

NASA Astrophysics Data System (ADS)

Klim, Adam; Morrison, J. T.; Orban, C.; Feister, S.; Ngirmang, G. K.; Smith, J.; Frische, K.; Peterson, A. C.; Chowdhury, E. A.; Freeman, R. R.; Roquemore, W. M.

2016-10-01

The success of laser-accelerated ion experiments depends crucially on a number of factors including how thin the targets can be created. We present experimental results demonstrating extremely thin (under 200 nm) water sheet targets that can be used for ultra-intense laser-accelerated ion experiments conducted at the Air Force Research Laboratory at Wright-Patterson Air Force Base. Importantly, these experiments operate at a kHz repetition rate and the recovery time of the liquid targets is fast enough to allow the laser to interact with a refreshed, thin target on every shot. We present results from liquid water targets which are useful for proton acceleration experiments via the mechanism of Target Normal Sheath Acceleration (TNSA). In future work, we will create thin sheets from deuterated water in order to perform laser-accelerated deuteron experiments. This research was sponsored by the Quantum and Non-Equilibrium Processes Division of the AFOSR, under the management of Dr. Enrique Parra, and support from the DOD HPCMP Internship Program.

Polar-direct-drive experiments with contoured-shell targets on OMEGA

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

Marshall, F. J.; Radha, P. B.; Bonino, M. J.

Polar-driven direct-drive experiments recently performed on the OMEGA Laser System have demonstrated the efficacy of using a target with a contoured shell with varying thickness to improve the symmetry and fusion performance of the implosion. The polar-driven contoured-shell implosions have substantially reduced low mode perturbations compared to polar-driven spherical-shell implosions as diagnosed by x-ray radiographs up to shell stagnation. As a result, fusion yields were increased by more than a factor of ~2 without increasing the energy of the laser by the use of contoured shells.

Polar-direct-drive experiments with contoured-shell targets on OMEGA

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

Marshall, F. J.; Radha, P. B.; Bonino, M. J.

Polar-driven direct-drive experiments recently performed on the OMEGA Laser System have demonstrated the efficacy of using a target with a contoured shell with varying thickness to improve the symmetry and fusion performance of the implosion. The polar-driven contoured-shell implosions have substantially reduced low mode perturbations compared to polar-driven spherical-shell implosions as diagnosed by x-ray radiographs up to shell stagnation. Fusion yields were increased by more than a factor of ∼2 without increasing the energy of the laser by the use of contoured shells.

Polar-direct-drive experiments with contoured-shell targets on OMEGA

DOE PAGES

Marshall, F. J.; Radha, P. B.; Bonino, M. J.; ...

2016-01-28

Polar-driven direct-drive experiments recently performed on the OMEGA Laser System have demonstrated the efficacy of using a target with a contoured shell with varying thickness to improve the symmetry and fusion performance of the implosion. The polar-driven contoured-shell implosions have substantially reduced low mode perturbations compared to polar-driven spherical-shell implosions as diagnosed by x-ray radiographs up to shell stagnation. As a result, fusion yields were increased by more than a factor of ~2 without increasing the energy of the laser by the use of contoured shells.

Evaluation for the design of experience in virtual environments: modeling breakdown of interaction and illusion.

PubMed

Marsh, T; Wright, P; Smith, S

2001-04-01

New and emerging media technologies have the potential to induce a variety of experiences in users. In this paper, it is argued that the inducement of experience presupposes that users are absorbed in the illusion created by these media. Looking to another successful visual medium, film, this paper borrows from the techniques used in "shaping experience" to hold spectators' attention in the illusion of film, and identifies what breaks the illusion/experience for spectators. This paper focuses on one medium, virtual reality (VR), and advocates a transparent or "invisible style" of interaction. We argue that transparency keeps users in the "flow" of their activities and consequently enhances experience in users. Breakdown in activities breaks the experience and subsequently provides opportunities to identify and analyze potential causes of usability problems. Adopting activity theory, we devise a model of interaction with VR--through consciousness and activity--and introduce the concept of breakdown in illusion. From this, a model of effective interaction with VR is devised and the occurrence of breakdown in interaction and illusion is identified along a continuum of engagement. Evaluation guidelines for the design of experience are proposed and applied to usability problems detected in an empirical study of a head-mounted display (HMD) VR system. This study shows that the guidelines are effective in the evaluation of VR. Finally, we look at the potential experiences that may be induced in users and propose a way to evaluate user experience in virtual environments (VEs) and other new and emerging media.

Time-compressed spoken word primes crossmodally enhance processing of semantically congruent visual targets.

PubMed

Mahr, Angela; Wentura, Dirk

2014-02-01

Findings from three experiments support the conclusion that auditory primes facilitate the processing of related targets. In Experiments 1 and 2, we employed a crossmodal Stroop color identification task with auditory color words (as primes) and visual color patches (as targets). Responses were faster for congruent priming, in comparison to neutral or incongruent priming. This effect also emerged for different levels of time compression of the auditory primes (to 30 % and 10 % of the original length; i.e., 120 and 40 ms) and turned out to be even more pronounced under high-perceptual-load conditions (Exps. 1 and 2). In Experiment 3, target-present or -absent decisions for brief target displays had to be made, thereby ruling out response-priming processes as a cause of the congruency effects. Nevertheless, target detection (d') was increased by congruent primes (30 % compression) in comparison to incongruent or neutral primes. Our results suggest semantic object-based auditory-visual interactions, which rapidly increase the denoted target object's salience. This would apply, in particular, to complex visual scenes.

Improved prediction of drug-target interactions using regularized least squares integrating with kernel fusion technique.

