Medium-scale melt-sodium fragmentation experiments

International Nuclear Information System (INIS)

Chu, T.Y.; Beattie, A.G.; Drotning, W.D.; Powers, D.A.

1979-01-01

The results of a series of fragmentation experiments involving up to 20 Kg of thermitically produced high temperature melts and 23 Kg of sodium are presented. Except for one experiment where some centimeter size particles are observed, the fragment distributions seem to be in the range of previous data. Spatial distribution of the fragments in the debris bed appears to be stratified. Scanning electron micrographs of fragments indicate fragmentation to be occurring in the molten state for the more intense interactions observed. Interaction data obtained show quiescent periods of 0.5 to 1.5 second between pressure pulses. The force impulse values per unit mass of melt seems to be in the same range as previous experiments

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

Science.gov (United States)

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug

The multi-step prompt particle emission from fission fragments

International Nuclear Information System (INIS)

Zhivopistsev, A.; Oprea, C.; Oprea, I.

2003-01-01

The purpose of this work is the study of non-equilibrium high-energy gamma emission from 252 Cf. In the framework of the formalism of statistical multi-step compound processes in nuclear reactions. A relation was found between the shape of the high-energy part of the gamma spectrum and different mechanisms of excitation of the fission fragments. Agreement with experimental data for different groups of fission fragments was obtained. The analysis of the experimental high-energy part of gamma spectra yields information about the mechanism of excitation of fission fragments. The influence of dissipation of the deformation excess on intrinsic excitation of fission fragments was studied. (authors)

Antipodal fragment velocities for porous and weak targets at catastrophic impacts

Science.gov (United States)

Yanagisawa, M.; Itoi, T.

1993-03-01

Mortar, porous alumina, and sand targets, which were spherical in shape and from 11 to 15 cm in diameter, were impacted normally by plastic (polycarbonate) projectiles of nearly 1 g in mass at velocities about 6 km/s. Fragment velocity at the antipole of impact site (antipodal velocity, V(sub a)), for each experiment, was obtained from two Flash X-ray images recorded prior to and at predetermined delayed time after impact event. It has been revealed that the velocities for the same E/M(sub t) (impact energy divided by target mass) depend strongly on target material, and differ about an order of magnitude between the sand and basalt.

Multi-fragment visibility determination in the context of order-independent transparency rendering

OpenAIRE

Marilena Maule

2015-01-01

Multi-fragment effects, in the computer-generated imagery context, are effects that determine pixel color based on information computed from more than one fragment. In such effects, the contribution of each fragment is extracted from its visibility with respect to a point of view. Seen through a pixel’s point of view, the visibility of one fragment depends on its spatial relationship with other fragments. This relationship can be reduced to the problem of sorting multiple fragments. Therefore...

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

Science.gov (United States)

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

Target fragmentation in 1 A GeV Au + Pb reaction

CERN Document Server

Grabez, B

1999-01-01

We investigated the production of target fragments in interaction of 1 A GeV Au projectile with Pb. The behaviour of the atomic numbers of fragments and of the relative velocities has been examined in dependence of the centrality of collision. The results have been compared with the data of other authors obtained for projectile fragmentation.

Targeting incentives to reduce habitat fragmentation

Science.gov (United States)

David Lewis; Andrew Plantinga; Junjie Wu

2009-01-01

This article develops a theoretical model to analyze the spatial targeting of incentives for the restoration of forested landscapes when wildlife habitat can be enhanced by reducing fragmentation. The key theoretical result is that the marginal net benefits of increasing forest can be convex, in which case corner solutions--converting either none or all of the...

Cumulative protons in 12C fragmentation at intermediate energy

International Nuclear Information System (INIS)

Abramov, B.M.; Alekseev, P.N.; Borodin, Y.A.; Bulychjov, S.A.; Dukhovskoi, I.A.; Khanov, A.I.; Krutenkova, A.P.; Kulikov, V.V.; Martemianov, M.A.; Matsuk, M.A.; Turdakina, E.N.

2014-01-01

In the FRAGM experiment at heavy ion accelerator complex TWAC-ITEP, the proton yields at an angle 3.5 degrees have been measured in fragmentation of carbon ions at T 0 equals 0.3, 0.6, 0.95 and 2.0 GeV/nucleon on beryllium target. The data are presented as invariant proton yields on cumulative variable x in the range 0.9 < x < 2.4. Proton spectra cover six orders of invariant cross section magnitude. They have been analyzed in the framework of quark cluster fragmentation model. Fragmentation functions of quark- gluon string model are used. The probabilities of the existence of multi-quark clusters in carbon nuclei are estimated to be 8 - 12% for six-quark clusters and 0.2 - 0.6% for nine- quark clusters. (authors)

Inclusive characteristics of the nuclear target fragmentation products induced by relativistic particles

International Nuclear Information System (INIS)

Bogatin, V.I.; Ganza, E.A.; Lozhkin, O.V.; Murin, Yu.A.; Oplavin, V.S.; Perfilov, N.A.; Yakovlev, Yu.P.

1981-01-01

An experimental investigation of inclusive characteristics of nuclei-target fragmentation is conducted for further development and test of physical value of the earlier suggested nuclear fragmentation model based on the connection of the fragmentation with fluctuations of the quasiparticle density in the two-component quantum liquid, an experimental investigation of the inclusive characteristics of the nuclei-target fragmentation is carried out. The processes of sup(3, 4, 6, 8)He and sup(6, 7, 8, 9, 11)Li fragment formation during the interaction of relativistic protons (Esub(p)=6.7 GeV) and deutrons (Esub(d)=3.1 GeV) with 112 Sn and 124 Sn isotopes are studied by the method of semiconductive ΔE-E detectors. Differential energy spectra of fragments and isotopic ratio of cross sections of their formation as well as data on the dependence of isotopic ratios of fragmentation cross sections on the energy of incident particles and on the fragment energy are obtained. Presented is a phenomenological model of fragmentation within the frames of which the obtained experimental data are analyzed [ru

Box-Particle Cardinality Balanced Multi-Target Multi-Bernoulli Filter

OpenAIRE

L. Song; X. Zhao

2014-01-01

As a generalized particle filtering, the box-particle filter (Box-PF) has a potential to process the measurements affected by bounded error of unknown distributions and biases. Inspired by the Box-PF, a novel implementation for multi-target tracking, called box-particle cardinality balanced multi-target multi-Bernoulli (Box-CBMeMBer) filter is presented in this paper. More important, to eliminate the negative effect of clutters in the estimation of the numbers of targets, an improved generali...

Multi-fragmentation of C60 induced by 4He2+ impact (E<60 keV/amu) and investigated by a multi-correlation technique

International Nuclear Information System (INIS)

Rentenier, A.; Moretto-Capelle, P.; Bordenave-Montesquieu, D.; Bordenave-Montesquieu, A.

2003-01-01

In this communication, the C 60 multi-fragmentation induced by 4 He 2+ ion impact in the 20-240 keV energy range, is investigated. Using a multi-stop time-of-flight technique, it becomes possible to measure partial spectra corresponding to the simultaneous emission of 2-5 light charged fragments; small charged fragments are found to be accompanied by the emission of at least another one. The fragment size distribution depends on the collisional energy and the multiplicity of emitted charged fragments. It is more peaked on small sizes when the collision velocity or the multiplicity increases. Corresponding relative cross sections are also measured; processes with emission of 2 and 3 charged fragments are always dominant but their relative weights decrease slowly when the collision energy increases

Development of Fragmented Low-Z Ion Beams for the NA61 Experiment at the CERN SPS

CERN Document Server

Efthymiopoulos, I; Bohl, T; Breuker, H; Calviani, M; Manglunki, D; Mataguez, S; Maury, S; Valderanis, C; Cornelis, K; Spanggaard, J; Cettour-Cave, S; Gazdzicki, M; Seyboth, P; Guber, F; Ivashkin, A

2011-01-01

The NA61 experiment, aims to study the properties of the onset of deconfinement at low SPS energies and to find signatures of the critical point of strongly interacting matter. A broad range in T-μB phase diagram will be covered by performing an energy (13A-158AGeV/c) and system size (p+p, Be+Be, Ar+Ca, Xe+La) scan. In a first phase, fragmented ion beams of 7Be or 11C produced as secondaries with the same momentum per nucleon when the incident primary Pb-ion beam hits a thin Be target will be used. The H2 beam line that transports the beam to the experiment acts as a double spectrometer which combined with a new thin target (degrader) where fragments loose energy proportional to the square of their charge allows the separation of the wanted A/Z fragments. Thin scintillators and TOF measurement for the low energy points are used as particle identification devices. In this paper results from the first test of the fragmented ion beam done in 2010 will be presented showing that a pure Be beam can be obtained sa...

Label free fragment screening using surface plasmon resonance as a tool for fragment finding - analyzing parkin, a difficult CNS target.

Directory of Open Access Journals (Sweden)

Karin Regnström

Full Text Available Surface Plasmon Resonance (SPR is rarely used as a primary High-throughput Screening (HTS tool in fragment-based approaches. With SPR instruments becoming increasingly high-throughput it is now possible to use SPR as a primary tool for fragment finding. SPR becomes, therefore, a valuable tool in the screening of difficult targets such as the ubiquitin E3 ligase Parkin. As a prerequisite for the screen, a large number of SPR tests were performed to characterize and validate the active form of Parkin. A set of compounds was designed and used to define optimal SPR assay conditions for this fragment screen. Using these conditions, more than 5000 pre-selected fragments from our in-house library were screened for binding to Parkin. Additionally, all fragments were simultaneously screened for binding to two off target proteins to exclude promiscuous binding compounds. A low hit rate was observed that is in line with hit rates usually obtained by other HTS screening assays. All hits were further tested in dose responses on the target protein by SPR for confirmation before channeling the hits into Nuclear Magnetic Resonance (NMR and other hit-confirmation assays.

Multi-target consensus circle pursuit for multi-agent systems via a distributed multi-flocking method

Science.gov (United States)

Pei, Huiqin; Chen, Shiming; Lai, Qiang

2016-12-01

This paper studies the multi-target consensus pursuit problem of multi-agent systems. For solving the problem, a distributed multi-flocking method is designed based on the partial information exchange, which is employed to realise the pursuit of multi-target and the uniform distribution of the number of pursuing agents with the dynamic target. Combining with the proposed circle formation control strategy, agents can adaptively choose the target to form the different circle formation groups accomplishing a multi-target pursuit. The speed state of pursuing agents in each group converges to the same value. A Lyapunov approach is utilised to analyse the stability of multi-agent systems. In addition, a sufficient condition is given for achieving the dynamic target consensus pursuit, and which is then analysed. Finally, simulation results verify the effectiveness of the proposed approaches.

Virtual Screening of Peptide and Peptidomimetic Fragments Targeted to Inhibit Bacterial Dithiol Oxidase DsbA.

Directory of Open Access Journals (Sweden)

Wilko Duprez

Full Text Available Antibacterial drugs with novel scaffolds and new mechanisms of action are desperately needed to address the growing problem of antibiotic resistance. The periplasmic oxidative folding system in Gram-negative bacteria represents a possible target for anti-virulence antibacterials. By targeting virulence rather than viability, development of resistance and side effects (through killing host native microbiota might be minimized. Here, we undertook the design of peptidomimetic inhibitors targeting the interaction between the two key enzymes of oxidative folding, DsbA and DsbB, with the ultimate goal of preventing virulence factor assembly. Structures of DsbB--or peptides--complexed with DsbA revealed key interactions with the DsbA active site cysteine, and with a hydrophobic groove adjacent to the active site. The present work aimed to discover peptidomimetics that target the hydrophobic groove to generate non-covalent DsbA inhibitors. The previously reported structure of a Proteus mirabilis DsbA active site cysteine mutant, in a non-covalent complex with the heptapeptide PWATCDS, was used as an in silico template for virtual screening of a peptidomimetic fragment library. The highest scoring fragment compound and nine derivatives were synthesized and evaluated for DsbA binding and inhibition. These experiments discovered peptidomimetic fragments with inhibitory activity at millimolar concentrations. Although only weakly potent relative to larger covalent peptide inhibitors that interact through the active site cysteine, these fragments offer new opportunities as templates to build non-covalent inhibitors. The results suggest that non-covalent peptidomimetics may need to interact with sites beyond the hydrophobic groove in order to produce potent DsbA inhibitors.

Assessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery.

Science.gov (United States)

Coutard, Bruno; Decroly, Etienne; Li, Changqing; Sharff, Andrew; Lescar, Julien; Bricogne, Gérard; Barral, Karine

2014-06-01

Seasonal and pandemic flaviviruses continue to be leading global health concerns. With the view to help drug discovery against Dengue virus (DENV), a fragment-based experimental approach was applied to identify small molecule ligands targeting two main components of the flavivirus replication complex: the NS3 helicase (Hel) and the NS5 mRNA methyltransferase (MTase) domains. A library of 500 drug-like fragments was first screened by thermal-shift assay (TSA) leading to the identification of 36 and 32 fragment hits binding Hel and MTase from DENV, respectively. In a second stage, we set up a fragment-based X-ray crystallographic screening (FBS-X) in order to provide both validated fragment hits and structural binding information. No fragment hit was confirmed for DENV Hel. In contrast, a total of seven fragments were identified as DENV MTase binders and structures of MTase-fragment hit complexes were solved at resolution at least 2.0Å or better. All fragment hits identified contain either a five- or six-membered aromatic ring or both, and three novel binding sites were located on the MTase. To further characterize the fragment hits identified by TSA and FBS-X, we performed enzymatic assays to assess their inhibition effect on the N7- and 2'-O-MTase enzymatic activities: five of these fragment hits inhibit at least one of the two activities with IC50 ranging from 180μM to 9mM. This work validates the FBS-X strategy for identifying new anti-flaviviral hits targeting MTase, while Hel might not be an amenable target for fragment-based drug discovery (FBDD). This approach proved to be a fast and efficient screening method for FBDD target validation and discovery of starting hits for the development of higher affinity molecules that bind to novel allosteric sites. Copyright © 2014 Elsevier B.V. All rights reserved.

PMHT Approach for Multi-Target Multi-Sensor Sonar Tracking in Clutter.

Science.gov (United States)

Li, Xiaohua; Li, Yaan; Yu, Jing; Chen, Xiao; Dai, Miao

2015-11-06

Multi-sensor sonar tracking has many advantages, such as the potential to reduce the overall measurement uncertainty and the possibility to hide the receiver. However, the use of multi-target multi-sensor sonar tracking is challenging because of the complexity of the underwater environment, especially the low target detection probability and extremely large number of false alarms caused by reverberation. In this work, to solve the problem of multi-target multi-sensor sonar tracking in the presence of clutter, a novel probabilistic multi-hypothesis tracker (PMHT) approach based on the extended Kalman filter (EKF) and unscented Kalman filter (UKF) is proposed. The PMHT can efficiently handle the unknown measurements-to-targets and measurements-to-transmitters data association ambiguity. The EKF and UKF are used to deal with the high degree of nonlinearity in the measurement model. The simulation results show that the proposed algorithm can improve the target tracking performance in a cluttered environment greatly, and its computational load is low.

High energy nuclear collisions in the few GeV/nucleon region: projectile and target fragmentation

International Nuclear Information System (INIS)

Schroeder, L.S.

1980-06-01

A general review of nucleon-nucleus and nucleus-nucleus collisions for incident energies <10 GeV/nucleon is presented. The division of these interactions into peripheral and central collisions is briefly discussed. Subjects treated include the following: target and projectile fragmentation systematics, production of exotic nuclear fragments, studies of multiparticle final states, total cross section measurements, results from an experiment that indicate the production of projectile fragments with an anomalously short reaction mean free path, high-energy particle production at backward angles beyond simple N-N kinematic limits, and recent results on backward particle emission in studies with the Berkeley streamer chamber. Both the particle and nuclear physics aspects that are present are considered. A brief discussion of future trends in this energy range ends the presentation. 65 references, 37 figures

The rise and fall of multi-fragment emission

International Nuclear Information System (INIS)

Ogilvie, C.A.; Begemann-Blaich, M.; Hubele, J.; Kunde, G.J.; Lindenstruth, V.; Liu, Z.; Lynen, U.; Meijer, R.J.; Milkau, U.; Mueller, W.F.J.; Sann, H.; Trautmann, W.; Adloff, J.C.; Rudolf, G.; Stuttge, L.

1991-03-01

We have studied multifragment decays of Au projectiles after collissions with C, Al, and Cu targets at a bombarding energy of 600 MeV/nucleon. We find that with increasing violence of the collision, measured via the associated multiplicity of light particles, the mean multiplicity of intermediate mass fragments first increases to a maximum IMF >≅3 and then decreases again. Calculations using the BUU model suggest that the fragmentation is governed by the energy E dep deposited into the Au nucleus and that IMF > reaches its maximum around E dep ≅8 MeV/nucleon. PACS 25.70 Np. (orig.)

Development of windowless liquid lithium targets for fragmentation and fission of 400-kW uranium beams

CERN Document Server

Nolen, J A; Hassanein, A; Novick, V J; Plotkin, P; Specht, J R

2003-01-01

The driver linac of the proposed rare isotope accelerator facility is designed to deliver 2x10 sup 1 sup 3 uranium ions per second at 400 MeV/u on target for radionuclide production via the fission and fragmentation mechanisms. The ion optics of the large acceptance, high-resolution fragment separators that follow the production target require primary beam spot widths of 1 mm. To cope with the resulting high power densities, windowless liquid lithium targets are being developed. The present designs build on existing experience with liquid lithium and liquid sodium systems that have been used for fusion and fission applications. However, no completely windowless systems have been developed or tested to date. For the beam power indicated above (400 kW), the flow requirements are up to about 20 m/s and 10 l/s linear and volume flow rates, respectively. The required target thickness is 1-1.5 g/cm sup 2 (2-3 cm lithium thickness). At this time a prototype windowless system with a lithium thickness of 1-2 cm is und...

Experiments on the nuclear fragmentation and on the production of radioactive beams for direct reactions

International Nuclear Information System (INIS)

Weiss, A.

1993-06-01

In April 1992 at the GSI a prototype experiment on the production and study of the double-magic radioactive nucleus 56 Ni was successfully performed with proton scattering in inverse kinematics. A 350 MeV/u 56 Ni primary beam from the heavy ion synchrotron SIS was fragmented in a 4/g/cm 2 thick beryllium target. The separation of the formed isotopes ensued in the fragment separator FRS, which was operated in the achromatic mode with a degrader. Production cross sections for a whole series of fragments in the range 29≥Z≥19 and 57≥A≥41 were obtained. It succeeded to detect proton-rich isotopes at the boundary of the stability as for instance 52 Co, 51 Co, 50 Co, or 52 Ni and to determine for the first time their production cross sections. A further part of this thesis with regard to experiments with radioactive beams were first test experiments at the experimental storage ring ESR. The spotlight held luminosity measurements at the internal gas target with cooled, stable proton beam. For this the elastic scattering was stuided in inverse kinematics in the Rutherford range. Studied were different projectile beams (Ne, Xe) at energies of 150 MeV/u respectively 250 MeV/u and gas jets of nitrogen, argon, and hydrogen. The measured energy spectra of the recoils are in agreement with simulation calculations

Molten aluminum alloy fuel fragmentation experiments

International Nuclear Information System (INIS)

Gabor, J.D.; Purviance, R.T.; Cassulo, J.C.; Spencer, B.W.

1992-01-01

Experiments were conducted in which molten aluminum alloys were injected into a 1.2 m deep pool of water. The parameters varied were (i) injectant material (8001 aluminum alloy and 12.3 wt% U-87.7 wt% Al), (ii) melt superheat (O to 50 K), (iii) water temperature (313, 343 and 373 K) and (iv) size and geometry of the pour stream (5, 10 and 20 mm diameter circular and 57 mm annular). The pour stream fragmentation was dominated by surface tension with large particles (∼30 mm) being formed from varicose wave breakup of the 10-mm circular pours and from the annular flow off a 57 mm diameter tube. The fragments produced by the 5 mm circular et were smaller (∼ mm), and the 20 mm jet which underwent sinuous wave breakup produced ∼100 mm fragments. The fragments froze to form solid particles in 313 K water, and when the water was ≥343 K, the melt fragments did not freeze during their transit through 1.2 m of water

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

Science.gov (United States)

Dias, David M; Ciulli, Alessio

2014-01-01

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

12C fragmentation at 95 MeV per nucleon for hadron-therapy. Experimental study and simulation with thick PMMA targets

International Nuclear Information System (INIS)

Braunn, B.

2010-11-01

A study of the 12 C fragmentation at 95 MeV per nucleon on thick PMMA targets is presented on this document. This study is motivated by the development of a new technique for irradiation of malignant tumours: the carbon ion therapy. The purpose of this work is to compare experimental data against nuclear models used in GEANT4 tool-kit. The aim is to determine if the models are sufficiently predictive to the criteria of hadron-therapy. To achieve this goal, a first experiment was performed at GANIL with a 12 C beam at 95 MeV/u and thick PMMA targets. This experiment has achieved the production rates, angular and energy distributions of different fragments produced in nuclear collisions. Comparisons between experimental data and simulated results obtained using the binary intra-nuclear cascade (BIC) and quantum molecular dynamics model (QMD) available in GEANT4 have been performed. These comparisons show the inability of the tested models to reproduce carbon fragmentation at 95 MeV per nucleon with the accuracy required in hadron-therapy. (author)

Multi-fragmentation of C{sub 60} induced by {sup 4}He{sup 2+} impact (E<60 keV/amu) and investigated by a multi-correlation technique

Energy Technology Data Exchange (ETDEWEB)

Rentenier, A.; Moretto-Capelle, P. E-mail: pmc@irsamc.ups-tlse.fr; Bordenave-Montesquieu, D.; Bordenave-Montesquieu, A

2003-05-01

In this communication, the C{sub 60} multi-fragmentation induced by {sup 4}He{sup 2+} ion impact in the 20-240 keV energy range, is investigated. Using a multi-stop time-of-flight technique, it becomes possible to measure partial spectra corresponding to the simultaneous emission of 2-5 light charged fragments; small charged fragments are found to be accompanied by the emission of at least another one. The fragment size distribution depends on the collisional energy and the multiplicity of emitted charged fragments. It is more peaked on small sizes when the collision velocity or the multiplicity increases. Corresponding relative cross sections are also measured; processes with emission of 2 and 3 charged fragments are always dominant but their relative weights decrease slowly when the collision energy increases.

Target Immobilization as a Strategy for NMR-Based Fragment Screening: Comparison of TINS, STD, and SPR for Fragment Hit Identification

NARCIS (Netherlands)

Kobayashi, M.; Retra, K.; Figaroa, F.; Hollander, J.G.; Ab, E.; Heetebrij, R.J.; Irth, H.; Siegal, G.

2010-01-01

Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the

Integration of fragment screening and library design.

Science.gov (United States)

Siegal, Gregg; Ab, Eiso; Schultz, Jan

2007-12-01

With more than 10 years of practical experience and theoretical analysis, fragment-based drug discovery (FBDD) has entered the mainstream of the pharmaceutical and biotech industries. An array of biophysical techniques has been used to detect the weak interaction between a fragment and the target. Each technique presents its own requirements regarding the fragment collection and the target; therefore, in order to optimize the potential of FBDD, the nature of the target should be a driving factor for simultaneous development of both the library and the screening technology. A roadmap is now available to guide fragment-to-lead evolution when structural information is available. The next challenge is to apply FBDD to targets for which high-resolution structural information is not available.

SAR Target Recognition Based on Multi-feature Multiple Representation Classifier Fusion

Directory of Open Access Journals (Sweden)

Zhang Xinzheng

2017-10-01

Full Text Available In this paper, we present a Synthetic Aperture Radar (SAR image target recognition algorithm based on multi-feature multiple representation learning classifier fusion. First, it extracts three features from the SAR images, namely principal component analysis, wavelet transform, and Two-Dimensional Slice Zernike Moments (2DSZM features. Second, we harness the sparse representation classifier and the cooperative representation classifier with the above-mentioned features to get six predictive labels. Finally, we adopt classifier fusion to obtain the final recognition decision. We researched three different classifier fusion algorithms in our experiments, and the results demonstrate thatusing Bayesian decision fusion gives thebest recognition performance. The method based on multi-feature multiple representation learning classifier fusion integrates the discrimination of multi-features and combines the sparse and cooperative representation classification performance to gain complementary advantages and to improve recognition accuracy. The experiments are based on the Moving and Stationary Target Acquisition and Recognition (MSTAR database,and they demonstrate the effectiveness of the proposed approach.

Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

Science.gov (United States)

Lau, Wan F.; Withka, Jane M.; Hepworth, David; Magee, Thomas V.; Du, Yuhua J.; Bakken, Gregory A.; Miller, Michael D.; Hendsch, Zachary S.; Thanabal, Venkataraman; Kolodziej, Steve A.; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S.; Love, Robert; Charlton, Maura E.; Hughes, Samantha; van Hoorn, Willem P.; Mills, James E.

2011-07-01

Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR, FB-QSSR, multi objective (MO-QSPR) and MIF studies.

Science.gov (United States)

Manoharan, Prabu; Vijayan, R S K; Ghoshal, Nanda

2010-10-01

The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables (X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors.

Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR, FB-QSSR, multi objective (MO-QSPR) and MIF studies

Science.gov (United States)

Manoharan, Prabu; Vijayan, R. S. K.; Ghoshal, Nanda

2010-10-01

The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables ( X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors.

Nuclear targeting by fragmentation of the Potato spindle tuber viroid genome

International Nuclear Information System (INIS)

Abraitiene, Asta; Zhao Yan; Hammond, Rosemarie

2008-01-01

Transient expression of engineered reporter RNAs encoding an intron-containing green fluorescent protein (GFP) from a Potato virus X-based expression vector previously demonstrated the nuclear targeting capability of the 359 nucleotide Potato spindle tuber viroid (PSTVd) RNA genome. To further delimit the putative nuclear-targeting signal, PSTVd subgenomic fragments were embedded within the intron, and recombinant reporter RNAs were inoculated onto Nicotiana benthamiana plants. Appearance of green fluorescence in leaf tissue inoculated with PSTVd-fragment-containing constructs indicated shuttling of the RNA into the nucleus by fragments as short as 80 nucleotides in length. Plant-to-plant variation in the timing of intron removal and subsequent GFP fluorescence was observed; however, earliest and most abundant GFP expression was obtained with constructs containing the conserved hairpin I palindrome structure and embedded upper central conserved region. Our results suggest that this conserved sequence and/or the stem-loop structure it forms is sufficient for import of PSTVd into the nucleus

The OPERA experiment Target Tracker

CERN Document Server

Adam, T; Borer, K.; Campagne, Jean-Eric; Con-Sen, N.; de La Taille, C.; Dick, N.; Dracos, M.; Gaudiot, G.; Goeltzenlichter, T.; Gornushkin, Y.; Grapton, J.-N.; Guyonnet, J.-L.; Hess, M.; Igersheim, R.; Janicsko Csathy, J.; Jollet, C.; Juget, F.; Kocher, H.; Krasnoperov, A.; Krumstein, Z.; Martin-Chassard, G.; Moser, U.; Nozdrin, A.; Olchevski, A.; Porokhovoi, S.; Raux, L.; Sadovski, A.; Schuler, J.; Schutz, H.-U.; Schwab, C.; Smolnikov, A.; Van Beek, G.; Vilain, P.; Walchli, T.; Wilquet, G.; Wurtz, J.

2007-01-01

The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described.

Real-Time Multi-Target Localization from Unmanned Aerial Vehicles

Directory of Open Access Journals (Sweden)

Xuan Wang

2016-12-01

Full Text Available In order to improve the reconnaissance efficiency of unmanned aerial vehicle (UAV electro-optical stabilized imaging systems, a real-time multi-target localization scheme based on an UAV electro-optical stabilized imaging system is proposed. First, a target location model is studied. Then, the geodetic coordinates of multi-targets are calculated using the homogeneous coordinate transformation. On the basis of this, two methods which can improve the accuracy of the multi-target localization are proposed: (1 the real-time zoom lens distortion correction method; (2 a recursive least squares (RLS filtering method based on UAV dead reckoning. The multi-target localization error model is established using Monte Carlo theory. In an actual flight, the UAV flight altitude is 1140 m. The multi-target localization results are within the range of allowable error. After we use a lens distortion correction method in a single image, the circular error probability (CEP of the multi-target localization is reduced by 7%, and 50 targets can be located at the same time. The RLS algorithm can adaptively estimate the location data based on multiple images. Compared with multi-target localization based on a single image, CEP of the multi-target localization using RLS is reduced by 25%. The proposed method can be implemented on a small circuit board to operate in real time. This research is expected to significantly benefit small UAVs which need multi-target geo-location functions.

Spin and diffractive physics with a fixed-target experiment at the LHC (AFTER-LHC)

Energy Technology Data Exchange (ETDEWEB)

Lorce, C.; Chambert, V.; Didelez, J. P.; Genolini, B.; Hadjidakis, C.; Lansberg, J. P.; Rosier, P. [IPNO, Universite Paris-Sud, CNRS/IN2P3, F-91406, Orsay (France); Anselmino, M.; Arnaldi, R.; Scomparin, E. [INFN Sez. Torino, Via P. Giuria 1,1-10125, Torino (Italy); Brodsky, S. J. [SLAC National Accelerator Laboratory, Stanford U, Stanford, CA 94309, (United States); Ferreiro, E. G. [Departamento de Fisica de Particulas, Univ. de Santiago de C, 15782 Santiago de C (Spain); Fleuret, F. [Laboratoire Leprince Ringuet, Ecole Polytechnique, CNRS/IN2P3, 91128 Palaiseau (France); Rakotozafindrabe, A. [IRFU/SPhN, CFA Society, 91191 Gifsur-Yvette Cedex (France); Schienbein, I. [LPSC, Universite Joseph Fourier, CNRS/IN2P3/INPG, F-38026 Grenoble (France); Uggerhoj, U. I. [Department of Physics and Astronomy, University of Aarhus (Denmark)

2013-04-15

We report on the spin and diffractive physics at a future multi-purpose f xed-target experiment with proton and lead LHC beams extracted by a bent crystal. The LHC multi-TeV beams allow for the most energetic f xed-target experiments ever performed, opening new domains of particle and nuclear physics and complementing that of collider physics, in particular that of RHIC and the EIC projects. The luminosity achievable with AFTER using typical targets would surpass that of RHIC by more than 3 orders of magnitude. The f xed-target mode has the advantage to allow for measurements of single-spin asymmetries with polarized target as well as of single-diffractive processes in the target region.

Spin and diffractive physics with a fixed-target experiment at the LHC (AFTER-LHC)

International Nuclear Information System (INIS)

Lorcé, C.; Chambert, V.; Didelez, J. P.; Genolini, B.; Hadjidakis, C.; Lansberg, J. P.; Rosier, P.; Anselmino, M.; Arnaldi, R.; Scomparin, E.; Brodsky, S. J.; Ferreiro, E. G.; Fleuret, F.; Rakotozafindrabe, A.; Schienbein, I.; Uggerhøj, U. I.

2013-01-01

We report on the spin and diffractive physics at a future multi-purpose f xed-target experiment with proton and lead LHC beams extracted by a bent crystal. The LHC multi-TeV beams allow for the most energetic f xed-target experiments ever performed, opening new domains of particle and nuclear physics and complementing that of collider physics, in particular that of RHIC and the EIC projects. The luminosity achievable with AFTER using typical targets would surpass that of RHIC by more than 3 orders of magnitude. The f xed-target mode has the advantage to allow for measurements of single-spin asymmetries with polarized target as well as of single-diffractive processes in the target region.

Origin of fragments in multifragmentation reactions

International Nuclear Information System (INIS)

Zbiri, K.; Aichelin, J.

2005-01-01

Using the quantum molecular dynamics approach we have started to analyze the results of the recent INDRA experiments at GSI experiments. For the first time we could identify a midrapidity source in which fragments are formed from a almost identical fraction of projectile and target nucleons. In smaller systems we have not found this source. Nevertheless the fragment spectra at small and large angles are completely determined by the dynamics. We discuss how fragments are formed in the different regions of phase space and what they tell us about the reaction mechanism. (author)

Fragment approaches in structure-based drug discovery

International Nuclear Information System (INIS)

Hubbard, Roderick E.

2008-01-01

Fragment-based methods are successfully generating novel and selective drug-like inhibitors of protein targets, with a number of groups reporting compounds entering clinical trials. This paper summarizes the key features of the approach as one of the tools in structure-guided drug discovery. There has been considerable interest recently in what is known as 'fragment-based lead discovery'. The novel feature of the approach is to begin with small low-affinity compounds. The main advantage is that a larger potential chemical diversity can be sampled with fewer compounds, which is particularly important for new target classes. The approach relies on careful design of the fragment library, a method that can detect binding of the fragment to the protein target, determination of the structure of the fragment bound to the target, and the conventional use of structural information to guide compound optimization. In this article the methods are reviewed, and experiences in fragment-based discovery of lead series of compounds against kinases such as PDK1 and ATPases such as Hsp90 are discussed. The examples illustrate some of the key benefits and issues of the approach and also provide anecdotal examples of the patterns seen in selectivity and the binding mode of fragments across different protein targets

A collagen-binding EGFR antibody fragment targeting tumors with a collagen-rich extracellular matrix

OpenAIRE

Hui Liang; Xiaoran Li; Bin Wang; Bing Chen; Yannan Zhao; Jie Sun; Yan Zhuang; Jiajia Shi; He Shen; Zhijun Zhang; Jianwu Dai

2016-01-01

Many tumors over-express collagen, which constitutes the physical scaffold of tumor microenvironment. Collagen has been considered to be a target for cancer therapy. The collagen-binding domain (CBD) is a short peptide, which could bind to collagen and achieve the sustained release of CBD-fused proteins in collagen scaffold. Here, a collagen-binding EGFR antibody fragment was designed and expressed for targeting the collagen-rich extracellular matrix in tumors. The antibody fragment (Fab) of ...

Nuclear-breakup mechanisms in the interaction of relativistic projectiles with heavy targets

International Nuclear Information System (INIS)

Steinberg, E.P.

1982-01-01

The breakup of a Au nucleus under bombardment with relativistic p, α, and 20 Ne has been investigated in an extensive, multi-detector study. The present discussion addresses some of the many aspects of the experimental results. A broad distribution of coincident fragment masses is observed, with the total fragment kinetic energy being higher than expected for a fission mechanism for total fragment mass less than or equal to 120. The formation of light fragments is shown to be inconsistent with a binary breakup mechanism, and a multi-fragment target breakup is suggested. In general, the results indicate a broad spectrum of violence in the collisions, from gentle, leading to the production of heavy spallation products and fission, to essentially explosive, leading to multi-fragment breakup into light mas products. These aspects of the reactions represent a late-stage breakup of the target residues and are positively correlated with the violence of the initial fast stage of the collision as measured by the charged particle multiplicity

Uranium target fragmentation by intermediate and high energy 12C and 20Ne ions

International Nuclear Information System (INIS)

McGaughey, P.L.; Loveland, W.; Morrissey, D.J.; Aleklett, K.; Seaborg, G.T.

1985-01-01

Target fragment formation cross sections for nuclides with 24 12 C and 8.0 and 20.0 GeV 20 Ne with 238 U. Fragment isobaric yields were deduced from these data. The light fragment (A 12 C projectile energy of 1.0 GeV, the n-deficient fragments appear to originate primarily from a fission rather than a spallation process.) The excitation functions of the heavy fragments with 60 60, indicating that the general pattern of yields of these fragments is governed by the excitation energy deposited in the nucleus during the first step of the reaction and the geometry of the collision

Multi-target molecular imaging and its progress in research and application

International Nuclear Information System (INIS)

Tang Ganghua

2011-01-01

Multi-target molecular imaging (MMI) is an important field of research in molecular imaging. It includes multi-tracer multi-target molecular imaging(MTMI), fusion-molecule multi-target imaging (FMMI), coupling-molecule multi-target imaging (CMMI), and multi-target multifunctional molecular imaging(MMMI). In this paper,imaging modes of MMI are reviewed, and potential applications of positron emission tomography MMI in near future are discussed. (author)

Fragmentation in peripheral heavy-ion collisions: from neck emission to spectator decays

Energy Technology Data Exchange (ETDEWEB)

Lukasik, J.; Auger, G.; Begemann-Blaich, M.L.; Bellaize, N.; Bittiger, R.; Bocage, F.; Borderie, B.; Bougault, R.; Bouriquet, B.; Charvet, J.L.; Chbihi, A.; Dayras, R.; Durand, D.; Frankland, J.D.; Galichet, E.; Gourio, D.; Guinet, D.; Hudan, S.; Hurst, B.; Lautesse, P.; Lavaud, F.; Le Fevre, A.; Legrain, R.; Lopez, O.; Lynen, U.; Mueller, W.F.J.; Nalpas, L.; Orth, H.; Plagnol, E.; Rosato, E.; Saija, A.; Schwarz, C.; Sfienti, C.; Steckmeyer, J.C.; Tamain, B.; Trautmann, W.; Trzcinski, A.; Turzo, K.; Vient, E.; Vigilante, M.; Volant, C.; Zwieglinski, B.; Botvina, A.S

2003-07-24

Invariant cross sections of intermediate mass fragments in peripheral collisions of {sup 197}Au on {sup 197}Au at incident energies between 40 and 150 MeV per nucleon have been measured with the 4{pi} multi-detector INDRA. The maximum of the fragment production is located near mid-rapidity at the lower energies and moves gradually towards the projectile and target rapidities as the energy is increased. Schematic calculations within an extended Goldhaber model suggest that the observed cross section distributions and their evolution with energy are predominantly the result of the clustering requirement for the emerging fragments and of their Coulomb repulsion from the projectile and target residues. The quantitative comparison with transverse energy spectra and fragment charge distributions emphasizes the role of hard scattered nucleons in the fragmentation process.

Fragmentation of relativistic nuclei

International Nuclear Information System (INIS)

Cork, B.

1975-06-01

Nuclei with energies of several GeV/n interact with hadrons and produce fragments that encompass the fields of nuclear physics, meson physics, and particle physics. Experimental results are now available to explore problems in nuclear physics such as the validity of the shell model to explain the momentum distribution of fragments, the contribution of giant dipole resonances to fragment production cross sections, the effective Coulomb barrier, and nuclear temperatures. A new approach to meson physics is possible by exploring the nucleon charge-exchange process. Particle physics problems are explored by measuring the energy and target dependence of isotope production cross sections, thus determining if limiting fragmentation and target factorization are valid, and measuring total cross sections to determine if the factorization relation, sigma/sub AB/ 2 = sigma/sub AA/ . sigma/sub BB/, is violated. Also, new experiments have been done to measure the angular distribution of fragments that could be explained as nuclear shock waves, and to explore for ultradense matter produced by very heavy ions incident on heavy atoms. (12 figures, 2 tables)

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

Science.gov (United States)

2018-01-01

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain. PMID:29436819

Uranium target fragmentation by intermediate and high energy 12C and 20Ne

International Nuclear Information System (INIS)

McGaughey, P.L.; Loveland, W.; Morrissey, D.J.; Aleklett, K.; Seaborg, G.T.

1985-01-01

The authors report herein the final analysis of the measurement of the target fragment production cross sections for nuclides with 24 less than or equal to A less than or equal to 237 from the interaction of 1.0, 3.0, 4.8, and 12 GeV 12 C and 8.0 and 20.0 GeV 20 Ne with 238 U. Isobaric yield distributions deduced from the nuclidic formation cross sections along with predictions of these distributions made using the nuclear firestreak and intranuclear cascade models are shown. Contrary to a previous report no large yields of fragments with 160 less than or equal to A less than or equal to 200 are observed in any reaction. Both the intranuclear cascade model and the nuclear firestreak model satisfactorily predict the observed yields of fragments with A > 60 indicating the general pattern of yields of these fragments is governed by the excitation energy deposited in the nucleus during the initial projectile-target interaction and the geometry of the collision

Fragment-based approaches to the discovery of kinase inhibitors.

Science.gov (United States)

Mortenson, Paul N; Berdini, Valerio; O'Reilly, Marc

2014-01-01

Protein kinases are one of the most important families of drug targets, and aberrant kinase activity has been linked to a large number of disease areas. Although eminently targetable using small molecules, kinases present a number of challenges as drug targets, not least obtaining selectivity across such a large and relatively closely related target family. Fragment-based drug discovery involves screening simple, low-molecular weight compounds to generate initial hits against a target. These hits are then optimized to more potent compounds via medicinal chemistry, usually facilitated by structural biology. Here, we will present a number of recent examples of fragment-based approaches to the discovery of kinase inhibitors, detailing the construction of fragment-screening libraries, the identification and validation of fragment hits, and their optimization into potent and selective lead compounds. The advantages of fragment-based methodologies will be discussed, along with some of the challenges associated with using this route. Finally, we will present a number of key lessons derived both from our own experience running fragment screens against kinases and from a large number of published studies.

Target conception for the Munich fission fragment accelerator

CERN Document Server

Maier, H J; Gross, M L; Grossmann, R; Kester, O; Thirolf, P

1999-01-01

For the new high-flux reactor FRM II, the fission fragment accelerator MAFF is under design. MAFF will supply intense mass-separated radioactive ion beams of very neutron-rich nuclei with energies around the Coulomb barrier. A central part of this accelerator is the ion source with the fission target, which is operated at a neutron flux of 1.5x10 sup 1 sup 4 cm sup - sup 2 s sup - sup 1. The target consists of typically 1 g of sup 2 sup 3 sup 5 U dispersed in a cylindrical graphite matrix, which is encapsulated in a Re container. To enable diffusion and extraction of the fission products, the target has to be maintained at a temperature of up to 2400 deg. C during operation. It has to stand this temperature for at least one reactor cycle of 1250 h. Comprehensive tests are required to study the long-term behaviour of the involved materials at these conditions prior to operation in the reactor. The present paper gives details of the target conception and the projected tests.

Dynamic Failure and Fragmentation of a Hot-Pressed Boron Carbide

Science.gov (United States)

Sano, Tomoko; Vargas-Gonzalez, Lionel; LaSalvia, Jerry; Hogan, James David

2017-12-01

This study investigates the failure and fragmentation of a hot-pressed boron carbide during high rate impact experiments. Four impact experiments are performed using a composite-backed target configuration at similar velocities, where two of the impact experiments resulted in complete target penetration and two resulted in partial penetration. This paper seeks to evaluate and understand the dynamic behavior of the ceramic that led to either the complete or partial penetration cases, focusing on: (1) surface and internal failure features of fragments using optical, scanning electron, and transmission electron microscopy, and (2) fragment size analysis using state-of-the-art particle-sizing technology that informs about the consequences of failure. Detailed characterization of the mechanical properties and the microstructure is also performed. Results indicate that transgranular fracture was the primary mode of failure in this boron carbide material, and no stress-induced amorphization features were observed. Analysis of the fragment sizes for the partial and completely penetrated experiments revealed a possible correlation between larger fragment sizes and impact performance. The results will add insight into designing improved advanced ceramics for impact protection applications.

Looking for bimodal distributions in multi-fragmentation reactions

International Nuclear Information System (INIS)

Gulminelli, F.

2007-01-01

The presence of a phase transition in a finite system can be deduced, together with its order, from the form of the distribution of the order parameter. This issue has been extensively studied in multifragmentation experiments, with results that do not appear fully consistent. In this paper we discuss the effect of the statistical ensemble or sorting conditions on the form of fragment distributions, and propose a new method, which can be easily implemented experimentally, to discriminate between different fragmentation scenarios. This method, based on a re-weighting of the measured distribution to account for the experimental constraints linked to the energy deposit, is tested on different simple models, and appears to provide a powerful discrimination. (author)

Study of Target Fragmentation in the Interaction of 86 MeV/A $^{12}$Carbon with Tantalum, Bismuth and Uranium

CERN Multimedia

2002-01-01

Using radiochemical techniques we will ; a)~~measure the target fragment mass and charge distributions from the interaction of 86~MeV/A |1|2C with Ta, Bi and U; ; b)~~measure the target fragment forward momentum and average kinetic energy using the thick target-thick catcher technique for the above reactions; and ; c)~~measure the target fragment angular and differential energy distributions using thin target-thin catcher techniques for the reactions with Ta and U. \\\\ \\\\ These measurements should allow us to better characterize the transition between low energy and realistic heavy ion reaction mechanisms.

Total fragmentation cross section of 158A GeV lead projectiles in Cu target

International Nuclear Information System (INIS)

Mukhtar Ahmed Rana; Shahid Manzoor

2008-01-01

Total fragmentation cross section for the reaction 158A Pb ions + Cu target is measured using the most sensitive track detector CR-39. Measured values are compared with calculations. Exposures of target-detector stack with 158A Pb projectiles are made at CERN-SPS beam facility. Results of calibration of CR-39 detector in a charge region (63≤Z≤83) are also reported, which can be used for high energy particle identification using CR-39 and in determination of partial charge changing cross sections. The charge resolution σ Z achieved by this technique is about 0.2e. A systematic dependence of total fragmentation cross section on target properties is revealed and the corresponding results are presented. (authors)

Fragment-based drug discovery and its application to challenging drug targets.

Science.gov (United States)

Price, Amanda J; Howard, Steven; Cons, Benjamin D

2017-11-08

Fragment-based drug discovery (FBDD) is a technique for identifying low molecular weight chemical starting points for drug discovery. Since its inception 20 years ago, FBDD has grown in popularity to the point where it is now an established technique in industry and academia. The approach involves the biophysical screening of proteins against collections of low molecular weight compounds (fragments). Although fragments bind to proteins with relatively low affinity, they form efficient, high quality binding interactions with the protein architecture as they have to overcome a significant entropy barrier to bind. Of the biophysical methods available for fragment screening, X-ray protein crystallography is one of the most sensitive and least prone to false positives. It also provides detailed structural information of the protein-fragment complex at the atomic level. Fragment-based screening using X-ray crystallography is therefore an efficient method for identifying binding hotspots on proteins, which can then be exploited by chemists and biologists for the discovery of new drugs. The use of FBDD is illustrated here with a recently published case study of a drug discovery programme targeting the challenging protein-protein interaction Kelch-like ECH-associated protein 1:nuclear factor erythroid 2-related factor 2. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Multi-Robot, Multi-Target Particle Swarm Optimization Search in Noisy Wireless Environments

Energy Technology Data Exchange (ETDEWEB)

Kurt Derr; Milos Manic

2009-05-01

Multiple small robots (swarms) can work together using Particle Swarm Optimization (PSO) to perform tasks that are difficult or impossible for a single robot to accomplish. The problem considered in this paper is exploration of an unknown environment with the goal of finding a target(s) at an unknown location(s) using multiple small mobile robots. This work demonstrates the use of a distributed PSO algorithm with a novel adaptive RSS weighting factor to guide robots for locating target(s) in high risk environments. The approach was developed and analyzed on multiple robot single and multiple target search. The approach was further enhanced by the multi-robot-multi-target search in noisy environments. The experimental results demonstrated how the availability of radio frequency signal can significantly affect robot search time to reach a target.

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

Science.gov (United States)

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.

Targeted habitat restoration can reduce extinction rates in fragmented forests.