PubMed

Hao, Ming; Wang, Yanli; Bryant, Stephen H

2016-02-25

Identification of drug-target interactions (DTI) is a central task in drug discovery processes. In this work, a simple but effective regularized least squares integrating with nonlinear kernel fusion (RLS-KF) algorithm is proposed to perform DTI predictions. Using benchmark DTI datasets, our proposed algorithm achieves the state-of-the-art results with area under precision-recall curve (AUPR) of 0.915, 0.925, 0.853 and 0.909 for enzymes, ion channels (IC), G protein-coupled receptors (GPCR) and nuclear receptors (NR) based on 10 fold cross-validation. The performance can further be improved by using a recalculated kernel matrix, especially for the small set of nuclear receptors with AUPR of 0.945. Importantly, most of the top ranked interaction predictions can be validated by experimental data reported in the literature, bioassay results in the PubChem BioAssay database, as well as other previous studies. Our analysis suggests that the proposed RLS-KF is helpful for studying DTI, drug repositioning as well as polypharmacology, and may help to accelerate drug discovery by identifying novel drug targets. Published by Elsevier B.V.

The Motivational Appeal of Interactive Storytelling: Towards a Dimensional Model of the User Experience

NASA Astrophysics Data System (ADS)

Roth, Christian; Vorderer, Peter; Klimmt, Christoph

A conceptual account to the quality of the user experience that interactive storytelling intends to facilitate is introduced. Building on socialscientific research from 'old' entertainment media, the experiential qualities of curiosity, suspense, aesthetic pleasantness, self-enhancement, and optimal task engagement ("flow") are proposed as key elements of a theory of user experience in interactive storytelling. Perspectives for the evolution of the model, research and application are briefly discussed.

Interactions between facial emotion and identity in face processing: evidence based on redundancy gains.

PubMed

Yankouskaya, Alla; Booth, David A; Humphreys, Glyn

2012-11-01

Interactions between the processing of emotion expression and form-based information from faces (facial identity) were investigated using the redundant-target paradigm, in which we specifically tested whether identity and emotional expression are integrated in a superadditive manner (Miller, Cognitive Psychology 14:247-279, 1982). In Experiments 1 and 2, participants performed emotion and face identity judgments on faces with sad or angry emotional expressions. Responses to redundant targets were faster than responses to either single target when a universal emotion was conveyed, and performance violated the predictions from a model assuming independent processing of emotion and face identity. Experiment 4 showed that these effects were not modulated by varying interstimulus and nontarget contingencies, and Experiment 5 demonstrated that the redundancy gains were eliminated when faces were inverted. Taken together, these results suggest that the identification of emotion and facial identity interact in face processing.

Modeling plant interspecific interactions from experiments with perennial crop mixtures to predict optimal combinations.

PubMed

Halty, Virginia; Valdés, Matías; Tejera, Mauricio; Picasso, Valentín; Fort, Hugo

2017-12-01

The contribution of plant species richness to productivity and ecosystem functioning is a longstanding issue in ecology, with relevant implications for both conservation and agriculture. Both experiments and quantitative modeling are fundamental to the design of sustainable agroecosystems and the optimization of crop production. We modeled communities of perennial crop mixtures by using a generalized Lotka-Volterra model, i.e., a model such that the interspecific interactions are more general than purely competitive. We estimated model parameters -carrying capacities and interaction coefficients- from, respectively, the observed biomass of monocultures and bicultures measured in a large diversity experiment of seven perennial forage species in Iowa, United States. The sign and absolute value of the interaction coefficients showed that the biological interactions between species pairs included amensalism, competition, and parasitism (asymmetric positive-negative interaction), with various degrees of intensity. We tested the model fit by simulating the combinations of more than two species and comparing them with the polycultures experimental data. Overall, theoretical predictions are in good agreement with the experiments. Using this model, we also simulated species combinations that were not sown. From all possible mixtures (sown and not sown) we identified which are the most productive species combinations. Our results demonstrate that a combination of experiments and modeling can contribute to the design of sustainable agricultural systems in general and to the optimization of crop production in particular. © 2017 by the Ecological Society of America.

Aberration hubs in protein interaction networks highlight actionable targets in cancer.

PubMed

Karimzadeh, Mehran; Jandaghi, Pouria; Papadakis, Andreas I; Trainor, Sebastian; Rung, Johan; Gonzàlez-Porta, Mar; Scelo, Ghislaine; Vasudev, Naveen S; Brazma, Alvis; Huang, Sidong; Banks, Rosamonde E; Lathrop, Mark; Najafabadi, Hamed S; Riazalhosseini, Yasser

2018-05-18

Despite efforts for extensive molecular characterization of cancer patients, such as the international cancer genome consortium (ICGC) and the cancer genome atlas (TCGA), the heterogeneous nature of cancer and our limited knowledge of the contextual function of proteins have complicated the identification of targetable genes. Here, we present Aberration Hub Analysis for Cancer (AbHAC) as a novel integrative approach to pinpoint aberration hubs, i.e. individual proteins that interact extensively with genes that show aberrant mutation or expression. Our analysis of the breast cancer data of the TCGA and the renal cancer data from the ICGC shows that aberration hubs are involved in relevant cancer pathways, including factors promoting cell cycle and DNA replication in basal-like breast tumors, and Src kinase and VEGF signaling in renal carcinoma. Moreover, our analysis uncovers novel functionally relevant and actionable targets, among which we have experimentally validated abnormal splicing of spleen tyrosine kinase as a key factor for cell proliferation in renal cancer. Thus, AbHAC provides an effective strategy to uncover novel disease factors that are only identifiable by examining mutational and expression data in the context of biological networks.