Science.gov (United States)

Newmark, William D; Jenkins, Clinton N; Pimm, Stuart L; McNeally, Phoebe B; Halley, John M

2017-09-05

The Eastern Arc Mountains of Tanzania and the Atlantic Forest of Brazil are two of the most fragmented biodiversity hotspots. Species-area relationships predict that their habitat fragments will experience a substantial loss of species. Most of these extinctions will occur over an extended time, and therefore, reconnecting fragments could prevent species losses and allow locally extinct species to recolonize former habitats. An empirical relaxation half-life vs. area relationship for tropical bird communities estimates the time that it takes to lose one-half of all species that will be eventually lost. We use it to estimate the increase in species persistence by regenerating a forest connection 1 km in width among the largest and closest fragments at 11 locations. In the Eastern Arc Mountains, regenerating 8,134 ha of forest would create >316,000 ha in total of restored contiguous forest. More importantly, it would increase the persistence time for species by a factor of 6.8 per location or ∼2,272 years, on average, relative to individual fragments. In the Atlantic Forest, regenerating 6,452 ha of forest would create >251,000 ha in total of restored contiguous forest and enhance species persistence by a factor of 13.0 per location or ∼5,102 years, on average, relative to individual fragments. Rapidly regenerating forest among fragments is important, because mean time to the first determined extinction across all fragments is 7 years. We estimate the cost of forest regeneration at $21-$49 million dollars. It could provide one of the highest returns on investment for biodiversity conservation worldwide.

Optical smoothing of laser imprinting in planar-target experiments on OMEGA EP using multi-FM 1-D smoothing by spectral dispersion

Energy Technology Data Exchange (ETDEWEB)

Hohenberger, M., E-mail: mhoh@lle.rochester.edu; Shvydky, A.; Marozas, J. A.; Bonino, M. J.; Canning, D.; Collins, T. J. B.; Dorrer, C.; Kessler, T. J.; Kruschwitz, B. E.; McKenty, P. W.; Regan, S. P.; Sangster, T. C.; Zuegel, J. D. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road Rochester, Rochester, New York 14623 (United States); Fiksel, G. [Nuclear Engineering and Radiological Sciences (NERS), University of Michigan, Ann Arbor, Michigan 48109 (United States); Meyerhofer, D. D. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

2016-09-15

Direct-drive ignition on the National Ignition Facility (NIF) requires single-beam smoothing to minimize imprinting of laser nonuniformities that can negatively affect implosion performance. One-dimensional, multi-FM smoothing by spectral dispersion (SSD) has been proposed to provide the required smoothing [Marozas et al., Bull. Am. Phys. Soc. 55, 294 (2010)]. A prototype multi-FM SSD system has been integrated into the NIF-like beamline of the OMEGA EP Laser System. Experiments have been performed to verify the smoothing performance by measuring Rayleigh–Taylor growth rates in planar targets of laser-imprinted and preimposed surface modulations. Multi-FM 1-D SSD has been observed to reduce imprint levels by ∼50% compared to the nominal OMEGA EP SSD system. The experimental results are in agreement with 2-D DRACO simulations using realistic, time-dependent far-field spot-intensity calculations that emulate the effect of SSD.

Bose-Einstein correlations in the target fragmentation region in 200A GeV 16O + nucleus collisions

International Nuclear Information System (INIS)

Albrecht, R.; Bock, R.; Gutbrod, H.H.; Kolb, B.W.; Lund, I.; Schmidt, H.R.; Awes, T.C.; Ferguson, R.L.; Franz, A.; Obenshain, F.E.; Plasil, F.; Saini, S.; Soerensen, S.P.; Tincknell, M.L.; Young, G.R.; Beckmann, P.; Berger, F.; Bock, D.; Clewing, G.; Dragon, L.; Glasow, R.; Hartig, M.; Hoelker, G.; Kampert, K.H.; Loehner, H.; Peitzmann, T.; Purschke, M.; Roters, B.; Santo, R.; Schmidt, R.; Steffens, K.; Steinhaeuser, P.; Stueken, D.; Twyhues, A.; Bloomer, M.A.; Jacobs, P.; Poskanzer, A.M.; Ritter, H.G.; Claesson, G.; Eklund, A.; Garpman, S.; Gustafsson, H.A.; Idh, J.; Kristiansson, P.; Oskarsson, A.; Otterlund, I.; Persson, S.; Stenlund, E.

1992-01-01

Correlations between positive pions are investigated in the target fragmentation region of 200 A GeV 16 O+nucleus collisions. The pions are measured with the Plastic Ball detector in the WA80 experiment at the CERN SPS. The target mass dependence of the radii and the correlation strength extracted by interferometry is studied. A new approach to the fit of the correlation functions is introduced. The correlation strength and both invariant and transverse radii increase with decreasing target mass. The transverse radius for 16 O+C reactions appears to be much larger than the geometrical radius of the nuclei involved. For the Au target only a small fraction of the measured pions contributes to the apparent correlation. Hints for a much larger second component in 16 O+Au reactions are observed. Rescattering phenomena may provide a clue to understand these phenomena. (orig.)

A Bioinorganic Approach to Fragment-Based Drug Discovery Targeting Metalloenzymes.

Science.gov (United States)

Cohen, Seth M

2017-08-15

Metal-dependent enzymes (i.e., metalloenzymes) make up a large fraction of all enzymes and are critically important in a wide range of biological processes, including DNA modification, protein homeostasis, antibiotic resistance, and many others. Consequently, metalloenzymes represent a vast and largely untapped space for drug development. The discovery of effective therapeutics that target metalloenzymes lies squarely at the interface of bioinorganic and medicinal chemistry and requires expertise, methods, and strategies from both fields to mount an effective campaign. In this Account, our research program that brings together the principles and methods of bioinorganic and medicinal chemistry are described, in an effort to bridge the gap between these fields and address an important class of medicinal targets. Fragment-based drug discovery (FBDD) is an important drug discovery approach that is particularly well suited for metalloenzyme inhibitor development. FBDD uses relatively small but diverse chemical structures that allow for the assembly of privileged molecular collections that focus on a specific feature of the target enzyme. For metalloenzyme inhibition, the specific feature is rather obvious, namely, a metal-dependent active site. Surprisingly, prior to our work, the exploration of diverse molecular fragments for binding the metal active sites of metalloenzymes was largely unexplored. By assembling a modest library of metal-binding pharmacophores (MBPs), we have been able to find lead hits for many metalloenzymes and, from these hits, develop inhibitors that act via novel mechanisms of action. A specific case study on the use of this strategy to identify a first-in-class inhibitor of zinc-dependent Rpn11 (a component of the proteasome) is highlighted. The application of FBDD for the development of metalloenzyme inhibitors has raised several other compelling questions, such as how the metalloenzyme active site influences the coordination chemistry of bound

Total Fragmentation Cross Section of 158A GeV Lead Projectiles in Cu Target

International Nuclear Information System (INIS)

Rana, Mukhtar Ahmed

2008-01-01

Total fragmentation cross section for the reaction 158 A Pb ions + Cu target is measured using the most sensitive track detector CR-39. Measured values are compared with calculations. Exposures of target-detector stack with 158A Pb projectiles are made at CERN-SPS beam facility. Results of calibration of CR-39 detector in a charge region (63 ≤ Z ≤ 83) are also reported, which can be used for high energy particle identification using CR-39 and in determination of partial charge changing cross sections. The charge resolution σ z achieved by this technique is about 0.2e. A systematic dependence of total fragmentation cross section on target properties is revealed and the corresponding results are presented. (nuclear physics)

Using In Silico Fragmentation to Improve Routine Residue Screening in Complex Matrices

Science.gov (United States)

Kaufmann, Anton; Butcher, Patrick; Maden, Kathryn; Walker, Stephan; Widmer, Mirjam

2017-12-01

Targeted residue screening requires the use of reference substances in order to identify potential residues. This becomes a difficult issue when using multi-residue methods capable of analyzing several hundreds of analytes. Therefore, the capability of in silico fragmentation based on a structure database ("suspect screening") instead of physical reference substances for routine targeted residue screening was investigated. The detection of fragment ions that can be predicted or explained by in silico software was utilized to reduce the number of false positives. These "proof of principle" experiments were done with a tool that is integrated into a commercial MS vendor instrument operating software (UNIFI) as well as with a platform-independent MS tool (Mass Frontier). A total of 97 analytes belonging to different chemical families were separated by reversed phase liquid chromatography and detected in a data-independent acquisition (DIA) mode using ion mobility hyphenated with quadrupole time of flight mass spectrometry. The instrument was operated in the MSE mode with alternating low and high energy traces. The fragments observed from product ion spectra were investigated using a "chopping" bond disconnection algorithm and a rule-based algorithm. The bond disconnection algorithm clearly explained more analyte product ions and a greater percentage of the spectral abundance than the rule-based software (92 out of the 97 compounds produced ≥1 explainable fragment ions). On the other hand, tests with a complex blank matrix (bovine liver extract) indicated that the chopping algorithm reports significantly more false positive fragments than the rule based software. [Figure not available: see fulltext.

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

Directory of Open Access Journals (Sweden)

Anthony Hoak

2017-03-01

Full Text Available 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.

Nova target experiments

International Nuclear Information System (INIS)

Drake, R.P.

1985-11-01

The Nova laser, at the Lawrence Livermore National Laboratory, provides unique opportunities for target experiments. It has unprecedented energy on target and significant flexibility. The paper presented by John Hunt described the capabilities and the status of Nova. This paper discusses plans for future experiments using Nova, and the present status of target experiments. We plan to perform high-quality physics experiments that exploit the unique capabilities of Nova. Because this is our goal, we are fielding an extensive array of well-characterized target diagnostics to measure the emissions from the target. The first section of this paper discusses the basic target diagnostics. We are also taking care to quantify the performance of the laser

A role for fragment-based drug design in developing novel lead compounds for central nervous system targets

Directory of Open Access Journals (Sweden)

Michael J. Wasko

2015-09-01

Full Text Available Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacologic screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening, which employs computer models of the target protein to narrow the search for possible leads. A variant of virtual screening is fragment-based drug design, an emerging in silico lead discovery method that introduces low molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for growing the lead candidate. Current efforts in virtual fragment-based drug design within central nervous system (CNS targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor binding pocket using the fragment as a scaffold. This process places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

Multi-Target Screening and Experimental Validation of Natural Products from Selaginella Plants against Alzheimer's Disease

Directory of Open Access Journals (Sweden)

Yin-Hua Deng

2017-08-01

Full Text Available Alzheimer's disease (AD is a progressive and irreversible neurodegenerative disorder which is considered to be the most common cause of dementia. It has a greater impact not only on the learning and memory disturbances but also on social and economy. Currently, there are mainly single-target drugs for AD treatment but the complexity and multiple etiologies of AD make them difficult to obtain desirable therapeutic effects. Therefore, the choice of multi-target drugs will be a potential effective strategy inAD treatment. To find multi-target active ingredients for AD treatment from Selaginella plants, we firstly explored the behaviors effects on AD mice of total extracts (TE from Selaginella doederleinii on by Morris water maze test and found that TE has a remarkable improvement on learning and memory function for AD mice. And then, multi-target SAR models associated with AD-related proteins were built based on Random Forest (RF and different descriptors to preliminarily screen potential active ingredients from Selaginella. Considering the prediction outputs and the quantity of existing compounds in our laboratory, 13 compounds were chosen to carry out the in vitro enzyme inhibitory experiments and 4 compounds with BACE1/MAO-B dual inhibitory activity were determined. Finally, the molecular docking was applied to verify the prediction results and enzyme inhibitory experiments. Based on these study and validation processes, we explored a new strategy to improve the efficiency of active ingredients screening based on trace amount of natural product and numbers of targets and found some multi-target compounds with biological activity for the development of novel drugs for AD treatment.

Origin of fragments in multifragmentation reactions

International Nuclear Information System (INIS)

Zbiri, K.; Aichelin, J.

2003-01-01

Using the quantum molecular dynamics approach we have started analyzing the results of the recent INDRA experiments at GSI facilities. For the first time we could identify a midrapidity source in which fragments are formed from an almost identical fraction of projectile and target nucleons. In smaller systems we have found this source. Nevertheless the fragment spectra at small and large angles is completely determined by the dynamics. We discuss how fragments are formed in the different regions of phase space and what they tell us about the reaction mechanism. (authors)

Investigation of Nuclear Fragmentation in Relativistic Heavy Ion Collisions Using Plastic - Nuclear - Track Detectors

CERN Multimedia

2002-01-01

In this experiment CR39 plastic nuclear track detectors will be used which are sensitive to detect relativistic nuclear fragments with charges Z@$>$5. They will be analyzed using an automatic track measuring system which was developed at the University of Siegen.\\\\ \\\\ This allows to measure large quantities of tracks in these passive detectors and to perform high statistics experiments. We intend to measure cross sections for the production of nuclear fragments from heavy ion beams at the SPS. \\\\ \\\\ The energy independence of the cross sections predicted by the idea of limiting fragmentation will be tested at high energies. In exposures with different targets we plan to analyze the factorization of the fragmentation cross sections into a target depending factor and a factor depending on the beam particle and the fragment. The cross sections for one proton remov Coulomb dissociation. \\\\ \\\\ We plan to investigate Coulomb dissociation for different targets and different energies. Fragment and projectile charges ...

Study of the multi-fragment production in asymmetric heavy ion reactions at E/A = 600 MeV

International Nuclear Information System (INIS)

Hubele, J.C.

1992-03-01

In this thesis the fragmentation of Au projectiles in collisions with light target nuclei ( 12 C, 27 Al, 64 Cu) is studied at a projectile energy of 600 MeV per nucleon. For the description of an event three observables are used: the multiplicity M lp of the light particles, the largest observed charge Z max of the projectile fragments, as well as a newly introduced obsevable Z bound , which is defined as the sum of all charge contained in complex projectile fragments (Z ≥ 2). By means of this observable different exit channels can be identified: the formation of a heavy residual nucleus by evaporation of light particles, the binary fission, the decay into IMF's (3 ≤ Z ≤ 30) and the complete decay into light particles. At the applied incident energy in the case of Au+Cu reactions each of these decay channels can be realized. The observables Z bound and M lpp are proved as suited quantities for the reconstruction of the impact parameter. Furthermore independently on the target a universal relation between Z bound and the multiplicity distribution of medium-heavy fragments is found. By simple model assumptions it is made plausible that Z bound is correlated both with the size of the projectile residue and in the mean with its excitation energy. For the characterization of the decay into IMF's the multiplicity M imf of these fragments is applied. For all three targets with increasing centrality first an increasing of the mean fragment multiplicities to maximal values of 3-4 is observed. In the case of the Cu target and suggestively also at the Al target in the most central collisions again a decreasing of the multiplicity is found. The universal Z bound behaviour is a hint to a - at least partial - equilibration of the primary projectile residue before the decay. (HSI) [de

Multi-Source Multi-Target Dictionary Learning for Prediction of Cognitive Decline.

Science.gov (United States)

Zhang, Jie; Li, Qingyang; Caselli, Richard J; Thompson, Paul M; Ye, Jieping; Wang, Yalin

2017-06-01

Alzheimer's Disease (AD) is the most common type of dementia. Identifying correct biomarkers may determine pre-symptomatic AD subjects and enable early intervention. Recently, Multi-task sparse feature learning has been successfully applied to many computer vision and biomedical informatics researches. It aims to improve the generalization performance by exploiting the shared features among different tasks. However, most of the existing algorithms are formulated as a supervised learning scheme. Its drawback is with either insufficient feature numbers or missing label information. To address these challenges, we formulate an unsupervised framework for multi-task sparse feature learning based on a novel dictionary learning algorithm. To solve the unsupervised learning problem, we propose a two-stage Multi-Source Multi-Target Dictionary Learning (MMDL) algorithm. In stage 1, we propose a multi-source dictionary learning method to utilize the common and individual sparse features in different time slots. In stage 2, supported by a rigorous theoretical analysis, we develop a multi-task learning method to solve the missing label problem. Empirical studies on an N = 3970 longitudinal brain image data set, which involves 2 sources and 5 targets, demonstrate the improved prediction accuracy and speed efficiency of MMDL in comparison with other state-of-the-art algorithms.

Quantum Correlated Multi-Fragment Reaction Imaging

Energy Technology Data Exchange (ETDEWEB)

Feagin, James M. [California State Univ., Fullerton, CA (United States)

2017-06-30

This grant supported research in basic atomic, molecular and optical physics related to the interactions of atoms with particles and fields. This report will focus on the 12 year period from 2004 to 2017, although the DOE–BES has supported my research every year since 1986. All of the support from the grant was used to pay summer salaries of the PI and students and travel to conferences and meetings. The results were in the form of publications in peer reviewed journals as well as conference invited talks and colloquiums. There were 12 peer reviewed publications in these 12+ years. Innovations in few-body science at molecular and nano levels are a critical component of on- going efforts to establish sustainable environmental and energy resources. The varied research paths taken will require the development of basic science on broad fronts with increasing flexi- bility to crossover technologies. We thus worked to extract understanding and quantum control of few-body microscopic systems based on our long-time experience with more conventional studies of correlated electrons and ions. Given the enormous advances over the past 20 years to our understanding of quantum cor- relations with photon interferometry, AMO collision science generally is ready to move beyond the one-particle, single-port momentum detection that has dominated collision physics since Rutherford. Nevertheless, our familiar theoretical tools for collision theory need to be up- graded to incorporate these more generalized measurement formalisms and ultimately to give incentive for a new generation of experiments. Our interest in these topics remains motivated by the recent surge in and success of exper- iments involving few-body atomic and molecular fragmentation and the detection of all the fragments. The research described here thus involved two parallel efforts with (i) emphasis on reaction imaging while (ii) pursuing longtime work on quantum correlated collective excitations.

Similarity of multi-fragmentation of residual nucleus created in nucleus-nucleus interactions at high energies

International Nuclear Information System (INIS)

Abdel-Hafiez, A.; Chernyavski, M.M.; Orlova, G.I.; Gulamov, K.G.; Navotny, V.SH.; Uzhinskii, V.V.

2000-01-01

Experimental data on multi-fragmentation of residual krypton nuclei created in the interactions of the krypton nuclei with photoemulsion nuclei ut energy of 0.9 GeV per nucleon are presented in a comparison with the analogous data on fragmentation of gold residual nuclei at the energy of 10.7 GeV/nucleon. It is shown for the first time that there are two regimes of nuclear multifragmentation: the former is when less than one-half of nucleons of projectile nucleus are knocked out, the later is when more than one-half of nucleons are knocked out. Residual nuclei with closed masses created at different reactions are fragmenting practically simultaneously when more than one-half of nucleons of original nuclei are knocked out. The evidence of existence of a radial flow of the spectator fragment at the decay of residual krypton nuclei is found

Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells

Czech Academy of Sciences Publication Activity Database

Ohradanova-Repic, A.; Nogueira, E.; Hartl, I.; Gomes, A.C.; Preto, A.; Steinhuber, E.; Muehlgrabner, V.; Repic, M.; Kuttke, M.; Zwirzitz, A.; Prouza, M.; Suchánek, M.; Wozniak-Knopp, G.; Hořejší, Václav; Schabbauer, G.; Cavaco-Paulo, A.; Stockinger, H.

2018-01-01

Roč. 14, č. 1 (2018), s. 123-130 ISSN 1549-9634 Institutional support: RVO:68378050 Keywords : Active targeting * Liposome functionalization * Immunoliposome * Antibody engineering * Recombinant Fab antibody fragment Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 5.720, year: 2016

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets.

Science.gov (United States)

Wasko, Michael J; Pellegrene, Kendy A; Madura, Jeffry D; Surratt, Christopher K

2015-01-01

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for "growing" the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.

Science.gov (United States)

Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang

2017-08-18

The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Conserved peptide fragmentation as a benchmarking tool for mass spectrometers and a discriminating feature for targeted proteomics.

Science.gov (United States)

Toprak, Umut H; Gillet, Ludovic C; Maiolica, Alessio; Navarro, Pedro; Leitner, Alexander; Aebersold, Ruedi

2014-08-01

Quantifying the similarity of spectra is an important task in various areas of spectroscopy, for example, to identify a compound by comparing sample spectra to those of reference standards. In mass spectrometry based discovery proteomics, spectral comparisons are used to infer the amino acid sequence of peptides. In targeted proteomics by selected reaction monitoring (SRM) or SWATH MS, predetermined sets of fragment ion signals integrated over chromatographic time are used to identify target peptides in complex samples. In both cases, confidence in peptide identification is directly related to the quality of spectral matches. In this study, we used sets of simulated spectra of well-controlled dissimilarity to benchmark different spectral comparison measures and to develop a robust scoring scheme that quantifies the similarity of fragment ion spectra. We applied the normalized spectral contrast angle score to quantify the similarity of spectra to objectively assess fragment ion variability of tandem mass spectrometric datasets, to evaluate portability of peptide fragment ion spectra for targeted mass spectrometry across different types of mass spectrometers and to discriminate target assays from decoys in targeted proteomics. Altogether, this study validates the use of the normalized spectral contrast angle as a sensitive spectral similarity measure for targeted proteomics, and more generally provides a methodology to assess the performance of spectral comparisons and to support the rational selection of the most appropriate similarity measure. The algorithms used in this study are made publicly available as an open source toolset with a graphical user interface. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach.

Science.gov (United States)

Amato, Anastasia; Lucas, Xavier; Bortoluzzi, Alessio; Wright, David; Ciulli, Alessio

2018-04-20

Plant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, we describe a successful fragment-based campaign targeting PHD fingers from the proteins BAZ2A and BAZ2B as model systems. We validated a pool of in silico fragments both biophysically and structurally and solved the first crystal structures of PHD zinc fingers in complex with fragments bound to an anchoring pocket at the histone binding site. The best-validated hits were found to displace a histone H3 tail peptide in competition assays. This work identifies new chemical scaffolds that provide suitable starting points for future ligand optimization using structure-guided approaches. The demonstrated ligandability of the PHD reader domains could pave the way for the development of chemical probes to drug this family of epigenetic readers.

Heavy fragment production cross sections from 1.05 GeV/nucleon 56Fe in C, Al, Cu, Pb, and CH2 targets

Science.gov (United States)

Zeitlin, C.; Heilbronn, L.; Miller, J.; Rademacher, S. E.; Borak, T.; Carter, T. R.; Frankel, K. A.; Schimmerling, W.; Stronach, C. E.; Chatterjee, A. (Principal Investigator)

1997-01-01

We have obtained charge-changing cross sections and partial cross sections for fragmentation of 1.05 GeV/nucleon Fe projectiles incident on H, C, Al, Cu, and Pb nuclei. The energy region covered by this experiment is critical for an understanding of galactic cosmic ray propagation and space radiation biophysics. Surviving primary beam particles and fragments with charges from 12 to 25 produced within a forward cone of half-angle 61 mrad were detected using a silicon detector telescope to identify their charge and the cross sections were calculated after correction of the measured yields for finite target thickness effects. The cross sections are compared to model calculations and to previous measurements. Cross sections for the production of fragments with even-numbered nuclear charges are seen to be enhanced in almost all cases.

Universality of spectator fragmentation at relativistic bombarding energies

International Nuclear Information System (INIS)

Schuettauf, A.; Woerner, A.

1996-06-01

Multi-fragment decays of 129 Xe, 197 Au, and 238 U projectiles in collisions with Be, C, Al, Cu, In, Au, and U targets at energies between E/A=400 MeV and 1000 MeV have been studied with the ALADIN forward-spectrometer at SIS. By adding an array of 84 Si-CsI(Tl) telescopes the solid-angle coverage of the setup was extended to θ lab =16 . This permitted the complete detection of fragments from the projectile-spectator source. The dominant feature of the systematic set of data is the Z bound universality that is obeyed by the fragment multiplicities and correlations. These observables are invariant with respect to the entrance channel if plotted as a function of Z bound , where Z bound is the sum of the atomic numbers Z i of all projectile fragments with Z i ≥2. No significant dependence on the bombarding energy nor on the target mass is observed. The dependence of the fragment multiplicity on the projectile mass follows a linear scaling law. The reasons for and the limits of the observed universality of spectator fragmentation are explored within the realm of the available data and with model studies. It is found that the universal properties should persist up to much higher bombarding energies than explored in this work and that they are consistent with universal features exhibited by the intranuclear cascade and statistical multifragmentation models. (orig.)