Technically Speaking: On the Structure and Experience of Interaction Involving Augmentative Alternative Communications

ERIC Educational Resources Information Center

Engelke, Christopher Robert

2013-01-01

Technically Speaking: On the Structure and Experience of Interaction Involving Augmentative Alternative Communications examines the ways that communication is structured and experienced by looking at interactions involving augmented communicators--people with severe speech disabilities who use forms of assistive technology in order to communicate…

A network model of genomic hormone interactions underlying dementia and its translational validation through serendipitous off-target effect

PubMed Central

2013-01-01

Background While the majority of studies have focused on the association between sex hormones and dementia, emerging evidence supports the role of other hormone signals in increasing dementia risk. However, due to the lack of an integrated view on mechanistic interactions of hormone signaling pathways associated with dementia, molecular mechanisms through which hormones contribute to the increased risk of dementia has remained unclear and capacity of translating hormone signals to potential therapeutic and diagnostic applications in relation to dementia has been undervalued. Methods Using an integrative knowledge- and data-driven approach, a global hormone interaction network in the context of dementia was constructed, which was further filtered down to a model of convergent hormone signaling pathways. This model was evaluated for its biological and clinical relevance through pathway recovery test, evidence-based analysis, and biomarker-guided analysis. Translational validation of the model was performed using the proposed novel mechanism discovery approach based on ‘serendipitous off-target effects’. Results Our results reveal the existence of a well-connected hormone interaction network underlying dementia. Seven hormone signaling pathways converge at the core of the hormone interaction network, which are shown to be mechanistically linked to the risk of dementia. Amongst these pathways, estrogen signaling pathway takes the major part in the model and insulin signaling pathway is analyzed for its association to learning and memory functions. Validation of the model through serendipitous off-target effects suggests that hormone signaling pathways substantially contribute to the pathogenesis of dementia. Conclusions The integrated network model of hormone interactions underlying dementia may serve as an initial translational platform for identifying potential therapeutic targets and candidate biomarkers for dementia-spectrum disorders such as Alzheimer�

Multi probes measurements at the PALS Facility Research Centre during high intense laser pulse interactions with various target materials

NASA Astrophysics Data System (ADS)

De Marco, Massimo; Krása, Josef; Cikhardt, Jakub; Consoli, Fabrizio; De Angelis, Riccardo; Pfeifer, Miroslav; Krůs, Miroslav; Dostál, Jan; Margarone, Daniele; Picciotto, Antonino; Velyhan, Andriy; Klír, Daniel; Dudžák, Roman; Limpouch, Jiří; Korn, Georg

2018-01-01

During the interaction of high intense laser pulse with solid target, a large amount of hot electrons is produced and a giant Electromagnetic Pulse (EMP) is generated due to the current flowing into the system target-target holder, as well as due to the escaping charged particles in vacuum. EMP production for different target materials is investigated inside and outside the target chamber, using monopole antenna, super wide-band microstrip antenna and Moebius antenna. The EMP consists in a fast transient magnetic field lasting hundreds of nanosecond with frequencies ranging from MHz to tens of GHz. Measurements of magnetic field and return target current in the range of kA were carried out by an inductive target probe (Cikhardt J. et al. Rev. Sci. Instrum. 85 (2014) 103507).

World Business Leaders Interaction in Higher Education: A Novel Experience

ERIC Educational Resources Information Center

Coronel, Gustavo; Mathai, Kathleen

2012-01-01

This article describes a disruptive approach that offers higher education students and faculty the experience of learning from world business leaders and interacting with fellow members at their institutions. The World Business Forum event was transmitted live to 36 higher education institutions in 19 countries. Webcast and social media…

Prototypes and particulars: geometric and experience-dependent spatial categories.

PubMed

Spencer, John P; Hund, Alycia M

2002-03-01

People use geometric cues to form spatial categories. This study investigated whether people also use the spatial distribution of exemplars. Adults pointed to remembered locations on a tabletop. In Experiment 1, a target was placed in each geometric category, and the location of targets was varied. Adults' responses were biased away from a midline category boundary toward geometric prototypes located at the centers of left and right categories. Experiment 2 showed that prototype effects were not influenced by cross-category interactions. In Experiment 3, subsets of targets were positioned at different locations within each category. When prototype effects were removed, there was a bias toward the center of the exemplar distribution, suggesting that common categorization processes operate across spatial and object domains.

Experiments on the interaction of heavy ions with dense plasma at GSI-Darmstadt

NASA Astrophysics Data System (ADS)

Stöckl, C.; Boine-Frankenheim, O.; Geißel, M.; Roth, M.; Wetzler, H.; Seelig, W.; Iwase, O.; Spiller, P.; Bock, R.; Süß, W.; Hoffmann, D. H. H.

One of the main objectives of the experimental plasma physics activities at the Gesellschaft für Schwerionenforschung (GSI) are the interaction processes of heavy ions with dense ionized matter. Gas-discharge plasma targets were used for energy loss and charge state measurements in a regime of electron density and temperature up to 10 19 cm -3 and 20 eV, respectively. An improved model of the charge exchange processes in fully ionized hydrogen plasma, taking into account multiple excited electronic configurations which subsequently ionize, has removed the discrepancies of previous theoretical descriptions. The energy loss of the ion beam in partially ionized plasmas such as argon was found to agree very well with our simple theoretical model based on the modified Bethe-Bloch theory. A new setup with a 100 J/5 GW Nd-glass laser now provides access to density ranges up to 10 21 cm -3 and temperatures of up to 100 eV. First results of interaction experiments with laser-produced plasma are presented. To fully exploit the experimental possibilities of the new laser-plasma setup both improved charge state detection systems and better plasma diagnostics are indispensable. Present developments and future possibilities in these fields are presented. This paper summarizes the following contributions: Interaction of heavy-ion beams with laser plasma by C. Stöckl et al. Energy Loss of Heavy Ions in a laser-produced plasma by M. Roth et al. Charge state measurements of heavy ions passing a laser produced plasma with high time resolution by W. Süß et al. Plasma diagnostics for laser-produced plasma by O. Iwase et al. Future possibilities of plasma diagnostics at GSI by M. Geißel et al.

Biomimicking Platelet-Monocyte Interactions as a Novel Targeting Strategy for Heart Healing.

PubMed

Cheng, Bill; Toh, Elsie K W; Chen, Kun-Hung; Chang, Yuan-Chih; Hu, Che-Ming J; Wu, Han-Chung; Chau, Lee-Young; Chen, Peilin; Hsieh, Patrick C H

2016-10-01

In patients who survive myocardial infarction, many go on to develop congestive heart failure (CHF). Despite ongoing efforts to develop new approaches for postinfarction therapy, there are still no effective therapeutic options available to CHF patients. Currently, the delivery of cardioprotective drugs relies entirely on passive uptake via the enhanced permeability and retention (EPR) effect which occurs in proximity to the infarction site. However, in ischemic disease, unlike in cancer, the EPR effect only exists for a short duration postinfarction and thus insufficient for meaningful cardioprotection. Splenic monocytes are recruited to the heart in large numbers postinfarction, and are known to interact with platelets during circulation. Therefore, the strategy is to exploit this interaction by developing platelet-like proteoliposomes (PLPs), biomimicking platelet interactions with circulating monocytes. PLPs show strong binding affinity for monocytes but not for endothelial cells in vitro, mimicking normal platelet activity. Furthermore, intravital multiphoton imaging shows that comparing to plain liposomes, PLPs do not aggregate on uninjured endothelium but do accumulate at the injury site 72 h postinfarction. Importantly, PLPs enhance the targeting of anti-inflammatory drug, cobalt protoporphyrin, to the heart in an EPR-independent manner, which result in better therapeutic outcome. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of a Neutronic Experiment on a Simulated Mercury Spallation Neutron Target Assembly Bombarded by Giga-Electron-Volt Protons

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

Maekawa, Fujio; Meigo, Shin-ichiro; Kasugai, Yoshimi

2005-05-15

A neutronic benchmark experiment on a simulated spallation neutron target assembly was conducted by using the Alternating Gradient Synchrotron at Brookhaven National Laboratory and was analyzed to investigate the prediction capability of Monte Carlo simulation codes used in neutronic designs of spallation neutron sources. The target assembly consisting of a mercury target, a light water moderator, and a lead reflector was bombarded by 1.94-, 12-, and 24-GeV protons, and the fast neutron flux distributions around the target and the spectra of thermal neutrons leaking from the moderator were measured in the experiment. In this study, the Monte Carlo particle transportmore » simulation codes NMTC/JAM, MCNPX, and MCNP-4A with associated cross-section data in JENDL and LA-150 were verified based on benchmark analysis of the experiment. As a result, all the calculations predicted the measured quantities adequately; calculated integral fluxes of fast and thermal neutrons agreed approximately within {+-}40% with the experiments although the overall energy range encompassed more than 12 orders of magnitude. Accordingly, it was concluded that these simulation codes and cross-section data were adequate for neutronics designs of spallation neutron sources.« less

Engineering aspect of the Microwave Ionosphere Nonlinear Interaction Experiment (MINIX) with a sounding rocket

NASA Astrophysics Data System (ADS)

Nagatomo, M.; Kaya, N.; Matsumoto, H.

1984-10-01

One type of problem arising in connection with an evaluation of the feasibility of the Solar Power Satellite (SPS) and the definition of suitable SPS designs is related to environmental issues. Questions exist, for instance, regarding the interaction between microwave power and the upper atmosphere. The present investigation is concerned with the Microwave Ionosphere Nonlinear Interaction Experiment (MINIX), which is a space plasma experiment originally devoted to the research of space plasma physics. MINIX is eventually to observe possible effects of a strong microwave field in the ionospheric environment. The scientific requirements of the MINIX are discussed, taking into account functional and experimental conditions. Attention is also given to rocket characteristics, experimental design, the payload, the inflight experiment configuration, and details concerning the conduction of the experiment.

Docking and scoring protein interactions: CAPRI 2009.

PubMed

Lensink, Marc F; Wodak, Shoshana J

2010-11-15

Protein docking algorithms are assessed by evaluating blind predictions performed during 2007-2009 in Rounds 13-19 of the community-wide experiment on critical assessment of predicted interactions (CAPRI). We evaluated the ability of these algorithms to sample docking poses and to single out specific association modes in 14 targets, representing 11 distinct protein complexes. These complexes play important biological roles in RNA maturation, G-protein signal processing, and enzyme inhibition and function. One target involved protein-RNA interactions not previously considered in CAPRI, several others were hetero-oligomers, or featured multiple interfaces between the same protein pair. For most targets, predictions started from the experimentally determined structures of the free (unbound) components, or from models built from known structures of related or similar proteins. To succeed they therefore needed to account for conformational changes and model inaccuracies. In total, 64 groups and 12 web-servers submitted docking predictions of which 4420 were evaluated. Overall our assessment reveals that 67% of the groups, more than ever before, produced acceptable models or better for at least one target, with many groups submitting multiple high- and medium-accuracy models for two to six targets. Forty-one groups including four web-servers participated in the scoring experiment with 1296 evaluated models. Scoring predictions also show signs of progress evidenced from the large proportion of correct models submitted. But singling out the best models remains a challenge, which also adversely affects the ability to correctly rank docking models. With the increased interest in translating abstract protein interaction networks into realistic models of protein assemblies, the growing CAPRI community is actively developing more efficient and reliable docking and scoring methods for everyone to use. © 2010 Wiley-Liss, Inc.

Plasma-wall interaction data needs critical to a Burning Core Experiment (BCX)

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

Not Available

1985-11-01

The Division of Development and Technology has sponsored a four day US-Japan workshop ''Plasma-Wall Interaction Data Needs Critical to a Burning Core Experiment (BCX)'', held at Sandia National Laboratories, Livermore, California on June 24 to 27, 1985. The workshop, which brought together fifty scientists and engineers from the United States, Japan, Germany, and Canada, considered the plasma-material interaction and high heat flux (PMI/HHF) issues for the next generation of magnetic fusion energy devices, the Burning Core Experiment (BCX). Materials options were ranked, and a strategy for future PMI/HHF research was formulated. The foundation for international collaboration and coordination of thismore » research was also established. This volume contains the last three of the five technical sessions. The first of the three is on plasma materials interaction issues, the second is on research facilities and the third is from smaller working group meetings on graphite, beryllium, advanced materials and future collaborations.« less

Debris-free soft x-ray source with gas-puff target

NASA Astrophysics Data System (ADS)

Ni, Qiliang; Chen, Bo; Gong, Yan; Cao, Jianlin; Lin, Jingquan; Lee, Hongyan

2001-12-01

We have been developing a debris-free laser plasma light source with a gas-puff target system whose nozzle is driven by a piezoelectric crystal membrane. The gas-puff target system can utilize gases such as CO2, O2 or some gas mixture according to different experiments. Therefore, in comparison with soft X-ray source using a metal target, after continuously several-hour laser interaction with gas from the gas-puff target system, no evidences show that the light source can produce debris. The debris-free soft X-ray source is prepared for soft X-ray projection lithography research at State Key Laboratory of Applied Optics. Strong emission from CO2, O2 and Kr plasma is observed.