Evaluation of radioiodinated and radiocopper labeled monovalent fragments of monoclonal antibody chCE7 for targeting of neuroblastoma

International Nuclear Information System (INIS)

Carrel, Francois; Amstutz, Hanspeter; Novak-Hofer, Ilse; Schubiger, P. August

1997-01-01

Monovalent fragments of antineuroblastoma antibody mAb chCE7 were evaluated for their in vitro and in vivo tumor cell binding properties. Single chain fragments were constructed from the variable region genes cloned from hybridoma cells, expressed in E.coli and purified by metal chelate affinity chromatography. Radioiodinated CE7-scFv fragments were found to bind with high affinity (K d ∼10 -9 M) to target cells in vitro but formed aggregates at 37 deg. C, and bound to serum proteins in vitro and in vivo. Circular Dichroism spectra revealed the protein to be in a conformationally altered form and no permanent 'refolding' could be achieved. In contrast, chCE7-Fab fragments were found to bind to target tumor cells with similar affinity than the parent mAb chCE7 (K d ∼10 -10 M), showed no tendency to aggregate and were stable in serum both in vitro and in vivo. Kinetics of association and dissociation of radioiodinated scFv and Fab fragments were found to be rapid. Radioiodination with the Iodogen method led to impaired immunoreactivity which was found to further increase the off- rates of radioiodinated fragments from tumor cells. Radioiodination with the Bolton-Hunter reagent as well as labeling of chCE7-Fab fragments with 67 Cu via the macrocyclic CPTA ligand led to fully immunoreactive Fab fragments. Radioiodinated and radiocopper labeled monovalent CE7 fragments did not internalize into target tumor cells as the parent mAb and its F(ab') 2 fragment. A comparison of the biodistribution in tumor bearing nude mice of the radiocopper labeled monovalent, non internalizing Fab fragments with the internalizing divalent F(ab') 2 fragments showed in both cases high levels of radioactivity in the kidneys. Concerning tumor uptake, radioactivity from both internalizing and non internalizing fragments remained associated with tumor tissue for longer times than in case of the corresponding radioiodinated fragments. When compared with the radioiodinated forms, tumor uptake

Fragmentation of Pb-Projectiles at SPS Energies

CERN Multimedia

2002-01-01

% EMU17 \\\\ \\\\ We have exposed stacks consisting of solid state nuclear track detectors (CR-39 plastic and BP-1 glass) and different target materials at the SPS to beams of Pb projectiles. Our detectors record tracks of relativistic nuclei with charge numbers of Z~$\\geq$~6 for CR-39 and Z~$\\geq$75 for BP-1. After development of the tracks by etching they are detected and measured using completely automated microscope systems. Thus experiments with high statistics are possible. \\\\ \\\\BP-1 detectors were exposed to measure total charge changing cross sections and elemental production cross sections for heavy projectile fragments. These experiments were performed for different targets CH$ _{2} $, C, Al, Cu, Ag and Pb. Comparison of the results for different targets allows to investigate contributions to charge changing reactions by electromagnetic dissociation. Multifragmentation events in which several intermediate mass fragments are emitted from the heavy Pb projectile are studied using stacks containing CR-39 d...

Inclusive projectile fragmentation in the spectator model

International Nuclear Information System (INIS)

Hussein, M.S.; McVoy, K.W.

1985-01-01

Crazing-angle single spectra for projectile fragments from nuclear collisions exhibit a broad peak centered near the beam velocity, suggesting that these observed fragments play only a 'spectator' role in the reaction. Using only this spectator assumption (but not DWBA), it is found that a 'prior form' formulation of the reaction leads, via closure, to a -type estimate of the inclusive spectator spectrum, thus relating it to the reaction cross section for the 'participant' with the target. It is shown explicitly that this expression includes an improved multi-channel version of the Udagawa-Tamura formula for the 'breakup-fusion' or incomplete fusion cross section, and identifies it as the fluctuation part of the participant-target reaction cross section. A Glauber-type estimate of the distorted wave functions which enter clearly shows how the width of the peak in the spectator spectrum arises from the 'Fermi motion' within the projectile, as in the simple Serber model, but is modified by the 'overlap geometry' of the collision. (Author) [pt

Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.

Science.gov (United States)

Kobayashi, Masakazu; Retra, Kim; Figaroa, Francis; Hollander, Johan G; Ab, Eiso; Heetebrij, Robert J; Irth, Hubertus; Siegal, Gregg

2010-09-01

Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the first stage of the process be optimized. Here the authors compare the 3 most commonly used methods for hit discovery in FBDD: high concentration screening (HCS), solution ligand-observed nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR). They selected the commonly used saturation transfer difference (STD) NMR spectroscopy and the proprietary target immobilized NMR screening (TINS) as representative of the array of possible NMR methods. Using a target typical of FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak interactions. They also find a good correlation between TINS and STD for tighter binding ligands, but the ability of STD to detect ligands with affinity weaker than 1 mM K(D) is limited. Similarly, they find that SPR detection is most suited to ligands that bind with K(D) better than 1 mM. However, the good correlation between SPR and potency in a bioassay makes this a good method for hit validation and characterization studies.

Azimuthal Anisotropies in Nuclear Fragmentation

International Nuclear Information System (INIS)

Dabrowska, A.; Szarska, M.; Trzupek, A.; Wolter, W.; Wosiek, B.

2002-01-01

The directed and elliptic flow of fragments emitted from the excited projectile nuclei has been observed for 158 AGeV Pb collisions with the lead and plastic targets. For comparison the flow analysis has been performed for 10.6 AGeV Au collisions with the emulsion target. The strong directed flow of heaviest fragments is found. Light fragments exhibit directed flow opposite to that of heavy fragments. The elliptic flow for all multiply charged fragments is positive and increases with the charge of the fragment. The observed flow patterns in the fragmentation of the projectile nucleus are practically independent of the mass of the target nucleus and the collision energy. Emission of fragments in nuclear multifragmentation shows similar, although weaker, flow effects. (author)

Collision induced fragmentation dynamics of small metallic clusters; Dynamique de fragmentation induite par collision de petits agregats metalliques

Energy Technology Data Exchange (ETDEWEB)

Picard, Y

1999-04-15

The goal of this work is the complete analysis of the fragmentation of alkali clusters (Na{sub n}{sup +} (n < 10), NaK{sup +} and K{sub 2}{sup +}) induced by collision with light atomic (He) or molecular (H{sub 2}) targets. The main point is to study how the energy is transmitted to the cluster during the collision and how this energy is shared among the various degrees of freedom of the system and leads to its fragmentation. Two types of interactions govern the collision induced dissociation processes: on one hand, the electronic mechanisms where the target perturbs the electronic cloud and brings the molecule into a dissociative state, and on the other hand, the impulsive mechanisms where the momentum transferred to the atomic cores leads to the rotational-vibrational dissociation of the molecule. The experimental procedure is based on the measurement of the velocity vectors of the outgoing fragments detected in coincidence. This allows to reconstruct the full kinematics of the fragmentation and to separate and characterize for the first time the two types of interactions. The two basic mechanisms of collision induced dissociation are then clearly resolved for the diatomic molecule Na{sub 2}{sup +}. For the heteronuclear molecular ion NaK{sup +}, it is shown that the dissociation process is due to a combination of electronic and impulsive mechanisms in some of the dissociation pathways. The extension to the study of metallic clusters Na{sub n}{sup +} (n < 10) fragmentation shows the role and the relative importance of the electronic and impulsive mechanisms and their evolution with the cluster size. The complete analysis of Na{sub 3}{sup +} multi-fragmentation is also presented. (author)

Experiment of ambient temperature distribution in ICF driver's target building

International Nuclear Information System (INIS)

Zhou Yi; He Jie; Yang Shujuan; Zhang Junwei; Zhou Hai; Feng Bin; Xie Na; Lin Donghui

2009-01-01

An experiment is designed to explore the ambient temperature distribution in an ICF driver's target building, Multi-channel PC-2WS temperature monitoring recorders and PTWD-2A precision temperature sensors are used to measure temperatures on the three vertical cross-sections in the building, and the collected data have been handled by MATLAB. The experiment and analysis show that the design of the heating ventilation and air conditioning (HVAC) system can maintain the temperature stability throughout the building. However, because of the impact of heat in the target chamber, larger local environmental temperature gradients appear near the marshalling yard, the staff region on the middle floor, and equipments on the lower floor which needs to be controlled. (authors)

A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins.

Science.gov (United States)

Joshi, Priyanka; Chia, Sean; Habchi, Johnny; Knowles, Tuomas P J; Dobson, Christopher M; Vendruscolo, Michele

2016-03-14

The aggregation process of intrinsically disordered proteins (IDPs) has been associated with a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Currently, however, no drug in clinical use targets IDP aggregation. To facilitate drug discovery programs in this important and challenging area, we describe a fragment-based approach of generating small-molecule libraries that target specific IDPs. The method is based on the use of molecular fragments extracted from compounds reported in the literature to inhibit of the aggregation of IDPs. These fragments are used to screen existing large generic libraries of small molecules to form smaller libraries specific for given IDPs. We illustrate this approach by describing three distinct small-molecule libraries to target, Aβ, tau, and α-synuclein, which are three IDPs implicated in Alzheimer's and Parkinson's diseases. The strategy described here offers novel opportunities for the identification of effective molecular scaffolds for drug discovery for neurodegenerative disorders and to provide insights into the mechanism of small-molecule binding to IDPs.

Validation of ASTEC v2.0 corium jet fragmentation model using FARO experiments

International Nuclear Information System (INIS)

Hermsmeyer, S.; Pla, P.; Sangiorgi, M.

2015-01-01

Highlights: • Model validation base extended to six FARO experiments. • Focus on the calculation of the fragmented particle diameter. • Capability and limits of the ASTEC fragmentation model. • Sensitivity analysis of model outputs. - Abstract: ASTEC is an integral code for the prediction of Severe Accidents in Nuclear Power Plants. As such, it needs to cover all physical processes that could occur during accident progression, yet keeping its models simple enough for the ensemble to stay manageable and produce results within an acceptable time. The present paper is concerned with the validation of the Corium jet fragmentation model of ASTEC v2.0 rev3 by means of a selection of six experiments carried out within the FARO facility. The different conditions applied within these six experiments help to analyse the model behaviour in different situations and to expose model limits. In addition to comparing model outputs with experimental measurements, sensitivity analyses are applied to investigate the model. Results of the paper are (i) validation runs, accompanied by an identification of situations where the implemented fragmentation model does not match the experiments well, and discussion of results; (ii) its special attention to the models calculating the diameter of fragmented particles, the identification of a fault in one model implemented, and the discussion of simplification and ad hoc modification to improve the model fit; and, (iii) an investigation of the sensitivity of predictions towards inputs and parameters. In this way, the paper offers a thorough investigation of the merit and limitation of the fragmentation model used in ASTEC

Projectile and target fragmentation at intermediate energies (20 MeV <= E/A <= 100 MeV)

International Nuclear Information System (INIS)

Dayras, R.A.

1985-04-01

In order to follow the evolution of the reaction mechanisms in the transition region of the intermediate energy range, detailed studies of projectile-like fragments from a 44 MeV/u 40 Ar projectile bombarding 27 Al and sup(NAT)T: targets have been made. Experimental results are given. Discussion of the data is presented: transfer reactions, isotopic distributions, the fragmentation model, and abrasion model are used in the discussion

Tyrosine kinase inhibitors: Multi-targeted or single-targeted?

Science.gov (United States)

Broekman, Fleur; Giovannetti, Elisa; Peters, Godefridus J

2011-02-10

Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients.

Non-statistical fluctuations in fragmentation of target nuclei in high energy nuclear interactions

International Nuclear Information System (INIS)

Ghosh, Dipak; Ghosh, Premomoy; Ghosh, Alokananda; Roy, Jaya

1994-01-01

Analysis of target fragmented ''black'' particles in nuclear emulsion from high energy relativistic interactions initiated by 16 O at 2.1 GeV/nucleon and 12 C and 24 Mg at 4.5 GeV/nucleon reveal the existence of non-statistical fluctuations in the azimuthal plane of interaction. The asymmetry or the non-statistical fluctuations, while found to be independent of projectile mass or incident energy, are dependent on the excitation energy of the target nucleus. (Author)

In silico design of targeted SRM-based experiments

Directory of Open Access Journals (Sweden)

Nahnsen Sven

2012-11-01

Full Text Available Abstract Selected reaction monitoring (SRM-based proteomics approaches enable highly sensitive and reproducible assays for profiling of thousands of peptides in one experiment. The development of such assays involves the determination of retention time, detectability and fragmentation properties of peptides, followed by an optimal selection of transitions. If those properties have to be identified experimentally, the assay development becomes a time-consuming task. We introduce a computational framework for the optimal selection of transitions for a given set of proteins based on their sequence information alone or in conjunction with already existing transition databases. The presented method enables the rapid and fully automated initial development of assays for targeted proteomics. We introduce the relevant methods, report and discuss a step-wise and generic protocol and we also show that we can reach an ad hoc coverage of 80 % of the targeted proteins. The presented algorithmic procedure is implemented in the open-source software package OpenMS/TOPP.

Measures to overcome consequences of agricultural land fragmentation: European experience and Ukrainian realities

Directory of Open Access Journals (Sweden)

Andriy Popov

2016-03-01

Full Text Available One of the land reform implementation results in Ukraine is the distribution of the state-owned agricultural land to the rural population in the form of physical land parcels. As a consequence, however, the land was subdivided into many small units. This land fragmentation has led to fundamental changes in the formation of the new agricultural enterprises and brought some negative consequences in their functioning. The problem of the land fragmentation in Ukraine is quite new and uninvestigated. The aim of the article is to analyze the existing measures (instruments in European countries for reducing the effects of agricultural land fragmentation and to determine the possibility of «transplantability» of Western experience to Ukraine. The principal measures to decrease the agricultural land fragmentation in European countries are: voluntary parcel exchange, land banking and land consolidation. The article presents the characteristics and comparative analysis of these measures. One of the four types of land fragmentation is a main problem of Ukraine, namely the discrepancy between the landownership and the land use. The Western European countries have been used the three instruments for reducing only two types of land fragmentation: the land use fragmentation and the internal fragmentation. Consequently, the using of Western European measures to decrease agricultural land fragmentation is impossible without their adaptation to the Ukrainian realities. Therefore, the actual problem in Ukraine today is to find the own measures to overcome the problem of agricultural land fragmentation based on the Western European experience.

Hunting for CDF multi-muon ''ghost'' events at collider and fixed-target experiments

International Nuclear Information System (INIS)

Bornhauser, Nicki; Drees, Manuel

2011-01-01

In 2008 the CDF collaboration discovered a large excess of events containing two or more muons, at least one of which seemed to have been produced outside the beam pipe. We investigate whether similar ''ghost'' events could (and should) have been seen in already completed experiments. The CDF di-muon data can be reproduced by a simple model where a relatively light X particle undergoes 4-body decay. This model predicts a large number of ghost events in Fermilab fixed-target experiments E772, E789 and E866, applying the cuts optimized for analyses of Drell-Yan events. A correct description of events with more than two muons requires a more complicated model, where two X particles are produced from a very broad resonance Y. This model can be tested in fixed-target experiments only if the cut on the angles, or rapidities, of the muons can be relaxed. Either way, the UA1 experiment at the CERN p anti p collider should have observed O(100) ghost events. (orig.)

Large scale meta-analysis of fragment-based screening campaigns: privileged fragments and complementary technologies.

Science.gov (United States)

Kutchukian, Peter S; Wassermann, Anne Mai; Lindvall, Mika K; Wright, S Kirk; Ottl, Johannes; Jacob, Jaison; Scheufler, Clemens; Marzinzik, Andreas; Brooijmans, Natasja; Glick, Meir

2015-06-01

A first step in fragment-based drug discovery (FBDD) often entails a fragment-based screen (FBS) to identify fragment "hits." However, the integration of conflicting results from orthogonal screens remains a challenge. Here we present a meta-analysis of 35 fragment-based campaigns at Novartis, which employed a generic 1400-fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we sought to investigate three questions: (1) What makes a fragment amenable for FBS? (2) How do hits from different fragment screening technologies and target classes compare with each other? (3) What is the best way to pair FBS assay technologies? In doing so, we identified substructures that were privileged for specific target classes, as well as fragments that were privileged for authentic activity against many targets. We also revealed some of the discrepancies between technologies. Finally, we uncovered a simple rule of thumb in screening strategy: when choosing two technologies for a campaign, pairing a biochemical and biophysical screen tends to yield the greatest coverage of authentic hits. © 2014 Society for Laboratory Automation and Screening.

Multi-target-qubit unconventional geometric phase gate in a multi-cavity system.

Science.gov (United States)

Liu, Tong; Cao, Xiao-Zhi; Su, Qi-Ping; Xiong, Shao-Jie; Yang, Chui-Ping

2016-02-22

Cavity-based large scale quantum information processing (QIP) may involve multiple cavities and require performing various quantum logic operations on qubits distributed in different cavities. Geometric-phase-based quantum computing has drawn much attention recently, which offers advantages against inaccuracies and local fluctuations. In addition, multiqubit gates are particularly appealing and play important roles in QIP. We here present a simple and efficient scheme for realizing a multi-target-qubit unconventional geometric phase gate in a multi-cavity system. This multiqubit phase gate has a common control qubit but different target qubits distributed in different cavities, which can be achieved using a single-step operation. The gate operation time is independent of the number of qubits and only two levels for each qubit are needed. This multiqubit gate is generic, e.g., by performing single-qubit operations, it can be converted into two types of significant multi-target-qubit phase gates useful in QIP. The proposal is quite general, which can be used to accomplish the same task for a general type of qubits such as atoms, NV centers, quantum dots, and superconducting qubits.

Fragmentation of the C60 molecule in collision with light ions studied by a multi-correlation technique. Cross-sections, electron spectroscopy

International Nuclear Information System (INIS)

Rentenier, A.

2004-04-01

A quantitative study of the C60 fullerenes fragmentation in collision with light ions (H n + with n=1,2,3, He q+ with q=1,2) in the velocity range 0,1 - 2,3 u.a.) is presented. The multi-correlation technique, developed between fragment ions and electrons with well defined energy, has enlightened some of the dependences and properties of fragmentation mechanisms (cross sections, electron spectroscopy, size distributions, kinetic energy of fragment ions, Campi's scatter plot, activation energies). The deposited energy hence appeared as an important parameter. Cross sections have been measured, for the first time, for all the collisional processes. Ionisation and capture only depends on the collision velocity. On the other hand, scaling laws with the deposited energy have been observed for the cross sections of multifragmentation, which depends on the collision energy and the nature of the projectile. The deposited energy has also been found as an essential parameter to understand the evolution of the charged fragment size distributions. The electron spectroscopy, achieved at an emission angle of 35 degrees, showed spectra peaked at important energies (from 5 to 20 eV). The spectra shape depends on the collision velocity. A first theoretical analysis points out the link between the observed energy distribution and the presence of a centrifugal potential barrier. Finally, correlation experiments between produced ions and electron energy reveal that electron energy increases with internal energy. (author)

Multi-targeted priming for genome-wide gene expression assays

Directory of Open Access Journals (Sweden)

Adomas Aleksandra B

2010-08-01

Full Text Available Abstract Background Complementary approaches to assaying global gene expression are needed to assess gene expression in regions that are poorly assayed by current methodologies. A key component of nearly all gene expression assays is the reverse transcription of transcribed sequences that has traditionally been performed by priming the poly-A tails on many of the transcribed genes in eukaryotes with oligo-dT, or by priming RNA indiscriminately with random hexamers. We designed an algorithm to find common sequence motifs that were present within most protein-coding genes of Saccharomyces cerevisiae and of Neurospora crassa, but that were not present within their ribosomal RNA or transfer RNA genes. We then experimentally tested whether degenerately priming these motifs with multi-targeted primers improved the accuracy and completeness of transcriptomic assays. Results We discovered two multi-targeted primers that would prime a preponderance of genes in the genomes of Saccharomyces cerevisiae and Neurospora crassa while avoiding priming ribosomal RNA or transfer RNA. Examining the response of Saccharomyces cerevisiae to nitrogen deficiency and profiling Neurospora crassa early sexual development, we demonstrated that using multi-targeted primers in reverse transcription led to superior performance of microarray profiling and next-generation RNA tag sequencing. Priming with multi-targeted primers in addition to oligo-dT resulted in higher sensitivity, a larger number of well-measured genes and greater power to detect differences in gene expression. Conclusions Our results provide the most complete and detailed expression profiles of the yeast nitrogen starvation response and N. crassa early sexual development to date. Furthermore, our multi-targeting priming methodology for genome-wide gene expression assays provides selective targeting of multiple sequences and counter-selection against undesirable sequences, facilitating a more complete and

Knowledge-based Fragment Binding Prediction

Science.gov (United States)

Tang, Grace W.; Altman, Russ B.

2014-01-01

Target-based drug discovery must assess many drug-like compounds for potential activity. Focusing on low-molecular-weight compounds (fragments) can dramatically reduce the chemical search space. However, approaches for determining protein-fragment interactions have limitations. Experimental assays are time-consuming, expensive, and not always applicable. At the same time, computational approaches using physics-based methods have limited accuracy. With increasing high-resolution structural data for protein-ligand complexes, there is now an opportunity for data-driven approaches to fragment binding prediction. We present FragFEATURE, a machine learning approach to predict small molecule fragments preferred by a target protein structure. We first create a knowledge base of protein structural environments annotated with the small molecule substructures they bind. These substructures have low-molecular weight and serve as a proxy for fragments. FragFEATURE then compares the structural environments within a target protein to those in the knowledge base to retrieve statistically preferred fragments. It merges information across diverse ligands with shared substructures to generate predictions. Our results demonstrate FragFEATURE's ability to rediscover fragments corresponding to the ligand bound with 74% precision and 82% recall on average. For many protein targets, it identifies high scoring fragments that are substructures of known inhibitors. FragFEATURE thus predicts fragments that can serve as inputs to fragment-based drug design or serve as refinement criteria for creating target-specific compound libraries for experimental or computational screening. PMID:24762971

A collagen-binding EGFR antibody fragment targeting tumors with a collagen-rich extracellular matrix.

Science.gov (United States)

Liang, Hui; Li, Xiaoran; Wang, Bin; Chen, Bing; Zhao, Yannan; Sun, Jie; Zhuang, Yan; Shi, Jiajia; Shen, He; Zhang, Zhijun; Dai, Jianwu

2016-02-17

Many tumors over-express collagen, which constitutes the physical scaffold of tumor microenvironment. Collagen has been considered to be a target for cancer therapy. The collagen-binding domain (CBD) is a short peptide, which could bind to collagen and achieve the sustained release of CBD-fused proteins in collagen scaffold. Here, a collagen-binding EGFR antibody fragment was designed and expressed for targeting the collagen-rich extracellular matrix in tumors. The antibody fragment (Fab) of cetuximab was fused with CBD (CBD-Fab) and expressed in Pichia pastoris. CBD-Fab maintained antigen binding and anti-tumor activity of cetuximab and obtained a collagen-binding ability in vitro. The results also showed CBD-Fab was mainly enriched in tumors and had longer retention time in tumors in A431 s.c. xenografts. Furthermore, CBD-Fab showed a similar therapeutic efficacy as cetuximab in A431 xenografts. Although CBD-Fab hasn't showed better therapeutic effects than cetuximab, its smaller molecular and special target may be applicable as antibody-drug conjugates (ADC) or immunotoxins.

Fusion-based multi-target tracking and localization for intelligent surveillance systems

Science.gov (United States)

Rababaah, Haroun; Shirkhodaie, Amir

2008-04-01

In this paper, we have presented two approaches addressing visual target tracking and localization in complex urban environment. The two techniques presented in this paper are: fusion-based multi-target visual tracking, and multi-target localization via camera calibration. For multi-target tracking, the data fusion concepts of hypothesis generation/evaluation/selection, target-to-target registration, and association are employed. An association matrix is implemented using RGB histograms for associated tracking of multi-targets of interests. Motion segmentation of targets of interest (TOI) from the background was achieved by a Gaussian Mixture Model. Foreground segmentation, on other hand, was achieved by the Connected Components Analysis (CCA) technique. The tracking of individual targets was estimated by fusing two sources of information, the centroid with the spatial gating, and the RGB histogram association matrix. The localization problem is addressed through an effective camera calibration technique using edge modeling for grid mapping (EMGM). A two-stage image pixel to world coordinates mapping technique is introduced that performs coarse and fine location estimation of moving TOIs. In coarse estimation, an approximate neighborhood of the target position is estimated based on nearest 4-neighbor method, and in fine estimation, we use Euclidean interpolation to localize the position within the estimated four neighbors. Both techniques were tested and shown reliable results for tracking and localization of Targets of interests in complex urban environment.