Baby MIND: A Magnetised Spectrometer for the WAGASCI Experiment

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

Antonova, M.; et al.

The WAGASCI experiment being built at the J-PARC neutrino beam line will measure the difference in cross sections from neutrinos interacting with a water and scintillator targets, in order to constrain neutrino cross sections, essential for the T2K neutrino oscillation measurements. A prototype Magnetised Iron Neutrino Detector (MIND), called Baby MIND, is being constructed at CERN to act as a magnetic spectrometer behind the main WAGASCI target to be able to measure the charge and momentum of the outgoing muon from neutrino charged current interactions.

Genome-wide identification of translationally inhibited and degraded miR-155 targets using RNA-interacting protein-IP

PubMed Central

Meier, Jan; Hovestadt, Volker; Zapatka, Marc; Pscherer, Armin; Lichter, Peter; Seiffert, Martina

2013-01-01

MicroRNAs (miRNAs) are single-stranded, small, non-coding RNAs, which fine-tune protein expression by degrading and/or translationally inhibiting mRNAs. Manipulation of miRNA expression in animal models frequently results in severe phenotypes indicating their relevance in controlling cellular functions, most likely by interacting with multiple targets. To better understand the effect of miRNA activities, genome-wide analysis of their targets are required. MicroRNA profiling as well as transcriptome analysis upon enforced miRNA expression were frequently used to investigate their relevance. However, these approaches often fail to identify relevant miRNAs targets. Therefore, we tested the precision of RNA-interacting protein immunoprecipitation (RIP) using AGO2-specific antibodies, a core component of the “RNA-induced silencing complex” (RISC), followed by RNA sequencing (Seq) in a defined cellular system, the HEK293T cells with stable, ectopic expression of miR-155. Thereby, we identified 100 AGO2-associated mRNAs in miR-155-expressing cells, of which 67 were in silico predicted miR-155 target genes. An integrated analysis of the corresponding expression profiles indicated that these targets were either regulated by mRNA decay or by translational repression. Of the identified miR-155 targets, 17 were related to cell cycle control, suggesting their involvement in the observed increase in cell proliferation of HEK293T cells upon miR-155 expression. Additional, secondary changes within the gene expression profile were detected and might contribute to this phenotype as well. Interestingly, by analyzing RIP-Seq data of HEK-293T cells and two B-cell lines we identified a recurrent disproportional enrichment of several miRNAs, including miR-155 and miRNAs of the miR-17-92 cluster, in the AGO2-associated precipitates, suggesting discrepancies in miRNA expression and activity. PMID:23673373

Monte Carlo studies on photon interactions in radiobiological experiments

PubMed Central

Shahmohammadi Beni, Mehrdad; Krstic, D.; Nikezic, D.

2018-01-01

X-ray and γ-ray photons have been widely used for studying radiobiological effects of ionizing radiations. Photons are indirectly ionizing radiations so they need to set in motion electrons (which are a directly ionizing radiation) to perform the ionizations. When the photon dose decreases to below a certain limit, the number of electrons set in motion will become so small that not all cells in an “exposed” cell population can get at least one electron hit. When some cells in a cell population are not hit by a directly ionizing radiation (in other words not irradiated), there will be rescue effect between the irradiated cells and non-irradiated cells, and the resultant radiobiological effect observed for the “exposed” cell population will be different. In the present paper, the mechanisms underlying photon interactions in radiobiological experiments were studied using our developed NRUphoton computer code, which was benchmarked against the MCNP5 code by comparing the photon dose delivered to the cell layer underneath the water medium. The following conclusions were reached: (1) The interaction fractions decreased in the following order: 16O > 12C > 14N > 1H. Bulges in the interaction fractions (versus water medium thickness) were observed, which reflected changes in the energies of the propagating photons due to traversals of different amount of water medium as well as changes in the energy-dependent photon interaction cross-sections. (2) Photoelectric interaction and incoherent scattering dominated for lower-energy (10 keV) and high-energy (100 keV and 1 MeV) incident photons. (3) The fractions of electron ejection from different nuclei were mainly governed by the photoelectric effect cross-sections, and the fractions from the 1s subshell were the largest. (4) The penetration fractions in general decreased with increasing medium thickness, and increased with increasing incident photon energy, the latter being explained by the corresponding reduction in

A new multimodal interactive way of subjective scoring of 3D video quality of experience

NASA Astrophysics Data System (ADS)

Kim, Taewan; Lee, Kwanghyun; Lee, Sanghoon; Bovik, Alan C.

2014-03-01

People that watch today's 3D visual programs, such as 3D cinema, 3D TV and 3D games, experience wide and dynamically varying ranges of 3D visual immersion and 3D quality of experience (QoE). It is necessary to be able to deploy reliable methodologies that measure each viewers subjective experience. We propose a new methodology that we call Multimodal Interactive Continuous Scoring of Quality (MICSQ). MICSQ is composed of a device interaction process between the 3D display and a separate device (PC, tablet, etc.) used as an assessment tool, and a human interaction process between the subject(s) and the device. The scoring process is multimodal, using aural and tactile cues to help engage and focus the subject(s) on their tasks. Moreover, the wireless device interaction process makes it possible for multiple subjects to assess 3D QoE simultaneously in a large space such as a movie theater, and at di®erent visual angles and distances.

Social setting, intuition and experience in laboratory experiments interact to shape cooperative decision-making

PubMed Central

Capraro, Valerio; Cococcioni, Giorgia

2015-01-01

Recent studies suggest that cooperative decision-making in one-shot interactions is a history-dependent dynamic process: promoting intuition versus deliberation typically has a positive effect on cooperation (dynamism) among people living in a cooperative setting and with no previous experience in economic games on cooperation (history dependence). Here, we report on a laboratory experiment exploring how these findings transfer to a non-cooperative setting. We find two major results: (i) promoting intuition versus deliberation has no effect on cooperative behaviour among inexperienced subjects living in a non-cooperative setting; (ii) experienced subjects cooperate more than inexperienced subjects, but only under time pressure. These results suggest that cooperation is a learning process, rather than an instinctive impulse or a self-controlled choice, and that experience operates primarily via the channel of intuition. Our findings shed further light on the cognitive basis of human cooperative decision-making and provide further support for the recently proposed social heuristics hypothesis. PMID:26156762

The application of an MPM-MFM method for simulating weapon-target interaction.

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

Ma, X.; Zou, Q.; Zhang, D. Z.

2005-01-01

During the past two decades, Los Alamos National Laboratory (LANL) has developed computational algorithms and software for analysis of multiphase flow suitable for high-speed projectile penetration of metallic and nonmetallic materials, using a material point method (MPM)-multiphase flow method (MFM). Recently, ACTA has teamed with LANL to advance a computational algorithm for simulating complex weapon-target interaction for penetrating and exploding munitions, such as tank rounds and artillery shells, as well as non-exploding kinetic energy penetrators. This paper will outline the mathematical basis for the MPM-MFM method as implemented in LANL's CartaBlanca code. CartaBlanca, written entirely in Java using object-oriented design,more » is used to solve complex problems involving (a) failure and penetration of solids, (b) heat transfer, (c) phase change, (d) chemical reactions, and (e) multiphase flow. We will present its application to the penetration of a steel target by a tungsten cylinder and compare results with time-resolved experimental data published by Anderson, et. al., Int. J. Impact Engng., Vol. 16, No. 1, pp. 1-18, 1995.« less

Laboratory plasma interactions experiments: Results and implications to future space systems

NASA Technical Reports Server (NTRS)

Leung, Philip

1986-01-01

The experimental results discussed show the significance of the effects caused by spacecraft plasma interactions, in particular the generation of Electromagnetic Interference. As the experimental results show, the magnitude of the adverse effects induced by Plasma Interactions (PI) will be more significant for spacecraft of the next century. Therefore, research is needed to control possible adverse effects. Several techniques to control the selected PI effects are discussed. Tests, in the form of flight experiments, are needed to validate these proposed ideas.

Interaction Analysis through Proteomic Phage Display

PubMed Central

2014-01-01

Phage display is a powerful technique for profiling specificities of peptide binding domains. The method is suited for the identification of high-affinity ligands with inhibitor potential when using highly diverse combinatorial peptide phage libraries. Such experiments further provide consensus motifs for genome-wide scanning of ligands of potential biological relevance. A complementary but considerably less explored approach is to display expression products of genomic DNA, cDNA, open reading frames (ORFs), or oligonucleotide libraries designed to encode defined regions of a target proteome on phage particles. One of the main applications of such proteomic libraries has been the elucidation of antibody epitopes. This review is focused on the use of proteomic phage display to uncover protein-protein interactions of potential relevance for cellular function. The method is particularly suited for the discovery of interactions between peptide binding domains and their targets. We discuss the largely unexplored potential of this method in the discovery of domain-motif interactions of potential biological relevance. PMID:25295249

Interaction of Object Binding Cues in Binaural Masking Pattern Experiments.

PubMed

Verhey, Jesko L; Lübken, Björn; van de Par, Steven

2016-01-01

Object binding cues such as binaural and across-frequency modulation cues are likely to be used by the auditory system to separate sounds from different sources in complex auditory scenes. The present study investigates the interaction of these cues in a binaural masking pattern paradigm where a sinusoidal target is masked by a narrowband noise. It was hypothesised that beating between signal and masker may contribute to signal detection when signal and masker do not spectrally overlap but that this cue could not be used in combination with interaural cues. To test this hypothesis an additional sinusoidal interferer was added to the noise masker with a lower frequency than the noise whereas the target had a higher frequency than the noise. Thresholds increase when the interferer is added. This effect is largest when the spectral interferer-masker and masker-target distances are equal. The result supports the hypothesis that modulation cues contribute to signal detection in the classical masking paradigm and that these are analysed with modulation bandpass filters. A monaural model including an across-frequency modulation process is presented that account for this effect. Interestingly, the interferer also affects dichotic thresholds indicating that modulation cues also play a role in binaural processing.

Dynamically polarized target for the g p 2 and G p E experiments at Jefferson Lab

DOE PAGES

Pierce, J.; Maxwell, J.; Badman, T.; ...