Non-statistical fluctuations in fragmentation of target nuclei in high energy nuclear interactions

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Dipak; Ghosh, Premomoy; Ghosh, Alokananda; Roy, Jaya [Jadavpur Univ., Calcutta (India)

1994-07-01

Analysis of target fragmented ''black'' particles in nuclear emulsion from high energy relativistic interactions initiated by [sup 16]O at 2.1 GeV/nucleon and [sup 12]C and [sup 24]Mg at 4.5 GeV/nucleon reveal the existence of non-statistical fluctuations in the azimuthal plane of interaction. The asymmetry or the non-statistical fluctuations, while found to be independent of projectile mass or incident energy, are dependent on the excitation energy of the target nucleus. (Author).

Removal of oxidative fragments from chemically functionalized multi-walled carbon nanotubes (MWCNTs)

International Nuclear Information System (INIS)

Mohd Hamzah Harun; Whitby, Raymond; Khairul Zaman Dahlan; Nik Ghazali Nik Salleh; Mohd Sofian Alias; Mahathir Mohamed; Mohd Yusof Hamzah; Mohd Faizal Abdul Rahman

2010-01-01

Acid oxidized multi-walled carbon nano tubes (MWCNTs) were prepared by refluxing MWCNTs with nitric acid (70 %). To remove the oxidative fragment/ debris, in which partially attached onto the carbon nano tubes lattice, the functionalized MWCNTs (f-MWCNTs) then were refluxed with NaOH (1M) and followed with HCl (1M) wash. The presence of carboxylic group that covalently attached onto the MWCNTs lattice are confirmed with acid-base titration. The TEM image shows the comparison of pure MWCNTs, f-MWCNTs and base-acid wash of f-MWCNTs. (author)

Target fragmentation in proton-nucleus and16O-nucleus reactions at 60 and 200 GeV/nucleon

Science.gov (United States)

Albrecht, R.; Awes, T. C.; Baktash, C.; Beckmann, P.; Claesson, G.; Berger, F.; Bock, R.; Dragon, L.; Ferguson, R. L.; Franz, A.; Garpman, S.; Glasow, R.; Gustafsson, H. Å.; Gutbrod, H. H.; Kampert, K. H.; Kolb, B. W.; Kristiansson, P.; Lee, I. Y.; Löhner, H.; Lund, I.; Obenshain, F. E.; Oskarsson, A.; Otterlund, I.; Peitzmann, T.; Persson, S.; Plasil, F.; Poskanzer, A. M.; Purschke, M.; Ritter, H. G.; Santo, R.; Schmidt, H. R.; Siemiarczuk, T.; Sorensen, S. P.; Stenlund, E.; Young, G. R.

1988-03-01

Target remnants with ZPlastic Ball detector. The excitation energy of the target spectator matter in central oxygen-induced collisions is found to be high enough to allow for complete disintegration of the target nucleus into fragments with Z<3. The average longitudinal momentum transfer per proton to the target in central collisions is considerably higher in the case of16O-induced reactions (≈300 MeV/c) than in proton-induced reactions (≈130 MeV/c). The baryon rapidity distributions are roughly in agreement with one-fluid hydrodynamical calculations at 60 GeV/nucleon16O+Au but are in disagreement at 200 GeV/nucleon, indicating the higher degree of transparency at the higher bombarding energy. Both, the transverse momenta of target spectators and the entropy produced in the target fragmentation region are compared to those attained in head-on collisions of two heavy nuclei at Bevalac energies. They are found to be comparable or do even exceed the values for the participant matter at beam energies of about 1 2 GeV/nucleon.

Multi-Agent Cooperative Target Search

Directory of Open Access Journals (Sweden)

Jinwen Hu

2014-05-01

Full Text Available This paper addresses a vision-based cooperative search for multiple mobile ground targets by a group of unmanned aerial vehicles (UAVs with limited sensing and communication capabilities. The airborne camera on each UAV has a limited field of view and its target discriminability varies as a function of altitude. First, by dividing the whole surveillance region into cells, a probability map can be formed for each UAV indicating the probability of target existence within each cell. Then, we propose a distributed probability map updating model which includes the fusion of measurement information, information sharing among neighboring agents, information decay and transmission due to environmental changes such as the target movement. Furthermore, we formulate the target search problem as a multi-agent cooperative coverage control problem by optimizing the collective coverage area and the detection performance. The proposed map updating model and the cooperative control scheme are distributed, i.e., assuming that each agent only communicates with its neighbors within its communication range. Finally, the effectiveness of the proposed algorithms is illustrated by simulation.

Analytical and numerical description of the PELE fragmentation upon impact with thin target plates

NARCIS (Netherlands)

Verreault, J.

2015-01-01

The PELE ammunition is characterized by a low-density filling material surrounded by a high-density brittle jacket material. An analytical model describing the fragmentation of this ammunition behind a target plate is presented. This model assumes uniaxial strain in the filling and uses the

Target fragmentation in deep inelastic scattering of 14.5 GeV electrons from nuclei

International Nuclear Information System (INIS)

Degtyarenko, P.; Gavrilov, V.; Shuvalov, S.

1993-01-01

Results will be presented for inclusive pion, kaon, proton and deuteron electroproduction from light nuclei (mainly 12 C and 16 O) of the residual gas in the beam pipe of the TPC/2γ detector at SLAC. Counter-circulating beams of 14.5 GeV electrons and positrons were used. Comparison will be made with the fragmentation of 2 H, 40 Ar, and Xe target nuclei in several regions of Q 2 and ν. The dependence of the hadron production on the hadron's kinetic energy, emission angle, and x f will be presented. The results will be compared with models of nuclear fragmentation

A large-scale forest fragmentation experiment: the Stability of Altered Forest Ecosystems Project

Science.gov (United States)

Ewers, Robert M.; Didham, Raphael K.; Fahrig, Lenore; Ferraz, Gonçalo; Hector, Andy; Holt, Robert D.; Kapos, Valerie; Reynolds, Glen; Sinun, Waidi; Snaddon, Jake L.; Turner, Edgar C.

2011-01-01

Opportunities to conduct large-scale field experiments are rare, but provide a unique opportunity to reveal the complex processes that operate within natural ecosystems. Here, we review the design of existing, large-scale forest fragmentation experiments. Based on this review, we develop a design for the Stability of Altered Forest Ecosystems (SAFE) Project, a new forest fragmentation experiment to be located in the lowland tropical forests of Borneo (Sabah, Malaysia). The SAFE Project represents an advance on existing experiments in that it: (i) allows discrimination of the effects of landscape-level forest cover from patch-level processes; (ii) is designed to facilitate the unification of a wide range of data types on ecological patterns and processes that operate over a wide range of spatial scales; (iii) has greater replication than existing experiments; (iv) incorporates an experimental manipulation of riparian corridors; and (v) embeds the experimentally fragmented landscape within a wider gradient of land-use intensity than do existing projects. The SAFE Project represents an opportunity for ecologists across disciplines to participate in a large initiative designed to generate a broad understanding of the ecological impacts of tropical forest modification. PMID:22006969

A large-scale forest fragmentation experiment: the Stability of Altered Forest Ecosystems Project.

Science.gov (United States)

Ewers, Robert M; Didham, Raphael K; Fahrig, Lenore; Ferraz, Gonçalo; Hector, Andy; Holt, Robert D; Kapos, Valerie; Reynolds, Glen; Sinun, Waidi; Snaddon, Jake L; Turner, Edgar C

2011-11-27

Opportunities to conduct large-scale field experiments are rare, but provide a unique opportunity to reveal the complex processes that operate within natural ecosystems. Here, we review the design of existing, large-scale forest fragmentation experiments. Based on this review, we develop a design for the Stability of Altered Forest Ecosystems (SAFE) Project, a new forest fragmentation experiment to be located in the lowland tropical forests of Borneo (Sabah, Malaysia). The SAFE Project represents an advance on existing experiments in that it: (i) allows discrimination of the effects of landscape-level forest cover from patch-level processes; (ii) is designed to facilitate the unification of a wide range of data types on ecological patterns and processes that operate over a wide range of spatial scales; (iii) has greater replication than existing experiments; (iv) incorporates an experimental manipulation of riparian corridors; and (v) embeds the experimentally fragmented landscape within a wider gradient of land-use intensity than do existing projects. The SAFE Project represents an opportunity for ecologists across disciplines to participate in a large initiative designed to generate a broad understanding of the ecological impacts of tropical forest modification.

Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

Directory of Open Access Journals (Sweden)

Katerina T. Xenaki

2017-10-01

Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

Extending multi-tenant architectures: a database model for a multi-target support in SaaS applications

Science.gov (United States)

Rico, Antonio; Noguera, Manuel; Garrido, José Luis; Benghazi, Kawtar; Barjis, Joseph

2016-05-01

Multi-tenant architectures (MTAs) are considered a cornerstone in the success of Software as a Service as a new application distribution formula. Multi-tenancy allows multiple customers (i.e. tenants) to be consolidated into the same operational system. This way, tenants run and share the same application instance as well as costs, which are significantly reduced. Functional needs vary from one tenant to another; either companies from different sectors run different types of applications or, although deploying the same functionality, they do differ in the extent of their complexity. In any case, MTA leaves one major concern regarding the companies' data, their privacy and security, which requires special attention to the data layer. In this article, we propose an extended data model that enhances traditional MTAs in respect of this concern. This extension - called multi-target - allows MT applications to host, manage and serve multiple functionalities within the same multi-tenant (MT) environment. The practical deployment of this approach will allow SaaS vendors to target multiple markets or address different levels of functional complexity and yet commercialise just one single MT application. The applicability of the approach is demonstrated via a case study of a real multi-tenancy multi-target (MT2) implementation, called Globalgest.

"1"2C fragmentation on thin targets at 95 MeV/A study for hadrontherapy

International Nuclear Information System (INIS)

Dudouet, Jeremie

2014-01-01

The nuclear models need to be improved in order to reach the required accuracy for a reference simulation code for hadrontherapy. In this context, two experiments have been performed by our collaboration on May 2011 and September 2013 at GANIL to study nuclear reactions of 95 MeV/u "1"2C ions on thin targets of medical interest to measure the double differential fragmentation cross sections of each produced isotope. These experimental data have been compared with Monte-Carlo simulations. Different nuclear models provided by the GEANT4 simulation toolkit have firstly been tested. These simulations revealed discrepancies up to one order of magnitude. The phenomenological model HIPSE has then been used and has shown that the overlapping region of two colliding nuclei needs to be taken into account in order to reproduce the kinematics of the emitted fragments at intermediates energies. Due to the difficulties encountered by these models in the data reproduction, a new model is currently under development: SLIIPIE. This one is a semi-microscopic model, built from a participant-spectator geometrical approach. This model was also compared to the experimental data for "1"2C+"1"2C reactions at 95 MeV/A giving promising results. (author) [fr

Contribution to the design, fulfillment, and data analysis of fission fragment yields of the SOFIA experiment at GSI

International Nuclear Information System (INIS)

Pellereau, Eric

2013-01-01

The isotopic fission yields of U 238 following the SOFIA experiment, conducted at the GSI facility (Darmstadt), are presented here. This experiment takes advantage of the inverse kinematics technique at relativistic energies. Benefits are several: fission fragments are highly focused (high geometrical efficiency) and are also completely stripped, which greatly simplifies their nuclear charge measurement. The first detector of the SOFIA setup is an active target in which fission occurs via electromagnetic excitation, followed by an ionization chamber to measure the nuclear charge and the horizontal angle of both fission fragments. The masses are deduced by the bending radius measurement of the fragments, deflected by a strong magnet (ALADIN), thanks to two position detectors (MWPC), and also by a highly resolved time-of-flight measurement (40 ps FWHM) so that heavy neighboring isotopes can be separated. The data analysis shows that the main goals are achieved since the isotopic separation is reached over the whole range of the fission fragments. A strong even-odd effect is seen in the charge spectrum, which also exhibits a mean heavy charge close to Z = 54. Surprisingly, the neutron even-odd effect of the light region is seen to be very close to the one in thermal neutron induced fission. The peak-to-valley ratio of the mass spectrum confirms that the mean excitation energy at fission is close to the expected one (14 MeV). The GEF code is used for comparison and always gives results very close to ours. (author) [fr

Fragment screening by SPR and advanced application to GPCRs.

Science.gov (United States)

Shepherd, Claire A; Hopkins, Andrew L; Navratilova, Iva

2014-01-01

Surface plasmon resonance (SPR) is one of the primary biophysical methods for the screening of low molecular weight 'fragment' libraries, due to its low protein consumption and 'label-free' methodology. SPR biosensor interaction analysis is employed to both screen and confirm the binding of compounds in fragment screening experiments, as it provides accurate information on the affinity and kinetics of molecular interactions. The most advanced application of the use of SPR for fragment screening is against membrane protein drug targets, such G-protein coupled receptors (GPCRs). Biophysical GPCR assays using SPR have been validated with pharmacological measurements approximate to cell-based methods, yet provide the advantage of biophysical methods in their ability to measure the weak affinities of low molecular weight fragments. A number of SPR fragment screens against GPCRs have now been disclosed in the literature. SPR fragment screening is proving versatile to screen both thermostabilised GPCRs and solubilised wild type receptors. In this chapter, we discuss the state-of-the-art in GPCR fragment screening by SPR and the technical considerations in performing such experiments. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multi-Stage System for Automatic Target Recognition

Science.gov (United States)

Chao, Tien-Hsin; Lu, Thomas T.; Ye, David; Edens, Weston; Johnson, Oliver

2010-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an

Leveraging structure determination with fragment screening for infectious disease drug targets: MECP synthase from Burkholderia pseudomallei

Energy Technology Data Exchange (ETDEWEB)

Begley, Darren W.; Hartley, Robert C.; Davies, Douglas R.; Edwards, Thomas E.; Leonard, Jess T.; Abendroth, Jan; Burris, Courtney A.; Bhandari, Janhavi; Myler, Peter J.; Staker, Bart L.; Stewart, Lance J. (UWASH); (Emerald)

2011-09-28

As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification of several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme.

Experimental and numerical studies of high-velocity impact fragmentation

Energy Technology Data Exchange (ETDEWEB)

Kipp, M.E.; Grady, D.E.; Swegle, J.W.

1993-08-01

Developments are reported in both experimental and numerical capabilities for characterizing the debris spray produced in penetration events. We have performed a series of high-velocity experiments specifically designed to examine the fragmentation of the projectile during impact. High-strength, well-characterized steel spheres (6.35 mm diameter) were launched with a two-stage light-gas gun to velocities in the range of 3 to 5 km/s. Normal impact with PMMA plates, thicknesses of 0.6 to 11 mm, applied impulsive loads of various amplitudes and durations to the steel sphere. Multiple flash radiography diagnostics and recovery techniques were used to assess size, velocity, trajectory and statistics of the impact-induced fragment debris. Damage modes to the primary target plate (plastic) and to a secondary target plate (aluminum) were also evaluated. Dynamic fragmentation theories, based on energy-balance principles, were used to evaluate local material deformation and fracture state information from CTH, a three-dimensional Eulerian solid dynamics shock wave propagation code. The local fragment characterization of the material defines a weighted fragment size distribution, and the sum of these distributions provides a composite particle size distribution for the steel sphere. The calculated axial and radial velocity changes agree well with experimental data, and the calculated fragment sizes are in qualitative agreement with the radiographic data. A secondary effort involved the experimental and computational analyses of normal and oblique copper ball impacts on steel target plates. High-resolution radiography and witness plate diagnostics provided impact motion and statistical fragment size data. CTH simulations were performed to test computational models and numerical methods.

Multi-Homologous Recombination-Based Gene Manipulation in the Rice Pathogen Fusarium fujikuroi

Directory of Open Access Journals (Sweden)

In Sun Hwang

2016-06-01

Full Text Available Gene disruption by homologous recombination is widely used to investigate and analyze the function of genes in Fusarium fujikuroi, a fungus that causes bakanae disease and root rot symptoms in rice. To generate gene deletion constructs, the use of conventional cloning methods, which rely on restriction enzymes and ligases, has had limited success due to a lack of unique restriction enzyme sites. Although strategies that avoid the use of restriction enzymes have been employed to overcome this issue, these methods require complicated PCR steps or are frequently inefficient. Here, we introduce a cloning system that utilizes multi-fragment assembly by In-Fusion to generate a gene disruption construct. This method utilizes DNA fragment fusion and requires only one PCR step and one reaction for construction. Using this strategy, a gene disruption construct for Fusarium cyclin C1 (FCC1 , which is associated with fumonisin B1 biosynthesis, was successfully created and used for fungal transformation. In vivo and in vitro experiments using confirmed fcc1 mutants suggest that fumonisin production is closely related to disease symptoms exhibited by F. fujikuroi strain B14. Taken together, this multi-fragment assembly method represents a simpler and a more convenient process for targeted gene disruption in fungi.

Fragment-based lead generation: identification of seed fragments by a highly efficient fragment screening technology

Science.gov (United States)

Neumann, Lars; Ritscher, Allegra; Müller, Gerhard; Hafenbradl, Doris

2009-08-01

For the detection of the precise and unambiguous binding of fragments to a specific binding site on the target protein, we have developed a novel reporter displacement binding assay technology. The application of this technology for the fragment screening as well as the fragment evolution process with a specific modelling based design strategy is demonstrated for inhibitors of the protein kinase p38alpha. In a fragment screening approach seed fragments were identified which were then used to build compounds from the deep-pocket towards the hinge binding area of the protein kinase p38alpha based on a modelling approach. BIRB796 was used as a blueprint for the alignment of the fragments. The fragment evolution of these deep-pocket binding fragments towards the fully optimized inhibitor BIRB796 included the modulation of the residence time as well as the affinity. The goal of our study was to evaluate the robustness and efficiency of our novel fragment screening technology at high fragment concentrations, compare the screening data with biochemical activity data and to demonstrate the evolution of the hit fragments with fast kinetics, into slow kinetic inhibitors in an in silico approach.

Fragmentation cross sections of relativistic 8436Kr and 10947Ag nuclei in targets from hydrogen to lead

International Nuclear Information System (INIS)

Nilsen, B.S.; Waddington, C.J.; Cummings, J.R.; Garrard, T.L.; Klarmann, J.

1995-01-01

With the addition of krypton and silver projectiles we have extended our previous studies of the fragmentation of heavy relativistic nuclei in targets ranging in mass from hydrogen to lead. These projectiles were studied at a number of discrete energies between 450 and 1500A MeV. The total and partial charge-changing cross sections were determined for each energy, target, and projectile, and the values compared with previous predictions. A new parametrization of the dependence of the total charge-changing cross sections on the target and projectile is introduced, based on nuclear charge radii derived from electron scattering. We have also parametrized the energy dependence of the total cross sections over the range of energies studied. New parameters were found for a previous representation of the partial charge-changing cross sections in hydrogen and a new parametrization has been introduced for the nonhydrogen targets. The evidence that limiting fragmentation has been attained for these relatively light projectile nuclei at Bevalac energies is shown to be inconclusive, and further measurements at higher energies will be needed to address this question

Mass distribution and multiple fragmentation events in high energy cluster-cluster collisions: evidence for a predicted phase transition

International Nuclear Information System (INIS)

Farizon, B.; Farizon, M.; Gaillard, M.J.; Genre, R.; Louc, S.; Martin, J.; Senn, G.; Scheier, P.; Maerk, T.D.

1996-09-01

Fragment size distributions including multiple fragmentation events have been measured for high energy H 25 + cluster ions (60 keV/amu) colliding with a neutral C 60 target. In contrast to earlier collision experiments with a helium target the present studies do not show a U-shaped fragment mass distribution, but a single power-law falloff with increasing fragment mass. This behaviour is similar to what is known for the intermediate regime in nuclear collision physics and thus confirms a recently predicted scaling from nuclear to molecular collisions

Multi-potent Natural Scaffolds Targeting Amyloid Cascade: In Search of Alzheimer's Disease Therapeutics.

Science.gov (United States)

Chakraborty, Sandipan

2017-01-01

Alzheimer's Disease (AD) once considered a rare disorder emerges as a major health concern in recent times. The disease pathogenesis is very complex and yet to be understood completely. However, "Amyloid Cascade" is the central event in disease pathogenesis. Several proteins of the amyloid cascade are currently being considered as potential targets for AD therapeutics discovery. Many potential compounds are in clinical trials, but till now there is no known cure for the disease. Recent years have witnessed remarkable research interest in the search of novel concepts in drug designing for AD. Multi-targeted ligand design is a paradigm shift in conventional drug discovery. In this process rather than designing ligands targeting a single receptor, novel ligands have been designed/ synthesized that can simultaneously target many pathways involved in disease pathogenesis. Here, recent developments in computational drug designing protocols to identify multi-targeted ligand for AD have been discussed. Therapeutic potential of different multi-potent compounds also has been discussed briefly. Prime emphasis has been given to multi-potent ligand from natural resources. Polyphenols are an interesting group of compounds which show efficacy against a wide range of disease and have the property to exhibit multi-potency. Several groups attempted to identify novel multi-potent phytochemicals for AD therapy. Multi-potency of several polyphenols or compounds synthesized using the poly-phenolic scaffolds have been briefly discussed here. However, the multi-targeted drug designing for AD is still in early stages, more advancement in drug designing method/algorithm developments is urgently required to discover more efficient compounds for AD therapeutics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

In silico design of fragment-based drug targeting host processing α-glucosidase i for dengue fever

Science.gov (United States)

Toepak, E. P.; Tambunan, U. S. F.

2017-02-01

Dengue is a major health problem in the tropical and sub-tropical regions. The development of antiviral that targeting dengue’s host enzyme can be more effective and efficient treatment than the viral enzyme. Host enzyme processing α-glucosidase I has an important role in the maturation process of dengue virus envelope glycoprotein. The inhibition of processing α-glucosidase I can become a promising target for dengue fever treatment. The antiviral approach using in silico fragment-based drug design can generate drug candidates with high binding affinity. In this research, 198.621 compounds were obtained from ZINC15 Biogenic Database. These compounds were screened to find the favorable fragments according to Rules of Three and pharmacological properties. The screening fragments were docked into the active site of processing α-glucosidase I. The potential fragment candidates from the molecular docking simulation were linked with castanospermine (CAST) to generate ligands with a better binding affinity. The Analysis of ligand - enzyme interaction showed ligands with code LRS 22, 28, and 47 have the better binding free energy than the standard ligand. Ligand LRS 28 (N-2-4-methyl-5-((1S,3S,6S,7R,8R,8aR)-1,6,7,8-tetrahydroxyoctahydroindolizin-3-yl) pentyl) indolin-1-yl) propionamide) itself among the other ligands has the lowest binding free energy. Pharmacological properties prediction also showed the ligands LRS 22, 28, and 47 can be promising as the dengue fever drug candidates.

An Automatic Multi-Target Independent Analysis Framework for Non-Planar Infrared-Visible Registration.

Science.gov (United States)

Sun, Xinglong; Xu, Tingfa; Zhang, Jizhou; Zhao, Zishu; Li, Yuankun

2017-07-26

In this paper, we propose a novel automatic multi-target registration framework for non-planar infrared-visible videos. Previous approaches usually analyzed multiple targets together and then estimated a global homography for the whole scene, however, these cannot achieve precise multi-target registration when the scenes are non-planar. Our framework is devoted to solving the problem using feature matching and multi-target tracking. The key idea is to analyze and register each target independently. We present a fast and robust feature matching strategy, where only the features on the corresponding foreground pairs are matched. Besides, new reservoirs based on the Gaussian criterion are created for all targets, and a multi-target tracking method is adopted to determine the relationships between the reservoirs and foreground blobs. With the matches in the corresponding reservoir, the homography of each target is computed according to its moving state. We tested our framework on both public near-planar and non-planar datasets. The results demonstrate that the proposed framework outperforms the state-of-the-art global registration method and the manual global registration matrix in all tested datasets.