2013-12-16

We describe a dynamically polarized target that has been utilized for two electron scattering experiments in Hall A at Jefferson Lab. The primary components of the target are a new, high cooling power 4 He evaporation refrigerator, and a re-purposed, superconducting split-coil magnet. It has been used to polarize protons in irradiated NH 3 at a temperature of 1 K and at fields of 2.5 and 5.0 Tesla. The performance of the target material in the electron beam under these conditions will be discussed. The maximum polarizations of 28% and 95% were obtained at those fields, respectively. To satisfy themore » requirements of both experiments, the magnet had to be routinely rotated between angles of 0, 6, and 90 degrees with respect to the incident electron beam. This was accomplished using a new rotating vacuum seal which permits rotations to be performed in only a few minutes.« less

Implosion and heating experiments of fast ignition targets by Gekko-XII and LFEX lasers

NASA Astrophysics Data System (ADS)

Shiraga, H.; Fujioka, S.; Nakai, M.; Watari, T.; Nakamura, H.; Arikawa, Y.; Hosoda, H.; Nagai, T.; Koga, M.; Kikuchi, H.; Ishii, Y.; Sogo, T.; Shigemori, K.; Nishimura, H.; Zhang, Z.; Tanabe, M.; Ohira, S.; Fujii, Y.; Namimoto, T.; Sakawa, Y.; Maegawa, O.; Ozaki, T.; Tanaka, K. A.; Habara, H.; Iwawaki, T.; Shimada, K.; Key, M.; Norreys, P.; Pasley, J.; Nagatomo, H.; Johzaki, T.; Sunahara, A.; Murakami, M.; Sakagami, H.; Taguchi, T.; Norimatsu, T.; Homma, H.; Fujimoto, Y.; Iwamoto, A.; Miyanaga, N.; Kawanaka, J.; Kanabe, T.; Jitsuno, T.; Nakata, Y.; Tsubakimoto, K.; Sueda, K.; Kodama, R.; Kondo, K.; Morio, N.; Matsuo, S.; Kawasaki, T.; Sawai, K.; Tsuji, K.; Murakami, H.; Sarukura, N.; Shimizu, T.; Mima, K.; Azechi, H.

2013-11-01

The FIREX-1 project, the goal of which is to demonstrate fuel heating up to 5 keV by fast ignition scheme, has been carried out since 2003 including construction and tuning of LFEX laser and integrated experiments. Implosion and heating experiment of Fast Ignition targets have been performed since 2009 with Gekko-XII and LFEX lasers. A deuterated polystyrene shell target was imploded with the 0.53- μm Gekko-XII, and the 1.053- μm beam of the LFEX laser was injected through a gold cone attached to the shell to generate hot electrons to heat the imploded fuel plasma. Pulse contrast ratio of the LFEX beam was significantly improved. Also a variety of plasma diagnostic instruments were developed to be compatible with harsh environment of intense hard x-rays (γ rays) and electromagnetic pulses due to the intense LFEX beam on the target. Large background signals around the DD neutron signal in time-of-flight record of neutron detector were found to consist of neutrons via (γ,n) reactions and scattered gamma rays. Enhanced neutron yield was confirmed by carefully eliminating such backgrounds. Neutron enhancement up to 3.5 × 107 was observed. Heating efficiency was estimated to be 10-20% assuming a uniform temperature rise model.

Students' experiences with interactivity and learning in a high school physics multimedia distance learning course

NASA Astrophysics Data System (ADS)

Villarreal-Stewart, Irene

The purpose guiding this research has been to learn about and describe the phenomena of interactivity from the learners' perspectives and to learn which of the interactivity affordances and practices were actually used by students and why in the process of learning physics using an interactive multimedia distance learning course system. The bigger purpose behind learning about and describing interactivity has been to gain knowledge and perspective for its instructional design to benefit the learner, the school as curriculum implementer, and instructional media designers to create better products. Qualitative methodology in the interpretivist tradition was used, that is, in-depth interviews and on-site observations, to gain understanding of interactivity from the learners' perspective and to gain understanding of the student learning context impacting and shaping the students' interactivity experiences. NVivo was used to sort, organize and index data. All data were read on three levels: literally, interpretively, and reflexively; and were read comparatively to other perspectives to get descriptions and interpretations that were holistic to the implementation and had potential insight to improve practice for instructional designers, teachers, administrators, specifically to improve the learning experience for students. Site-Specific Findings: Students watched videos, resisted using phone and e-mail, and worked math problems to demonstrate learning, which resulted in very little interactivity, virtually no dialogue about physics, no physical activity, one-way communication, multifaceted dissatisfaction, student need for teacher involvement in the learning enterprise, student appreciation for interactivity, and expressed desire for a real, live teacher. I also found that some students did experience the system as interactive, did experience learner control and self-directed learning, and despite dissatisfaction, liked and appreciated the course. Wider Applications

Dynamically polarized target for the g {2/ p } and G {/E p } experiments at Jefferson Lab

NASA Astrophysics Data System (ADS)

Pierce, J.; Maxwell, J.; Keith, C.

2014-01-01

Recently, two experiments were concluded in Hall A at Jefferson Lab which utilized a newly assembled, solid, polarized hydrogen target. The primary components of the target are a new, high cooling power 4He evaporation refrigerator, and a re-purposed, superconducting split-coil magnet. It has been used to polarize protons in irradiated NH3 at a temperature of 1 K and at fields of 2.5 and 5.0 tesla. Maximum polarizations of 55% and 95% were obtained at those fields, respectively. To satisfy the requirements of both experiments, the magnet had to be routinely rotated between angles of 0°, 6°, and 90° with respect to the incident electron beam.

Tyrosine dephosphorylation enhances the therapeutic target activity of epidermal growth factor receptor (EGFR) by disrupting its interaction with estrogen receptor (ER).

PubMed

Ma, Shao; Yin, Ning; Qi, Xiaomei; Pfister, Sandra L; Zhang, Mei-Jie; Ma, Rong; Chen, Guan

2015-05-30

Protein-protein interactions can increase or decrease its therapeutic target activity and the determining factors involved, however, are largely unknown. Here, we report that tyrosine-dephosphorylation of epidermal growth factor receptor (EGFR) increases its therapeutic target activity by disrupting its interaction with estrogen receptor (ER). Protein tyrosine phosphatase H1 (PTPH1) dephosphorylates the tyrosine kinase EGFR, disrupts its interaction with the nuclear receptor ER, and increases breast cancer sensitivity to small molecule tyrosine kinase inhibitors (TKIs). These effects require PTPH1 catalytic activity and its interaction with EGFR, suggesting that the phosphatase may increase the sensitivity by dephosphorylating EGFR leading to its dissociation with ER. Consistent with this notion, a nuclear-localization defective ER has a higher EGFR-binding activity and confers the resistance to TKI-induced growth inhibition. Additional analysis show that PTPH1 stabilizes EGFR, stimulates the membranous EGFR accumulation, and enhances the growth-inhibitory activity of a combination therapy of TKIs with an anti-estrogen. Since EGFR and ER both are substrates for PTPH1 in vitro and in intact cells, these results indicate that an inhibitory EGFR-ER protein complex can be switched off through a competitive enzyme-substrate binding. Our results would have important implications for the treatment of breast cancer with targeted therapeutics.

Laser-plasma extreme ultraviolet and soft X-ray sources based on a double stream gas puff target: interaction of the radiation pulses with matter

NASA Astrophysics Data System (ADS)

Bartnik, A.

2015-06-01

In this work a review of investigations concerning interaction of intense extreme ultraviolet (EUV) and soft X-ray (SXR) pulses with matter is presented. The investigations were performed using laser-produced plasma (LPP) EUV/SXR sources based on a double stream gas puff target. The sources are equipped with dedicated collectors allowing for efficient focusing of the EUV/SXR radiation pulses. Intense radiation in a wide spectral range, as well as a quasi-monochromatic radiation can be produced. In the paper different kinds of LPP EUV/SXR sources developed in the Institute of Optoelectronics, Military University of Technology are described. Radiation intensities delivered by the sources are sufficient for different kinds of interaction experiments including EUV/SXR induced ablation, surface treatment, EUV fluorescence or photoionized plasma creation. A brief review of the main results concerning this kind of experiments performed by author of the paper are presented. However, since the LPP sources cannot compete with large scale X-ray sources like synchrotrons, free electron lasers or high energy density plasma sources, it was indicated that some investigations not requiring extreme irradiation parameters can be performed using the small scale installations. Some results, especially concerning low temperature photoionized plasmas are very unique and could be hardly obtained using the large facilities.

Manifestation of anharmonic resonance in the interaction of intense ultrashort laser pulses with microstructured targets

NASA Astrophysics Data System (ADS)

Dalui, Malay; Kundu, M.; Madhu Trivikram, T.; Ray, Krishanu; Krishnamurthy, M.

2016-10-01

Identification of the basic processes responsible for an efficient heating of intense laser produced plasmas is one of the important features of high intensity laser matter interaction studies. Collisionless absorption due to the anharmonicity in the self-consistent electrostatic potential of the plasma, known as anharmonic resonance (AHR), has been proposed to be a basic mechanism but a clear experimental demonstration is needed. Here, we show that microstructured targets enhance X-ray emission and the polarization dependence ascribes the enhancement to anharmonic resonance heating. It is found that p-polarized pulses of 5 ×1017 W/cm2 intensity bring in a 16-fold enhancement in the X-ray emission in the energy range 20-350 keV compared to s-polarized pulses with microstructured targets. This ratio is 2 for the case of polished targets under otherwise identical conditions. Particle-in-cell simulations clearly show that AHR is the key absorption mechanism responsible for this effect.

The impact of real-time, Internet experiments versus interactive, asynchronous replays of experiments on high school students science concepts and attitudes

NASA Astrophysics Data System (ADS)

Kubasko, Dennis S., Jr.

The purpose of this study was to investigate whether students' learning experiences were similar or different with an interactive, live connection via the Internet in real-time to an Atomic Force Microscope (AFM) versus a stored replay of AFM experiments. Did the two treatments influence students' attitudes towards the learning experience? Are there differences in students' understandings of viruses and science investigations? In addition, this study investigated treatment effects on students' understandings of the nature of science. The present study drew upon the research that examined students' attitudes toward science, students' views of the nature of science, instructional technology in education, and prior research on the nanoManipulator. Specific efforts have been made to address reform efforts in science education throughout the literature review. Eighty-five high school biology students participated in the nanoManipulator experience (44 males, 41 females, 64 Euro-American, 16 African-American, and 5 of other ethnicities). Two high school classes were randomly selected and administered the interactive, real-time treatment. Two different high school classes were randomly selected and administered the limited-interaction, experimental replay treatment. The intervention occurred over a one-week period. Qualitative and quantitative measures were used to examine the differences between two treatment conditions. Experiential, affective, cognitive, and the nature of science domains were assessed. Findings show that the questions and statements made in synchronous time by the live treatment group were significantly different than students' questions and statements in asynchronous communication. Students in the replay treatment made more statements about what they learned or knew about the experience than did students in the live experience. Students in both groups showed significant gains in understanding viruses (particularly viral dimensionality and shape

Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

PubMed Central

Madaan, Kanika; Kumar, Sandeep; Poonia, Neelam; Lather, Viney; Pandita, Deepti

2014-01-01

Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity. PMID:25035633

The not-so-sterile 4th neutrino: constraints on new gauge interactions from neutrino oscillation experiments

NASA Astrophysics Data System (ADS)

Kopp, Joachim; Welter, Johannes

2014-12-01

Sterile neutrino models with new gauge interactions in the sterile sector are phenomenologically interesting since they can lead to novel effects in neutrino oscillation experiments, in cosmology and in dark matter detectors, possibly even explaining some of the observed anomalies in these experiments. Here, we use data from neutrino oscillation experiments, in particular from MiniBooNE, MINOS and solar neutrino experiments, to constrain such models. We focus in particular on the case where the sterile sector gauge boson A ' couples also to Standard Model particles (for instance to the baryon number current) and thus induces a large Mikheyev-Smirnov-Wolfenstein potential. For eV-scale sterile neutrinos, we obtain strong constraints especially from MINOS, which restricts the strength of the new interaction to be less than ˜ 10 times that of the Standard Model weak interaction unless active-sterile neutrino mixing is very small (sin2 θ 24 ≲ 10-3). This rules out gauge forces large enough to affect short-baseline experiments like MiniBooNE and it imposes nontrivial constraints on signals from sterile neutrino scattering in dark matter experiments.