Experiments for Multi-Stage Processes

DEFF Research Database (Denmark)

Tyssedal, John; Kulahci, Murat

2015-01-01

Multi-stage processes are very common in both process and manufacturing industries. In this article we present a methodology for designing experiments for multi-stage processes. Typically in these situations the design is expected to involve many factors from different stages. To minimize...... the required number of experimental runs, we suggest using mirror image pairs of experiments at each stage following the first. As the design criterion, we consider their projectivity and mainly focus on projectivity 3 designs. We provide the methodology for generating these designs for processes with any...

Experiences with Interactive Multi-touch Tables

Science.gov (United States)

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.

Chameleon fragmentation

Energy Technology Data Exchange (ETDEWEB)

Brax, Philippe [Institut de Physique Théorique, CEA, IPhT, CNRS, URA 2306, F-91191Gif/Yvette Cedex (France); Upadhye, Amol, E-mail: philippe.brax@cea.fr, E-mail: aupadhye@anl.gov [Institute for the Early Universe, Ewha University, International Education, Building #601, 11-1, Daehyun-Dong Seodaemun-Gu, Seoul 120-750 (Korea, Republic of)

2014-02-01

A scalar field dark energy candidate could couple to ordinary matter and photons, enabling its detection in laboratory experiments. Here we study the quantum properties of the chameleon field, one such dark energy candidate, in an ''afterglow'' experiment designed to produce, trap, and detect chameleon particles. In particular, we investigate the possible fragmentation of a beam of chameleon particles into multiple particle states due to the highly non-linear interaction terms in the chameleon Lagrangian. Fragmentation could weaken the constraints of an afterglow experiment by reducing the energy of the regenerated photons, but this energy reduction also provides a unique signature which could be detected by a properly-designed experiment. We show that constraints from the CHASE experiment are essentially unaffected by fragmentation for φ{sup 4} and 1/φ potentials, but are weakened for steeper potentials, and we discuss possible future afterglow experiments.

Chameleon fragmentation

International Nuclear Information System (INIS)

Brax, Philippe; Upadhye, Amol

2014-01-01

A scalar field dark energy candidate could couple to ordinary matter and photons, enabling its detection in laboratory experiments. Here we study the quantum properties of the chameleon field, one such dark energy candidate, in an ''afterglow'' experiment designed to produce, trap, and detect chameleon particles. In particular, we investigate the possible fragmentation of a beam of chameleon particles into multiple particle states due to the highly non-linear interaction terms in the chameleon Lagrangian. Fragmentation could weaken the constraints of an afterglow experiment by reducing the energy of the regenerated photons, but this energy reduction also provides a unique signature which could be detected by a properly-designed experiment. We show that constraints from the CHASE experiment are essentially unaffected by fragmentation for φ 4 and 1/φ potentials, but are weakened for steeper potentials, and we discuss possible future afterglow experiments

Use of the suprapatellar approach in intramedullary nailing of a multi-fragmentary dislocated tibia fracture with a hypermobile intermediate fragment in a young patient

Directory of Open Access Journals (Sweden)

Patrick Haubruck

2017-01-01

Full Text Available A case of an adolescent female patient who suffered from first grade open multi-fragment fracture of the tibia (AO42-C2 with a large hypermobile intermediate fragment is presented in this case report. Intramedullary nailing of the tibia remains the treatment of choice despite a high risk of malformation and anterior knee pain especially in multi-fragment fractures. Here the suprapatellar approach as a semiextended nailing technique seems favorable. The specialty in our case was an early change of procedures necessary due to persistent swelling during external fixation based on the hypermobile intermediate fragment. Decision in favor of this surgical technique was conducted in order to achieve beneficial alignment and union while protecting the softtissue despite the hypermobile intermediate fragment and decrease the risk of anterior knee pain. In our case we achieved successful alignment and proper bone healing without any signs of anterior knee pain or limitations in the range of motion of the knee. With this report we would like to recommend the suprapatellar approach as a favorable alternative in intramedullary nailing in this type of fracture also in young patients.

Timing characteristics of a two-dimensional multi-wire cathode strip detector for fission fragments

International Nuclear Information System (INIS)

Vind, R.P.; Joshi, B.N.; Jangale, R.V.; Inkar, A.L.; Prajapati, G.K.; John, B.V.; Biswas, D.C.

2014-01-01

In the recent past, a gas filled two-dimensional multi-wire cathode strip detector (MCSD) was developed for the detection of fission fragments (FFs). The position resolution was found to be about 1.0 and 1.5 mm in X and Y directions respectively. The detector has three electrode planes consisting of cathode strip (X-plane), anode wires and split-cathode wires (Y-plane). Each thin wire of the anode plane placed between the two cathode planes is essentially independent and behaves like a proportional counter. The construction of the detector in detail has been given in our earlier paper. The position information has been obtained by employing high impedance discrete delay line read out method for extracting position information in X and Y-directions. In this work, the timing characteristics of MCSD detector are reported to explore the possible use of this detector for the measurement of the mass of the fission fragments produced in heavy ion induced fission reactions

Non-extensive statistical aspects of clustering and nuclear multi-fragmentation

International Nuclear Information System (INIS)

Calboreanu, A.

2002-01-01

Recent developments concerning an application of the non-extensive Tsalis statistics to describe clustering phenomena is briefly presented. Cluster formation is a common feature of a large number of physical phenomena encountered in molecular and nuclear physics, astrophysics, condensed matter and biophysics. Common to all these is the large number of degrees of freedom, thus justifying a statistical approach. However the conventional statistical mechanics paradigm seems to fail in dealing with clustering. Whether this is due to the prevalence of complex dynamical constrains, or it is a manifestation of new statistics is a subject of considerable interest, which was intensively debated during the last few years. Tsalis conjecture has proved extremely appealing due to its rather elegant and transparent basic arguments. We present here evidence for its adequacy for the study of a large class of physical phenomena related to cluster formation. An application to nuclear multi-fragmentation is presented. (author)

Crawling and walking infants encounter objects differently in a multi-target environment.

Science.gov (United States)

Dosso, Jill A; Boudreau, J Paul

2014-10-01

From birth, infants move their bodies in order to obtain information and stimulation from their environment. Exploratory movements are important for the development of an infant's understanding of the world and are well established as being key to cognitive advances. Newly acquired motor skills increase the potential actions available to the infant. However, the way that infants employ potential actions in environments with multiple potential targets is undescribed. The current work investigated the target object selections of infants across a range of self-produced locomotor experience (11- to 14-month-old crawlers and walkers). Infants repeatedly accessed objects among pairs of objects differing in both distance and preference status, some requiring locomotion. Overall, their object actions were found to be sensitive to object preference status; however, the role of object distance in shaping object encounters was moderated by movement status. Crawlers' actions appeared opportunistic and were biased towards nearby objects while walkers' actions appeared intentional and were independent of object position. Moreover, walkers' movements favoured preferred objects more strongly for children with higher levels of self-produced locomotion experience. The multi-target experimental situation used in this work parallels conditions faced by foraging organisms, and infants' behaviours were discussed with respect to optimal foraging theory. There is a complex interplay between infants' agency, locomotor experience, and environment in shaping their motor actions. Infants' movements, in turn, determine the information and experiences offered to infants by their micro-environment.

Fragmentation of neck-like structures

International Nuclear Information System (INIS)

Montoya, C.; Bowman, D.R.; Peaslee, G.F.; Michigan State Univ., East Lansing, MI

1994-01-01

Evidence for intermediate mass fragment emission from neck-like structures joining projectile- and target-like residues has been observed for peripheral 129 Xe+ nat Cu collisions at E/A=50 MeV. These framents are emitted primarily at velocities intermediate between those of the projectile and the target. Relative to the charge distribution for fragments evaporated from the projectile-like residue, the distribution for ''neck'' emission shows an enhanced emission for fragments with 4 f < 8. (orig.)

'Multi-epitope-targeted' immune-specific therapy for a multiple sclerosis-like disease via engineered multi-epitope protein is superior to peptides.

Directory of Open Access Journals (Sweden)

Nathali Kaushansky

Full Text Available Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and "epitope spread", have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such "multi-epitope-targeting" approach in murine experimental autoimmune encephalomyelitis (EAE associated with a single ("classical" or multiple ("complex" anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as "multi-epitope-targeting" agents. Y-MSPc was superior to peptide(s in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells. Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of "classical" or "complex EAE" or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a "multi-epitope-targeting" strategy is required for

Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin.

Science.gov (United States)

Yuan, Zhi-xiang; Wu, Xiao-juan; Mo, Jingxin; Wang, Yan-li; Xu, Chao-qun; Lim, Lee Yong

2015-08-01

We have previously demonstrated that peptide fragments (PFs) of the human serum albumin could be developed as potential renal targeting carriers, in particular, the peptide fragment, PF-A299-585 (A299-585 representing the amino acid sequence of the human serum albumin). In this paper, we conjugated triptolide (TP), the anti-inflammatory Chinese traditional medicine, to PF-A299-585 via a succinic acid spacer to give TPS-PF-A299-585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A299-585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A299-585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labeled TPS-PF-A299-585. Renal targeting was confirmed in vivo in a membranous nephropathic (MN) rodent model, where optical imaging and analyses of biochemical markers were combined to show that TPS-PF-A299-585 was capable of alleviating the characteristic symptoms of MN. The collective data affirm PF-A299-585 to be a useful carrier for targeting TP to the kidney. Copyright © 2015 Elsevier B.V. All rights reserved.

EURISOL-DS Multi-MW Target Neutronic Calculations for the Baseline Configuration of the Multi-MW Target

CERN Document Server

Herrera-Martínez, A

2006-01-01

This document summarises the study performed within the Task #2 of the European Isotope Separation On-Line Radioactive Ion Beam Facility Design Study (EURISOL DS) [1] to design the Multi-MW proton-to-neutron converter. A preliminary study [2] was carried out in order to understand the nature of the interactions taking place in the proton-to-neutron converter and their impact on the design of the facility. Namely, the target dimensions and material composition, type of incident particle, its energy and the beam profile were analysed in the aforementioned technical note, and their optimum values were suggested in the conclusions. The present work is based on the results of the previous study and uses the same methodology, namely Monte Carlo simulations with FLUKA [3]. This note describes the performance of a Hg target design and addresses more detailed issues, such as the composition of the fission target and use of a neutron reflector. It also attempts to integrate those components together and estimate the wh...

Nuclear fragmentation and the number of particle tracks in tissue

International Nuclear Information System (INIS)

Ponomarev, A. L.; Cucinotta, F. A.

2006-01-01

For high energy nuclei, the number of particle tracks per cell is modified by local nuclear reactions that occur, with large fluctuations expected for heavy ion tracks. Cells near the interaction site of a reaction will experience a much higher number of tracks than estimated by the average fluence. Two types of reaction products are possible and occur in coincidence; projectile fragments, which generally have smaller charge and similar velocity to that of the projectile, and target fragments, which are produced from the fragmentation of the nuclei of water atoms or other cellular constituents with low velocity. In order to understand the role of fragmentation in biological damage a new model of human tissue irradiated by heavy ions was developed. A box of the tissue is modelled with periodic boundary conditions imposed, which extrapolates the technique to macroscopic volumes of tissue. The cross sections for projectile and target fragmentation products are taken from the quantum multiple scattering fragmentation code previously developed at NASA Johnson Space Center. Statistics of fragmentation pathways occurring in a cell monolayer, as well as in a small volume of 10 x 10 x 10 cells are given. A discussion on approaches to extend the model to describe spatial distributions of inactivated or other cell damage types, as well as highly organised tissues of multiple cell types, is presented. (authors)

Fragmentation and direct transfer reactions for 40Ar incident beam on 27Al target at 1760 MeV

International Nuclear Information System (INIS)

Cisse, Ousmane

1985-01-01

Peripheral collision studies performed with 40 Ar projectiles at 44 MeV/A and 27 Al target show that both fragmentation and transfer reactions can be discerned in this type of interaction. The experimental observation of fragments with masses charges and velocities close to those of the incident beam are the signature of transfer reactions and a detailed analysis of the energy spectra of such fragments has been carried out and interpreted in terms of a direct diffraction transfer model. On the other hand, for large mass transfer reactions, abrasion is the suitable mechanism. Inclusive fragment measurement together with the appropriate residual nuclei-fragment coincidence results then provides experimental data in good agreement with the theoretical predictions obtained from a participant spectator model. These investigations also indicate that the separation energies of the participant from the spectator nucleus, at least within the framework of the above model, can be interpreted in terms of a friction force which becomes more efficient as the projectile energy decreases. (author) [fr

Multi-MW target station: Beam Window Issues and Transverse Film Target

CERN Document Server

Herrera-Martinez, A

The analysis of the EURISOL-DS Multi_MW target precise geometry has proved that large fission yields can be achieved with a 4 MW, providing a technically feasible design to evacuate the power deposited in the liquid mercury. Different designs for the mercury flow have been proposed, which maintain its temperature below the boiling point with moderate flow speeds (maximum 4 m/s).

TALE nickase mediates high efficient targeted transgene integration at the human multi-copy ribosomal DNA locus.

Science.gov (United States)

Wu, Yong; Gao, Tieli; Wang, Xiaolin; Hu, Youjin; Hu, Xuyun; Hu, Zhiqing; Pang, Jialun; Li, Zhuo; Xue, Jinfeng; Feng, Mai; Wu, Lingqian; Liang, Desheng

2014-03-28

Although targeted gene addition could be stimulated strikingly by a DNA double strand break (DSB) created by either zinc finger nucleases (ZFNs) or TALE nucleases (TALENs), the DSBs are really mutagenic and toxic to human cells. As a compromised solution, DNA single-strand break (SSB) or nick has been reported to mediate high efficient gene addition but with marked reduction of random mutagenesis. We previously demonstrated effective targeted gene addition at the human multicopy ribosomal DNA (rDNA) locus, a genomic safe harbor for the transgene with therapeutic potential. To improve the transgene integration efficiency by using TALENs while lowering the cytotoxicity of DSBs, we created both TALENs and TALE nickases (TALENickases) targeting this multicopy locus. A targeting vector which could integrate a GFP cassette at the rDNA locus was constructed and co-transfected with TALENs or TALENickases. Although the fraction of GFP positive cells using TALENs was greater than that using TALENickases during the first few days after transfection, it reduced to a level less than that using TALENickases after continuous culture. Our findings showed that the TALENickases were more effective than their TALEN counterparts at the multi-copy rDNA locus, though earlier studies using ZFNs and ZFNickases targeting the single-copy loci showed the reverse. Besides, TALENickases mediated the targeted integration of a 5.4 kb fragment at a frequency of up to 0.62% in HT1080 cells after drug selection, suggesting their potential application in targeted gene modification not being limited at the rDNA locus. Copyright © 2014 Elsevier Inc. All rights reserved.

Angular distributions of target fragments from the reactions of 292 MeV - 25.2 GeV 12C with 197Au and 238U

International Nuclear Information System (INIS)

Morita, Y.

1983-01-01

The angular distributions of the 197 Au target fragments were all forwardly peaked. Extensively forward peaked angular distributions were observed at the non-relativistic projectile energies (292 MeV, 1.0 GeV). No obvious differences were observed in the angular distributions at the different relativistic projectile energies of 3.0 GeV, 12.0 GeV and 25.2 GeV. The characteristic angular distribution pattern from the relativistic projectile energy experiments was also observed in the non-relativistic energy experiments. Maximum degree of forward-peaking in the angular distributions at each projectile energy was observed at the product mass number (A) around 190 from the 292 MeV projectile energy, at A = 180 from 1.0 GeV and at A =175 from 3.0 GeV and 12.0 GeV. In general, two different types of angular distributions were observed in the relativistic projectile energy experiments with the 238 U target. Isotropic angular distributions were observed for the fission product nuclides. The angular distributions of the fission products at the intermediate (292 MeV) energy showed slightly forward peaked angular distributions. Because of the long projectile-target interaction time in the primary nuclear reaction, larger momentum was transferred from the projectile to the target nucleus. Steep forward-peaked angular distributions were also observed with the 238 U target

Target-fragment angular distributions for the interaction of 86 MeV/A 12C with 197Au

International Nuclear Information System (INIS)

Kraus, R.H. Jr.; Loveland, W.; McGaughey, P.L.; Seaborg, G.T.; Morita, Y.; Hageboe, E.; Haldorsen, I.R.; Sugihara, T.T.

1985-01-01

Target-fragment angular distributions were measured using radiochemical techniques for 69 different fragments (44 12 C with 197 Au. The angular distributions in the laboratory system are forward-peaked with some distributions also showing a backward peaking. The shapes of the laboratory system distributions were compared with the predictions of the nuclear firestreak model. The measured angular distributions differed markedly from the predictions of the firestreak model in most cases. This discrepancy could be due, in part, to overestimation of the transferred longitudinal momentum by the firestreak model, the assumption of isotropic angular distributions for fission and particle emission in the moving frame and incorrect assumptions about how the lightest (A 145) fragment distributions were symmetric about 90 0 . (orig.)

High energy collisions of nuclei: experiments

International Nuclear Information System (INIS)

Heckman, H.H.

1977-09-01

Heavy-ion nuclear reactions with projectile energies up to 2.1 GeV/A are reviewed. The concept of ''rapidity'' is elucidated, and the reactions discussed are divided into sections dealing with target fragmentation, projectile fragmentation, and the intermediate region, with emphasis on the production of light nuclei in high-energy heavy-ion collisions. Target fragmentation experiments using nuclear emulsion and AgCl visual track detectors are also summarized. 18 figures

Robust Target Tracking with Multi-Static Sensors under Insufficient TDOA Information.

Science.gov (United States)

Shin, Hyunhak; Ku, Bonhwa; Nelson, Jill K; Ko, Hanseok

2018-05-08

This paper focuses on underwater target tracking based on a multi-static sonar network composed of passive sonobuoys and an active ping. In the multi-static sonar network, the location of the target can be estimated using TDOA (Time Difference of Arrival) measurements. However, since the sensor network may obtain insufficient and inaccurate TDOA measurements due to ambient noise and other harsh underwater conditions, target tracking performance can be significantly degraded. We propose a robust target tracking algorithm designed to operate in such a scenario. First, track management with track splitting is applied to reduce performance degradation caused by insufficient measurements. Second, a target location is estimated by a fusion of multiple TDOA measurements using a Gaussian Mixture Model (GMM). In addition, the target trajectory is refined by conducting a stack-based data association method based on multiple-frames measurements in order to more accurately estimate target trajectory. The effectiveness of the proposed method is verified through simulations.

Fragmentation processes in nuclear reactions

International Nuclear Information System (INIS)

Legrain, R.

1984-08-01

Projectile and nuclear fragmentation are defined and processes referred to are recalled. The two different aspects of fragmentation are considered but the emphasis is also put on heavy ion induced reactions. The preliminary results of an experiment performed at GANIL to study peripheral heavy ions induced reactions at intermediate energy are presented. The results of this experiment will illustrate the characteristics of projectile fragmentation and this will also give the opportunity to study projectile fragmentation in the transition region. Then nuclear fragmentation is considered which is associated with more central collisions in the case of heavy ion induced reactions. This aspect of fragmentation is also ilustrated with two heavy ion experiments in which fragments emitted at large angle have been observed

Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy

Directory of Open Access Journals (Sweden)

Shan L

2015-09-01

Full Text Available Lingling Shan,1 Ming Liu,2 Chao Wu,1 Liang Zhao,1 Siwen Li,3 Lisheng Xu,1 Wengen Cao,1 Guizhen Gao,1 Yueqing Gu3 1Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, People’s Republic of China; 2Department of Biology, University of South Dakota, Vermillion, SD, USA; 3Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In response to the challenges of cancer chemotherapeutics, including poor physicochemical properties, low tumor targeting ability, and harmful side effects, we developed a new tumor-targeted multi-small molecule drug delivery platform. Using paclitaxel (PTX as a model therapeutic, we prepared two prodrugs, ie, folic acid-fluorescein-5(6-isothiocyanate-arginine-paclitaxel (FA-FITC-Arg-PTX and folic acid-5-aminofluorescein-glutamic-paclitaxel (FA-5AF-Glu-PTX, composed of folic acid (FA, target, amino acids (Arg or Glu, linker, and fluorescent dye (fluorescein in vitro or near-infrared fluorescent dye in vivo in order to better understand the mechanism of PTX prodrug targeting. In vitro and acute toxicity studies demonstrated the low toxicity of the prodrug formulations compared with the free drug. In vitro and in vivo studies indicated that folate receptor-mediated uptake of PTX-conjugated multi-small molecule carriers induced high antitumor activity. Notably, compared with free PTX and with PTX-loaded macromolecular carriers from our previous study, this multi-small molecule-conjugated strategy improved the water solubility, loading rate, targeting ability, antitumor activity, and toxicity profile of PTX. These results support the use of multi-small molecules as tumor-targeting drug delivery systems. Keywords: multi-small molecules, paclitaxel, prodrugs, targeting, tumor therapy

Fragment emission in reactions of 18.5-GeV 12C ions with complex nuclei

International Nuclear Information System (INIS)

Porile, N.T.; Cole, G.D.

1982-01-01

The emission of fragments ranging from 24 Na to 52 Mn in reactions of 18.5 GeV 12 C ions with Cu, Ag, Gd, Ta, Au, and U targets has been studied by means of activation techniques. The experiments involved determination of the fragment production cross sections and thick-target recoil properties. The latter were used to obtain mean fragment kinetic energies and values of β/sub parallel to/, the forward velocity component of the struck nucleus (in units of c). The results are compared with similar data for incident protons of the same total kinetic energy. The data may be used to assess the importance of central collisions in fragment production. Such collisions lead to the near total destruction of both interacting nuclei and the resulting fragments are emitted by a system of intermediate rapidity. In such a process, the factorization hypothesis, which has been shown to be valid for target and projectile fragmentation reactions, should not be obeyed. A test for factorization is performed by means of a relation which states that the ratio of the cross sections for producing fragment /sup A/Z in 12 C reactions to that for producing the same fragment in proton reactions with the same target is unity, provided both cross sections are reduced by the values of the corresponding total reaction cross sections sigma/sub R/, and evaluated for the same total kinetic energy of the projectile. The results of this comparison for the targets studied are presented and discussed

THE ROLE OF PEBBLE FRAGMENTATION IN PLANETESIMAL FORMATION. I. EXPERIMENTAL STUDY

Energy Technology Data Exchange (ETDEWEB)

Syed, M. Bukhari; Blum, J. [Institut für Geophysik und extraterrestrische Physik, Technische Universität zu Braunschweig, Mendelssohnstr. 3, D-38106 Braunschweig (Germany); Jansson, K. Wahlberg; Johansen, A. [Lund Observatory, Department of Astronomy and Theoretical Physics, Lund University, Box 43, SE-221 00 Lund (Sweden)

2017-01-10

Previous work on protoplanetary dust growth shows a halt at centimeter sizes owing to the occurrence of bouncing at velocities of ≳0.1 m s{sup −1} and fragmentation at velocities ≳1 m s{sup −1}. To overcome these barriers, spatial concentration of centimeter-sized dust pebbles and subsequent gravitational collapse have been proposed. However, numerical investigations have shown that dust aggregates may undergo fragmentation during the gravitational collapse phase. This fragmentation in turn changes the size distribution of the solids and thus must be taken into account in order to understand the properties of the planetesimals that form. To explore the fate of dust pebbles undergoing fragmenting collisions, we conducted laboratory experiments on dust-aggregate collisions with a focus on establishing a collision model for this stage of planetesimal formation. In our experiments, we analyzed collisions of dust aggregates with masses between 0.7 and 91 g mass ratios between target and projectile from 1 to 126 at a fixed porosity of 65%, within the velocity range of 1.5–8.7 m s{sup −1}, at low atmospheric pressure of ∼10{sup −3} mbar, and in free-fall conditions. We derived the mass of the largest fragment, the fragment size/mass distribution, and the efficiency of mass transfer as a function of collision velocity and projectile/target aggregate size. Moreover, we give recipes for an easy-to-use fragmentation and mass-transfer model for further use in modeling work. In a companion paper, we use the experimental findings and the derived dust-aggregate collision model to investigate the fate of dust pebbles during gravitational collapse.

Identifying natural compounds as multi-target-directed ligands against Alzheimer's disease: an in silico approach.

Science.gov (United States)

Ambure, Pravin; Bhat, Jyotsna; Puzyn, Tomasz; Roy, Kunal

2018-04-23

Alzheimer's disease (AD) is a multi-factorial disease, which can be simply outlined as an irreversible and progressive neurodegenerative disorder with an unclear root cause. It is a major cause of dementia in old aged people. In the present study, utilizing the structural and biological activity information of ligands for five important and mostly studied vital targets (i.e. cyclin-dependant kinase 5, β-secretase, monoamine oxidase B, glycogen synthase kinase 3β, acetylcholinesterase) that are believed to be effective against AD, we have developed five classification models using linear discriminant analysis (LDA) technique. Considering the importance of data curation, we have given more attention towards the chemical and biological data curation, which is a difficult task especially in case of big data-sets. Thus, to ease the curation process we have designed Konstanz Information Miner (KNIME) workflows, which are made available at http://teqip.jdvu.ac.in/QSAR_Tools/ . The developed models were appropriately validated based on the predictions for experiment derived data from test sets, as well as true external set compounds including known multi-target compounds. The domain of applicability for each classification model was checked based on a confidence estimation approach. Further, these validated models were employed for screening of natural compounds collected from the InterBioScreen natural database ( https://www.ibscreen.com/natural-compounds ). Further, the natural compounds that were categorized as 'actives' in at least two classification models out of five developed models were considered as multi-target leads, and these compounds were further screened using the drug-like filter, molecular docking technique and then thoroughly analyzed using molecular dynamics studies. Finally, the most potential multi-target natural compounds against AD are suggested.

A modified high-intensity Cs sputter negative-ion source with multi-target mechanism

International Nuclear Information System (INIS)

Si Houzhi; Zhang Weizhong; Zhu Jinhau; Du Guangtian; Zhang Tiaorong; Gao Xiang

1993-01-01

The source is based on Middleton's high-intensity mode, but modified to a multi-target version. It is equipped with a spherical molybdenum ionizer, a 20-position target wheel and a vacuum lock for loading and unloading sample batches. A metal-ceramic bonded section protected by a specially designed labyrinth shielding system results in reliable insulation of the cathode and convenient control of cesium vapor. The latter is particularly important when an oversupply of cesium occurs. The source was developed for accelerator mass spectrometry (AMS) applications. Recently, three versions based on the prototype of the source have been successfully tested to meet different requirements: (a) Single target version, (b) multi-target version with manual sample change, and (c) multi-target version with remote control sample change. Some details of the technical and operational characteristics are presented. (orig.)

Study of fission fragments produced by 14N + 235U reaction

International Nuclear Information System (INIS)

Yalcinkaya, M.; Erduran, M.N.; Ganioglu, E.; Akkus, B.; Bostan, M.; Gurdal, G.; Erturk, S.; Balabanski, D.; Minkova, A.; Danchev, M.

2005-01-01

This work was performed to understand the structure of neutron rich fission fragments around ∼ 130 region. A thin metallic 235 U target was bombarded by 14 N beam with 10 MeV/A from the Separated Sector Cyclotron at the National Accelerator Centre, Cape Town, South Africa. The main goal to detect and identify fission fragments and to obtain their mass distribution was achieved by using Solar Cell detectors in the AFRODITE (African Omnipurpose Detector for Innovative Techniques and Experiments) spectrometer. The X-rays emitted from fission fragments were detected by LEP detectors and γ rays emitted from excited states of the fission fragments were detected by CLOVER detectors in the spectrometer. (author)

Timeframe Dependent Fragment Ions Observed in In-Source Decay Experiments with β-Casein Using MALDI MS.

Science.gov (United States)

Sekiya, Sadanori; Nagoshi, Keishiro; Iwamoto, Shinichi; Tanaka, Koichi; Takayama, Mitsuo

2015-09-01

The fragment ions observed with time-of-flight (TOF) and quadrupole ion trap (QIT) TOF mass spectrometers (MS) combined with matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) experiments of phosphorylated analytes β-casein and its model peptide were compared from the standpoint of the residence timeframe of analyte and fragment ions in the MALDI ion source and QIT cell. The QIT-TOF MS gave fragment c-, z'-, z-ANL, y-, and b-ions, and further degraded fragments originating from the loss of neutrals such as H(2)O, NH(3), CH(2)O (from serine), C2H4O (from threonine), and H(3)PO(4), whereas the TOF MS merely showed MALDI source-generated fragment c-, z'-, z-ANL, y-, and w-ions. The fragment ions observed in the QIT-TOF MS could be explained by the injection of the source-generated ions into the QIT cell or a cooperative effect of a little internal energy deposition, a long residence timeframe (140 ms) in the QIT cell, and specific amino acid effects on low-energy CID, whereas the source-generated fragments (c-, z'-, z-ANL, y-, and w-ions) could be a result of prompt radical-initiated fragmentation of hydrogen-abundant radical ions [M + H + H](+) and [M + H - H](-) within the 53 ns timeframe, which corresponds to the delayed extraction time. The further degraded fragment b/y-ions produced in the QIT cell were confirmed by positive- and negative-ion low-energy CID experiments performed on the source-generated ions (c-, z'-, and y-ions). The loss of phosphoric acid (98 u) from analyte and fragment ions can be explained by a slow ergodic fragmentation independent of positive and negative charges.

Timeframe Dependent Fragment Ions Observed in In-Source Decay Experiments with β-Casein Using MALDI MS

Science.gov (United States)

Sekiya, Sadanori; Nagoshi, Keishiro; Iwamoto, Shinichi; Tanaka, Koichi; Takayama, Mitsuo

2015-09-01

The fragment ions observed with time-of-flight (TOF) and quadrupole ion trap (QIT) TOF mass spectrometers (MS) combined with matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) experiments of phosphorylated analytes β-casein and its model peptide were compared from the standpoint of the residence timeframe of analyte and fragment ions in the MALDI ion source and QIT cell. The QIT-TOF MS gave fragment c-, z'-, z-ANL, y-, and b-ions, and further degraded fragments originating from the loss of neutrals such as H2O, NH3, CH2O (from serine), C2H4O (from threonine), and H3PO4, whereas the TOF MS merely showed MALDI source-generated fragment c-, z'-, z-ANL, y-, and w-ions. The fragment ions observed in the QIT-TOF MS could be explained by the injection of the source-generated ions into the QIT cell or a cooperative effect of a little internal energy deposition, a long residence timeframe (140 ms) in the QIT cell, and specific amino acid effects on low-energy CID, whereas the source-generated fragments (c-, z'-, z-ANL, y-, and w-ions) could be a result of prompt radical-initiated fragmentation of hydrogen-abundant radical ions [M + H + H]+ and [M + H - H]- within the 53 ns timeframe, which corresponds to the delayed extraction time. The further degraded fragment b/y-ions produced in the QIT cell were confirmed by positive- and negative-ion low-energy CID experiments performed on the source-generated ions (c-, z'-, and y-ions). The loss of phosphoric acid (98 u) from analyte and fragment ions can be explained by a slow ergodic fragmentation independent of positive and negative charges.

SOFIA: An innovative setup to measure complete isotopic yield of fission fragments

Directory of Open Access Journals (Sweden)

Pellereau E.

2013-12-01

Full Text Available We performed an experiment dedicated to the accurate isotopic yield measurement of fission fragments over the whole range. SOFIA exploits the inverse kinematics technique: using heavy ion beams at relativistic energies, fission is induced by Coulomb excitation in a high-Z target. The fragments are emitted forward and both of them are identified in charge and mass. The setup will be presented, as well as preliminary spectra.

Fragmentation of the C60 molecule in collision with light ions studied by a multi-correlation technique. Cross-sections, electron spectroscopy; Fragmentation de la molecule C60 par impact d'ions legers etudiee en multicorrelation. Sections efficaces, spectroscopie d'electrons

Energy Technology Data Exchange (ETDEWEB)

Rentenier, A

2004-04-01

A quantitative study of the C60 fullerenes fragmentation in collision with light ions (H{sub n}{sup +} with n=1,2,3, He{sup q+} with q=1,2) in the velocity range 0,1 - 2,3 u.a.) is presented. The multi-correlation technique, developed between fragment ions and electrons with well defined energy, has enlightened some of the dependences and properties of fragmentation mechanisms (cross sections, electron spectroscopy, size distributions, kinetic energy of fragment ions, Campi's scatter plot, activation energies). The deposited energy hence appeared as an important parameter. Cross sections have been measured, for the first time, for all the collisional processes. Ionisation and capture only depends on the collision velocity. On the other hand, scaling laws with the deposited energy have been observed for the cross sections of multifragmentation, which depends on the collision energy and the nature of the projectile. The deposited energy has also been found as an essential parameter to understand the evolution of the charged fragment size distributions. The electron spectroscopy, achieved at an emission angle of 35 degrees, showed spectra peaked at important energies (from 5 to 20 eV). The spectra shape depends on the collision velocity. A first theoretical analysis points out the link between the observed energy distribution and the presence of a centrifugal potential barrier. Finally, correlation experiments between produced ions and electron energy reveal that electron energy increases with internal energy. (author)

Heavy quarks fragmentation in charmed mesons in DELPHI experiment at LEP

International Nuclear Information System (INIS)

Levy, J.M.

1994-04-01

With the big statistics expected at LEP, the electroweak sector of the Standard Model can be tested as well as the theory of strong interactions. Quantum Chromo-Dynamics is indeed predictive for quarks properties, but does not explain how quarks fragment into hadrons. So far the hadronization can only be described with phenomenological models. The work presented in this thesis was performed on the DELPHI experiment at LEP and concerns the production and the fragmentation of heavy quarks into charmed mesons D , D* and D**. With the whole statistics of 1991 and 1992 (1 013 300 hadronic decays of the Z), more than 4500 charmed mesons decays have been reconstructed in the channels D 0 → K - π + , D + → K - π + π+ and D * +→ D 0 π + followed by D 0 → K - π + . Using also 1993 data and the channel D 0 → K - π + π + π - , evidence for D** production is presented. For the first time, the production rate is measured for each D meson separately for cc and bb contributions. In fact, D mesons can be produced either directly from the fragmentation of c quark or un-directly from the fragmentation of b quark into B mesons which decay into D mesons. (authors). 120 refs

Skin-Derived C-Terminal Filaggrin-2 Fragments Are Pseudomonas aeruginosa-Directed Antimicrobials Targeting Bacterial Replication.

Directory of Open Access Journals (Sweden)

Britta Hansmann

2015-09-01

Full Text Available Soil- and waterborne bacteria such as Pseudomonas aeruginosa are constantly challenging body surfaces. Since infections of healthy skin are unexpectedly rare, we hypothesized that the outermost epidermis, the stratum corneum, and sweat glands directly control the growth of P. aeruginosa by surface-provided antimicrobials. Due to its high abundance in the upper epidermis and eccrine sweat glands, filaggrin-2 (FLG2, a water-insoluble 248 kDa S100 fused-type protein, might possess these innate effector functions. Indeed, recombinant FLG2 C-terminal protein fragments display potent antimicrobial activity against P. aeruginosa and other Pseudomonads. Moreover, upon cultivation on stratum corneum, P. aeruginosa release FLG2 C-terminus-containing FLG2 fragments from insoluble material, indicating liberation of antimicrobially active FLG2 fragments by the bacteria themselves. Analyses of the underlying antimicrobial mechanism reveal that FLG2 C-terminal fragments do not induce pore formation, as known for many other antimicrobial peptides, but membrane blebbing, suggesting an alternative mode of action. The association of the FLG2 fragment with the inner membrane of treated bacteria and its DNA-binding implicated an interference with the bacterial replication that was confirmed by in vitro and in vivo replication assays. Probably through in situ-activation by soil- and waterborne bacteria such as Pseudomonads, FLG2 interferes with the bacterial replication, terminates their growth on skin surface and thus may contributes to the skin's antimicrobial defense shield. The apparent absence of FLG2 at certain body surfaces, as in the lung or of burned skin, would explain their higher susceptibility towards Pseudomonas infections and make FLG2 C-terminal fragments and their derivatives candidates for new Pseudomonas-targeting antimicrobials.

Skin-Derived C-Terminal Filaggrin-2 Fragments Are Pseudomonas aeruginosa-Directed Antimicrobials Targeting Bacterial Replication.

Science.gov (United States)

Hansmann, Britta; Schröder, Jens-Michael; Gerstel, Ulrich

2015-09-01

Soil- and waterborne bacteria such as Pseudomonas aeruginosa are constantly challenging body surfaces. Since infections of healthy skin are unexpectedly rare, we hypothesized that the outermost epidermis, the stratum corneum, and sweat glands directly control the growth of P. aeruginosa by surface-provided antimicrobials. Due to its high abundance in the upper epidermis and eccrine sweat glands, filaggrin-2 (FLG2), a water-insoluble 248 kDa S100 fused-type protein, might possess these innate effector functions. Indeed, recombinant FLG2 C-terminal protein fragments display potent antimicrobial activity against P. aeruginosa and other Pseudomonads. Moreover, upon cultivation on stratum corneum, P. aeruginosa release FLG2 C-terminus-containing FLG2 fragments from insoluble material, indicating liberation of antimicrobially active FLG2 fragments by the bacteria themselves. Analyses of the underlying antimicrobial mechanism reveal that FLG2 C-terminal fragments do not induce pore formation, as known for many other antimicrobial peptides, but membrane blebbing, suggesting an alternative mode of action. The association of the FLG2 fragment with the inner membrane of treated bacteria and its DNA-binding implicated an interference with the bacterial replication that was confirmed by in vitro and in vivo replication assays. Probably through in situ-activation by soil- and waterborne bacteria such as Pseudomonads, FLG2 interferes with the bacterial replication, terminates their growth on skin surface and thus may contributes to the skin's antimicrobial defense shield. The apparent absence of FLG2 at certain body surfaces, as in the lung or of burned skin, would explain their higher susceptibility towards Pseudomonas infections and make FLG2 C-terminal fragments and their derivatives candidates for new Pseudomonas-targeting antimicrobials.

Numerical-experiment investigation of coalescence of gaseous protogalactic fragments in triple systems

International Nuclear Information System (INIS)

Kiseleva, L.G.; Orlov, V.V.

1988-01-01

The numerical-experiment approach in the framework of the general gravitational three-body problem has been used to investigate the dynamical evolution of triple systems of gaseous protogalactic fragments. The masses of the fragments are equal, the initial velocities zero. The initial positions were specified by uniform scanning in the region D of all possible initial configurations. Calculations were continued until the first two-body encounter of the fragments. Different values of the fragment radii at this times were considered, namely, r in the interval [0.001, 0.1]d, where d is the mean diameter of the system. It is shown that for such r the pair of gaseous fragments coalesces in the majority of cases (from 50.2% for r = 0.001d to 96.7% for r = 0.1d). The mean specific angular momentum of their relative motion, which becomes spin angular momentum of the coalescence product, is (0.8 +- 1.0)/centered dot/10 29 /root/μl cm 2 sec for the most probable value r = 10l kpc (the masses of the fragments are 5/centered dot/10 10 μM/circled dot/; l and μ are scale factors), this agreeing in order of magnitude with the specific angular momenta of disk galaxies if l, μ /approximately/ 1. For each value of r, a continuous zone of initial configurations corresponding to coalescences is identified in the region D

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

Science.gov (United States)

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.

Fragment-based approaches to TB drugs.

Science.gov (United States)

Marchetti, Chiara; Chan, Daniel S H; Coyne, Anthony G; Abell, Chris

2018-02-01

Tuberculosis is an infectious disease associated with significant mortality and morbidity worldwide, particularly in developing countries. The rise of antibiotic resistance in Mycobacterium tuberculosis (Mtb) urgently demands the development of new drug leads to tackle resistant strains. Fragment-based methods have recently emerged at the forefront of pharmaceutical development as a means to generate more effective lead structures, via the identification of fragment molecules that form weak but high quality interactions with the target biomolecule and subsequent fragment optimization. This review highlights a number of novel inhibitors of Mtb targets that have been developed through fragment-based approaches in recent years.

Triggered fragmentation experiment with sodium, silicone oil and pentane

International Nuclear Information System (INIS)

Morita, T.

1990-12-01

Within the analysis of severe hypothetical fast breeder accidents the consequences of a fuel-coolant-interaction have to be considered, i.e. the thermal interaction between hot molten fuel and sodium. For the detailed understanding of the fragmentation during the thermal interaction of a hot liquid droplet with a cold fluid series of experiments were performed with sodium and solicone oil as hot liquid and pentane as cold easily volatile fluid. For the precise observation of the reaction an efficient high speed camera with a maximum recording frequency of 1x105 f/s was used. So the fragmentation caused by boiling phenomena could be observed. The pictures were used to estimate quantitatively e.g. the volume of the reaction zone and its expansion rate. By a special measuring device for the first time results on the time dependent portion of the liquid within the reaction zone could be gained. Based on the measured results of the experiments the course of a typical reaction, which can be devided into six phases, is presented and physically explained in this report. The influence of experimental parameters, as pressure of the external trigger and temperature of the hot liquid droplet, was investigated and from this the role of the homogeneous nucleation temperature and the external trigger for the reaction was deduced. (orig.) [de

Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.

Science.gov (United States)

Huschmann, Franziska U; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S; Mueller, Uwe

2016-05-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin-fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity.

Structures of endothiapepsin–fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library

Science.gov (United States)

Huschmann, Franziska U.; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S.; Mueller, Uwe

2016-01-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein–ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin–fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity. PMID:27139825

Effects of target plasma electron-electron collisions on correlated motion of fragmented H2+ protons

International Nuclear Information System (INIS)

Barriga-Carrasco, Manuel D.

2006-01-01

The objective of the present work is to examined the effects of plasma target electron-electron collisions on H 2 + protons traversing it. Specifically, the target is deuterium in a plasma state with temperature T e =10 eV and density n=10 23 cm -3 , and proton velocities are v p =v th , v p =2v th , and v p =3v th , where v th is the electron thermal velocity of the target plasma. Proton interactions with plasma electrons are treated by means of the dielectric formalism. The interactions among close protons through plasma electronic medium are called vicinage forces. It is checked that these forces always screen the Coulomb explosions of the two fragmented protons from the same H 2 + ion decreasing their relative distance. They also align the interproton vector along the motion direction, and increase the energy loss of the two protons at early dwell times while for longer times the energy loss tends to the value of two isolated protons. Nevertheless, vicinage forces and effects are modified by the target electron collisions. These collisions enhance the calculated self-stopping and vicinage forces over the collisionless results. Regarding proton correlated motion, when these collisions are included, the interproton vector along the motion direction overaligns at slower proton velocities (v p =v th ) and misaligns for faster ones (v p =2v th , v p =3v th ). They also contribute to a great extend to increase the energy loss of the fragmented H 2 + ion. This later effect is more significant in reducing projectile velocity

Effective progression of nuclear magnetic resonance-detected fragment hits.

Science.gov (United States)

Eaton, Hugh L; Wyss, Daniel F

2011-01-01

Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade as an alternate lead generation tool to HTS approaches. Several compounds have now progressed into the clinic which originated from a fragment-based approach, demonstrating the utility of this emerging field. While fragment hit identification has become much more routine and may involve different screening approaches, the efficient progression of fragment hits into quality lead series may still present a major bottleneck for the broadly successful application of FBDD. In our laboratory, we have extensive experience in fragment-based NMR screening (SbN) and the subsequent iterative progression of fragment hits using structure-assisted chemistry. To maximize impact, we have applied this approach strategically to early- and high-priority targets, and those struggling for leads. Its application has yielded a clinical candidate for BACE1 and lead series in about one third of the SbN/FBDD projects. In this chapter, we will give an overview of our strategy and focus our discussion on NMR-based FBDD approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact fragmentation of a brittle metal compact

Science.gov (United States)

Tang, Megan; Hooper, Joseph P.

2018-05-01

The fragmentation behavior of a metal powder compact which is ductile in compression but brittle in tension is studied via impact experiments and analytical models. Consolidated metal compacts were prepared via cold-isostatic pressing of powder at 380 MPa followed by moderate annealing at 365 °C. The resulting zinc material is ductile and strain-hardening in high-rate uniaxial compression like a traditional metal, but is elastic-brittle in tension with a fracture toughness comparable to a ceramic. Cylindrical samples were launched up to 800 m/s in a gas gun into thin aluminum perforation targets, subjecting the projectile to a complex multiaxial and time-dependent stress state that leads to catastrophic fracture. A soft-catch mechanism using low-density artificial snow was developed to recover the impact debris, and collected fragments were analyzed to determine their size distribution down to 30 μm. Though brittle fracture occurs along original particle boundaries, no power-law fragmentation behavior was observed as is seen in other low-toughness materials. An analytical theory is developed to predict the characteristic fragment size accounting for both the sharp onset of fragmentation and the effect of increasing impact velocity.

Scattering from extended targets in range-dependent fluctuating ocean-waveguides with clutter from theory and experiments.

Science.gov (United States)

Jagannathan, Srinivasan; Küsel, Elizabeth T; Ratilal, Purnima; Makris, Nicholas C

2012-08-01

Bistatic, long-range measurements of acoustic scattered returns from vertically extended, air-filled tubular targets were made during three distinct field experiments in fluctuating continental shelf waveguides. It is shown that Sonar Equation estimates of mean target-scattered intensity lead to large errors, differing by an order of magnitude from both the measurements and waveguide scattering theory. The use of the Ingenito scattering model is also shown to lead to significant errors in estimating mean target-scattered intensity in the field experiments because they were conducted in range-dependent ocean environments with large variations in sound speed structure over the depth of the targets, scenarios that violate basic assumptions of the Ingenito model. Green's theorem based full-field modeling that describes scattering from vertically extended tubular targets in range-dependent ocean waveguides by taking into account nonuniform sound speed structure over the target's depth extent is shown to accurately describe the statistics of the targets' scattered field in all three field experiments. Returns from the man-made targets are also shown to have a very different spectral dependence from the natural target-like clutter of the dominant fish schools observed, suggesting that judicious multi-frequency sensing may often provide a useful means of distinguishing fish from man-made targets.

The role of fragmentation mechanism in large-scale vapor explosions

International Nuclear Information System (INIS)

Liu, Jie

2003-01-01

A non-equilibrium, multi-phase, multi-component code PROVER-I is developed for propagation phase of vapor explosion. Two fragmentation models are used. The hydrodynamic fragmentation model is the same as Fletcher's one. A new thermal fragmentation model is proposed with three kinds of time scale for modeling instant fragmentation, spontaneous nucleation fragmentation and normal boiling fragmentation. The role of fragmentation mechanisms is investigated by the simulations of the pressure wave propagation and energy conversion ratio of ex-vessel vapor explosion. The spontaneous nucleation fragmentation results in a much higher pressure peak and a larger energy conversion ratio than hydrodynamic fragmentation. The instant fragmentation gives a slightly larger energy conversion ratio than spontaneous nucleation fragmentation, and the normal boiling fragmentation results in a smaller energy conversion ratio. The detailed analysis of the structure of pressure wave makes it clear that thermal detonation exists only under the thermal fragmentation circumstance. The high energy conversion ratio is obtained in a small vapor volume fraction. However, in larger vapor volume fraction conditions, the vapor explosion is weak. In a large-scale vapor explosion, the hydrodynamic fragmentation is essential when the pressure wave becomes strong, so a small energy conversion ratio is expected. (author)

Multi-target detection and positioning in crowds using multiple camera surveillance

Science.gov (United States)

Huang, Jiahu; Zhu, Qiuyu; Xing, Yufeng

2018-04-01

In this study, we propose a pixel correspondence algorithm for positioning in crowds based on constraints on the distance between lines of sight, grayscale differences, and height in a world coordinates system. First, a Gaussian mixture model is used to obtain the background and foreground from multi-camera videos. Second, the hair and skin regions are extracted as regions of interest. Finally, the correspondences between each pixel in the region of interest are found under multiple constraints and the targets are positioned by pixel clustering. The algorithm can provide appropriate redundancy information for each target, which decreases the risk of losing targets due to a large viewing angle and wide baseline. To address the correspondence problem for multiple pixels, we construct a pixel-based correspondence model based on a similar permutation matrix, which converts the correspondence problem into a linear programming problem where a similar permutation matrix is found by minimizing an objective function. The correct pixel correspondences can be obtained by determining the optimal solution of this linear programming problem and the three-dimensional position of the targets can also be obtained by pixel clustering. Finally, we verified the algorithm with multiple cameras in experiments, which showed that the algorithm has high accuracy and robustness.

Element Distribution and Multiplicity of Heavy Fragments

CERN Multimedia

2002-01-01

This experiment will measure the energy and angular distribution of heavy fragments produced in the reactions of |1|2C on several targets between |2|7Al and |2|3|8U at 86~MeV/u. The systematic investigation of a highly excited interaction region (fireball) by means of a clean N and Z identification of heavy tar fragments, may result in a better understanding of temperature concept and of the degree of equilibration of the local interaction region with respect to the total system. For this investigation a large-area position sensitive ionization chamber of 50~msr solid angle in conjunction with a time-of-flight telescope consisting of parallel-plate detectors will be used. \\\\ \\\\ In order to get information on the transverse momentum transfer and the inelasticity of the collision, the energy of the PROJECTILE-FRAGMENTS will be measured at forward angles with a plastic scintillator hodoscope. In addition to this inclusive measurement correlations between heavy fragments will be investigated by means of three pos...

Transverse velocity scaling in 197Au+197Au fragmentation

International Nuclear Information System (INIS)

Lukasik, J.; Hudan, S.; Lavaud, F.

2002-07-01

Invariant transverse-velocity spectra of intermediate-mass fragments were measured with the 4π multi-detector system INDRA for collisions of 197 Au on 197 Au at incident energies between 40 and 150 MeV per nucleon. Their scaling properties as a function of incident energy and atomic number Z are used to distinguish and characterize the emissions in (i) peripheral collisions at the projectile and target rapidities, and in (ii) central and (iii) peripheral collisions near mid-rapidity. The importance of dynamical effects is evident in all three cases and their origin is discussed. (orig.)

Effective source size, yield and beam profile from multi-layered bremsstrahlung targets

International Nuclear Information System (INIS)

Svensson, R.; Brahme, A.

1996-01-01

Modern conformal radiotherapy benefits from heterogeneous dose delivery using scanned narrow bremsstrahlung beams of high energy in combination with dynamic double focused multi-leaf collimation and purging magnets. When using a purging magnet to remove electrons and positrons the target space is limited and unorthodox thin multi-layered targets are needed. A computational technique has therefore been developed to determine the forward yield and the angular distributions of the bremsstrahlung beam as well as the size and location of the effective and the virtual photon point source for arbitrary multi-layer bremsstrahlung targets. The Gaussian approximation of the diffusion equation for the electrons has been used and convolved with the bremsstrahlung production process. For electrons with arbitrary emittance impinging on targets of any multi-layer and atomic number combination, the model is well applicable, at least for energies in the range 1-100 MeV. The intrinsic bremsstrahlung photon profile has been determined accurately by deconvolving the electron multiple scattering process from thin experimental beryllium target profiles. For electron pencil beams incident on a target of high density and atomic number such as tungsten, the size of the effective photon source stays at around a tenth of a millimetre. The effective photon source for low-Z materials such as Be, C and Al is located at depths from 3-7 mm in the target, decreasing with increasing atomic number. The effective photon source at off-axis positions then moves out considerably from the central axis, which should be considered when aligning collimators. For high-Z materials such as tungsten, the location of the effective photon source is at a few tenths of a millimetre deep. The virtual photon point source is located only a few tenths of a millimetre upstream of the effective photon source both for high- and low-Z materials. For 50 MeV electrons incident on multi-layered full range targets the radial

A multi-offset vertical profiling (VSP) experiment for anisotropy analysis and imaging

Energy Technology Data Exchange (ETDEWEB)

Grech, G. K.; Lawton, D. [Calgary Univ., AB (Canada)

2000-09-01

Vertical seismic profiling (VSP) and surface seismic data are used to image and locate hydrocarbon targets in the subsurface, hence the importance of assessing which formations exhibit seismic velocity anisotropy and quantify their parameters for use during seismic imaging. The purpose of the experiments described in this paper was to determine whether the multiple dipping thin shale beds overlying the target area in the Rocky Mountain Foothills in southern Alberta exhibit seismic velocity anisotropy and if so, how this phenomenon affects the image of the underlying target. Traveltime inversion of the first arrival data from the multi-offset VSP in the study area has revealed that the Cretaceous shales exhibit velocity anisotropy of about 10 degrees. For a target depth of 3000 m and moderate dips of 30 to 50 degrees in the anisotropic overburden, it would be reasonable to expect a lateral shift in the imaged location of the target of up to 300 m in the up-direction of overlying bedding. 8 refs., 9 figs.

Two-phase framework for optimal multi-target Lambert rendezvous

OpenAIRE

Bang, Jun; Ahn, Jaemyung

2017-01-01

This paper proposes a two-phase framework to solve an optimal multi-target Lambert rendezvous problem. The first phase solves a series of single-target rendezvous problems for all departure-arrival object pairs to generate the elementary solutions, which provides candidate rendezvous trajectories (elementary solutions). The second phase formulates a variant of traveling salesman problem (TSP) using the elementary solutions prepared in the first phase and determines the best rendezvous sequenc...

Fragment informatics and computational fragment-based drug design: an overview and update.

Science.gov (United States)

Sheng, Chunquan; Zhang, Wannian

2013-05-01

Fragment-based drug design (FBDD) is a promising approach for the discovery and optimization of lead compounds. Despite its successes, FBDD also faces some internal limitations and challenges. FBDD requires a high quality of target protein and good solubility of fragments. Biophysical techniques for fragment screening necessitate expensive detection equipment and the strategies for evolving fragment hits to leads remain to be improved. Regardless, FBDD is necessary for investigating larger chemical space and can be applied to challenging biological targets. In this scenario, cheminformatics and computational chemistry can be used as alternative approaches that can significantly improve the efficiency and success rate of lead discovery and optimization. Cheminformatics and computational tools assist FBDD in a very flexible manner. Computational FBDD can be used independently or in parallel with experimental FBDD for efficiently generating and optimizing leads. Computational FBDD can also be integrated into each step of experimental FBDD and help to play a synergistic role by maximizing its performance. This review will provide critical analysis of the complementarity between computational and experimental FBDD and highlight recent advances in new algorithms and successful examples of their applications. In particular, fragment-based cheminformatics tools, high-throughput fragment docking, and fragment-based de novo drug design will provide the focus of this review. We will also discuss the advantages and limitations of different methods and the trends in new developments that should inspire future research. © 2012 Wiley Periodicals, Inc.

Melt Fragmentation Characteristics of Metal Fuel with Melt Injection Mass during Initiating Phase of SFR Severe Accidents

Energy Technology Data Exchange (ETDEWEB)

Heo, Hyo; Lee, Min Ho; Bang, In Cheol [Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of); Jerng, Dong Wook [Chung-Ang Univ., Seoul (Korea, Republic of)

2016-05-15

The PGSFR has adopted the metal fuel for its inherent safety under severe accident conditions. However, this fuel type is not demonstrated clearly yet under the such severe accident conditions. Additional experiments for examining these issues should be performed to support its licensing activities. Under initiating phase of hypothetic core disruptive accident (HCDA) conditions, the molten metal could be better dispersed and fragmented into the coolant channel than in the case of using oxide fuel. This safety strategy provides negative reactivity driven by a good dispersion of melt. If the coolant channel does not sufficient coolability, the severe recriticality would occur within the core region. Thus, it is important to examine the extent of melt fragmentation. The fragmentation behaviors of melt are closely related to a formation of debris shape. Once the debris shape is formed through the fragmentation process, its coolability is determined by the porosity or thermal conductivity of the melt. There were very limited studies for transient irradiation experiments of the metal fuel. These studies were performed by Transient Reactor Test Facility (TREAT) M series tests in U.S. The TREAT M series tests provided basic information of metal fuel performance under transient conditions. The effect of melt injection mass was evaluated in terms of the fragmentation behaviors of melt. These behaviors seemed to be similar between single-pin and multi-pins failure condition. However, the more melt was agglomerated in case of multi-pins failure.

A rotating target wheel system for gammasphere

International Nuclear Information System (INIS)

Greene, J. P.

1999-01-01

A description is given for a low-mass, rotating target wheel to be used within the Gammasphere target chamber. This system was developed for experiments employing high beam currents in order to extend lifetimes of targets using low-melting point target material. The design is based on a previously successful implementation of rotating target wheels for the Argonne Positron Experiment (APEX) as well as the Fragment Mass Analyser (FMA) at ATLAS (Argonne Tandem Linac Accelerator System). A brief history of these rotating target wheel systems is given as well as a discussion on target preparation and performance

Cooperative multi-robot observation of multiple moving targets

International Nuclear Information System (INIS)

Parker, L.E.; Emmons, B.A.

1997-01-01

An important issue that arises in the automation of many security, surveillance, and reconnaissance tasks is that of monitoring, or observing, the movements of targets navigating in a bounded area of interest. A key research issue in these problems is that of sensor placement--determining where sensors should be located to maintain the targets in view. In complex applications of this type, the use of multiple sensors dynamically moving over time is required. In this paper, the authors investigate the sue of a cooperative team of autonomous sensor-based robots for multi-robot observation of multiple moving targets. They focus primarily on developing the distributed control strategies that allow the robot team to attempt to maximize the collective tie during which each object is being observed by at least one robot in the area of interest. The initial efforts in this problem address the aspects of distributed control in homogeneous robot teams with equivalent sensing and movement capabilities working in an uncluttered, bounded area. This paper first formalizes the problem, discusses related work, and then shows that this problem is NP-hard. They then present a distributed approximate approach to solving this problem that combines low-level multi-robot control with higher-level control

Universality of projectile fragmentation model

International Nuclear Information System (INIS)

Chaudhuri, G.; Mallik, S.; Das Gupta, S.

2012-01-01

Presently projectile fragmentation reaction is an important area of research as it is used for the production of radioactive ion beams. In this work, the recently developed projectile fragmentation model with an universal temperature profile is used for studying the charge distributions of different projectile fragmentation reactions with different projectile target combinations at different incident energies. The model for projectile fragmentation consists of three stages: (i) abrasion, (ii) multifragmentation and (iii) evaporation

Low-communication parallel quantum multi-target preimage search

NARCIS (Netherlands)

Banegas, G.S.; Bernstein, D.J.; Adams, Carlisle; Camenisch, Jan

2017-01-01

The most important pre-quantum threat to AES-128 is the 1994 van Oorschot–Wiener “parallel rho method”, a low-communication parallel pre-quantum multi-target preimage-search algorithm. This algorithm uses a mesh of p small processors, each running for approximately 2 128 /pt 2128/pt fast steps, to

Universal odd-even staggering in isotopic fragmentation and spallation cross sections of neutron-rich fragments

Science.gov (United States)

Mei, B.; Tu, X. L.; Wang, M.

2018-04-01

An evident odd-even staggering (OES) in fragment cross sections has been experimentally observed in many fragmentation and spallation reactions. However, quantitative comparisons of this OES effect in different reaction systems are still scarce for neutron-rich nuclei near the neutron drip line. By employing a third-order difference formula, the magnitudes of this OES in extensive experimental cross sections are systematically investigated for many neutron-rich nuclei with (N -Z ) from 1 to 23 over a broad range of atomic numbers (Z ≈3 -50 ). A comparison of these magnitude values extracted from fragment cross sections measured in different fragmentation and spallation reactions with a large variety of projectile-target combinations over a wide energy range reveals that the OES magnitude is almost independent of the projectile-target combinations and the projectile energy. The weighted average of these OES magnitudes derived from cross sections accurately measured in different reaction systems is adopted as the evaluation value of the OES magnitude. These evaluated OES magnitudes are recommended to be used in fragmentation and spallation models to improve their predictions for fragment cross sections.

Isotopic resolution of fission fragments from 238U + 12C transfer and fusion reactions

International Nuclear Information System (INIS)

Caamano, M.; Rejmund, F.; Derkx, X.; Schmidt, K. H.; Andouin, L.; Bacri, C. O.; Barreau, G.; Benlliure, J.; Casarejos, E.; Fernandez-Dominguez, B.; Gaudefroy, L.; Golabek, C.; Jurado, B.; Lemasson, A.; Navin, A.; Rejmund, M.; Roger, T.; Shrivastava, A.; Schmitt, C.; Taieb, J.

2010-01-01

Recent results from an experiment at GANIL, performed to investigate the main properties of fission-fragment yields and energy distributions in different fissioning nuclei as a function of the excitation energy, in a neutron-rich region of actinides, are presented. Transfer reactions in inverse kinematics between a 238 U beam and a 12 C target produced different actinides, within a range of excitation energy below 30 MeV. These fissioning nuclei are identified by detecting the target-like recoil, and their kinetic and excitation energy are determined from the reconstruction of the transfer reaction. The large-acceptance spectrometer VAMOS was used to identify the mass, atomic number and charge state of the fission fragments in flight. As a result, the characteristics of the fission-fragment isotopic distributions of a variety of neutron-rich actinides are observed for the first time over the complete range of fission fragments. (authors)

Heavy quarks fragmentation in charmed mesons in DELPHI experiment at LEP; Etude de la fragmentation des quarks lourds en mesons charmes dans l`experience Delphi au LEP

Energy Technology Data Exchange (ETDEWEB)

Levy, J.M.

1994-04-01

With the big statistics expected at LEP, the electroweak sector of the Standard Model can be tested as well as the theory of strong interactions. Quantum Chromo-Dynamics is indeed predictive for quarks properties, but does not explain how quarks fragment into hadrons. So far the hadronization can only be described with phenomenological models. The work presented in this thesis was performed on the DELPHI experiment at LEP and concerns the production and the fragmentation of heavy quarks into charmed mesons D , D* and D**. With the whole statistics of 1991 and 1992 (1 013 300 hadronic decays of the Z), more than 4500 charmed mesons decays have been reconstructed in the channels D{sup 0}{yields} K{sup -} {pi}{sup +} , D{sup +}{yields} K{sup -} {pi}{sup +}{pi}+ and D{sup *}+{yields} D{sup 0}{pi}{sup +} followed by D{sup 0}{yields} K{sup -}{pi}{sup +} . Using also 1993 data and the channel D{sup 0}{yields} K{sup -}{pi}{sup +}{pi}{sup +}{pi}{sup -} , evidence for D** production is presented. For the first time, the production rate is measured for each D meson separately for cc and bb contributions. In fact, D mesons can be produced either directly from the fragmentation of c quark or un-directly from the fragmentation of b quark into B mesons which decay into D mesons. (authors). 120 refs.

Global calibration of multi-cameras with non-overlapping fields of view based on photogrammetry and reconfigurable target

Science.gov (United States)

Xia, Renbo; Hu, Maobang; Zhao, Jibin; Chen, Songlin; Chen, Yueling

2018-06-01

Multi-camera vision systems are often needed to achieve large-scale and high-precision measurement because these systems have larger fields of view (FOV) than a single camera. Multiple cameras may have no or narrow overlapping FOVs in many applications, which pose a huge challenge to global calibration. This paper presents a global calibration method for multi-cameras without overlapping FOVs based on photogrammetry technology and a reconfigurable target. Firstly, two planar targets are fixed together and made into a long target according to the distance between the two cameras to be calibrated. The relative positions of the two planar targets can be obtained by photogrammetric methods and used as invariant constraints in global calibration. Then, the reprojection errors of target feature points in the two cameras’ coordinate systems are calculated at the same time and optimized by the Levenberg–Marquardt algorithm to find the optimal solution of the transformation matrix between the two cameras. Finally, all the camera coordinate systems are converted to the reference coordinate system in order to achieve global calibration. Experiments show that the proposed method has the advantages of high accuracy (the RMS error is 0.04 mm) and low cost and is especially suitable for on-site calibration.

Normalization for triple-target microarray experiments

Directory of Open Access Journals (Sweden)

Magniette Frederic

2008-04-01

Full Text Available Abstract Background Most microarray studies are made using labelling with one or two dyes which allows the hybridization of one or two samples on the same slide. In such experiments, the most frequently used dyes are Cy3 and Cy5. Recent improvements in the technology (dye-labelling, scanner and, image analysis allow hybridization up to four samples simultaneously. The two additional dyes are Alexa488 and Alexa494. The triple-target or four-target technology is very promising, since it allows more flexibility in the design of experiments, an increase in the statistical power when comparing gene expressions induced by different conditions and a scaled down number of slides. However, there have been few methods proposed for statistical analysis of such data. Moreover the lowess correction of the global dye effect is available for only two-color experiments, and even if its application can be derived, it does not allow simultaneous correction of the raw data. Results We propose a two-step normalization procedure for triple-target experiments. First the dye bleeding is evaluated and corrected if necessary. Then the signal in each channel is normalized using a generalized lowess procedure to correct a global dye bias. The normalization procedure is validated using triple-self experiments and by comparing the results of triple-target and two-color experiments. Although the focus is on triple-target microarrays, the proposed method can be used to normalize p differently labelled targets co-hybridized on a same array, for any value of p greater than 2. Conclusion The proposed normalization procedure is effective: the technical biases are reduced, the number of false positives is under control in the analysis of differentially expressed genes, and the triple-target experiments are more powerful than the corresponding two-color experiments. There is room for improving the microarray experiments by simultaneously hybridizing more than two samples.

Production of nuclear fragments from the interactions of 24 GeV/c protons in a gold target

CERN Document Server

Herz, A J; O'Sullivan, D; Thompson, A

1976-01-01

Lexan polycarbonate track detectors have been used to determine the charge and energy spectra of nuclear fragments with Z>or=6 and with kinetic energies as low as approximately=1.0 MeV/nucleon emitted from a thin gold target bombarded with 24 GeV/c protons. (8 refs).

EURISOL-DS MULTI-MW TARGET ISSUES: BEAM WINDOW AND TRANSVERSE FILM TARGET

CERN Document Server

Adonai Herrera-Martínez, Yacine Kadi

The analysis of the EURISOL-DS Multi_MW target precise geometry (Fig.1) has proved that large fission yields can be achieved with a 4 MW, providing a technically feasible design to evacuate the power deposited in the liquid mercury. Different designs for the mercury flow have been proposed, which maintain its temperature below the boiling point with moderate flow speeds (maximum 4 m/s).

Multi-Target Tracking via Mixed Integer Optimization

Science.gov (United States)

2016-05-13

an easily interpretable global objective function. Furthermore, we propose a greedy heuristic which quickly finds good solutions. We extend both the... heuristic and the MIO model to scenarios with missed detections and false alarms. Index Terms—optimization; multi-target tracking; data asso- ciation...energy in [14] and then again as a minimization of discrete-continuous energy in [15]. These algorithms aim to more accurately represent the nature of the

Targeting lysine specific demethylase 4A (KDM4A) tandem TUDOR domain - A fragment based approach.

Science.gov (United States)

Upadhyay, Anup K; Judge, Russell A; Li, Leiming; Pithawalla, Ron; Simanis, Justin; Bodelle, Pierre M; Marin, Violeta L; Henry, Rodger F; Petros, Andrew M; Sun, Chaohong

2018-06-01

The tandem TUDOR domains present in the non-catalytic C-terminal half of the KDM4A, 4B and 4C enzymes play important roles in regulating their chromatin localizations and substrate specificities. They achieve this regulatory role by binding to different tri-methylated lysine residues on histone H3 (H3-K4me3, H3-K23me3) and histone H4 (H4-K20me3) depending upon the specific chromatin environment. In this work, we have used a 2D-NMR based fragment screening approach to identify a novel fragment (1a), which binds to the KDM4A-TUDOR domain and shows modest competition with H3-K4me3 binding in biochemical as well as in vitro cell based assays. A co-crystal structure of KDM4A TUDOR domain in complex with 1a shows that the fragment binds stereo-specifically to the methyl lysine binding pocket forming a network of strong hydrogen bonds and hydrophobic interactions. We anticipate that the fragment 1a can be further developed into a novel allosteric inhibitor of the KDM4 family of enzymes through targeting their C-terminal tandem TUDOR domain. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anomalous nuclear fragments

International Nuclear Information System (INIS)

Karmanov, V.A.

1983-01-01

Experimental data are given, the status of anomalon problem is discussed, theoretical approaches to this problem are outlined. Anomalons are exotic objects formed following fragmentation of nuclei-targets under the effect of nuclei - a beam at the energy of several GeV/nucleon. These nuclear fragments have an anomalously large cross section of interaction and respectively, small free path, considerably shorter than primary nuclei have. The experimental daa are obtained in accelerators following irradiation of nuclear emulsions by 16 O, 56 Fe, 40 Ar beams, as well as propane by 12 C beams. The experimental data testify to dependence of fragment free path on the distance L from the point of the fragment formation. A decrease in the fragment free path is established more reliably than its dependence on L. The problem of the anomalon existence cannot be yet considered resolved. Theoretical models suggested for explanation of anomalously large cross sections of nuclear fragment interaction are variable and rather speculative

Neutron emission from projectile-like and target-like fragments in the 18O+48Ti reaction at E(18O)=116 MeV

International Nuclear Information System (INIS)

Chambon, B.; Drain, D.; Pastor, C.; Dauchy, A.; Giorni, A.; Morand, C.

1982-07-01

Angular correlations between neutrons and projectile-like fragments detected near the grazing angle were analysed by assuming two incoherent neutrons sources. One source describes slower neutrons evaporated by target-like fragments in equilibrium. The faster, forward-peaked neutrons originate from a second source strongly correlated with the projectile-like fragments with regards to velocity and direction. In some cases neutron emission may even be attributed to known neutron emitter levels in excited ejectiles

A new hybrid target concept for multi-keV X-ray sources

International Nuclear Information System (INIS)

Primout, M.; Babonneau, D.; Jacquet, L.; Villette, B.; Girard, F.; Brebion, D.; Stemmler, P.; Fournier, K.B.; Marrs, R.; May, M.J.; Heeter, R.F.; Wallace, R.J.; Nishimura, H.; Fujioka, S.; Tanabe, M.; Nagai, H.

2013-01-01

A novel concept for using hybrid targets to create multi-keV X-ray sources was tested on the GEKKO XII facility of the Osaka University and on the OMEGA facility of the University of Rochester. The sources were made via laser irradiation of a titanium foil placed at the end of a plastic cylinder, filled with a very low-density (2 and 5 mg/cm 3 ) silicon-dioxide aerogel that was designed to control the longitudinal expansion of the titanium plasma. Preliminary calculations were used to determine optimal conditions for the aerogel density, cylinder diameter and length that maximize multi-keV X-ray emission. The X-ray emission power was measured on OMEGA using absolutely calibrated broad-band, diode-based CEA diagnostics, in addition to high resolution crystal spectrometers. On GEKKO XII, the heat wave propagation velocity in the aerogel was also measured with an X-ray framing camera. The advantage of using the thermal wave generated in the aerogel to heat a solid material to increase the conversion efficiency has not been fully demonstrated in these experiments. However, it was shown that a 5 mg/cm 3 aerogel placed in front of a titanium foil can improve the x-ray conversion efficiency with respect to the case of 2 mg/cm 3 for some target diameter and length. (authors)

Proton induced target fragmentation studies on solid state nuclear track detectors using Carbon radiators

Science.gov (United States)

Szabó, J.; Pálfalvi, J. K.; Strádi, A.; Bilski, P.; Swakoń, J.; Stolarczyk, L.

2018-04-01

One of the limiting factors of an astronaut's career is the dose received from space radiation. High energy protons, being the main components of the complex radiation field present on a spacecraft, give a significant contribution to the dose. To investigate the behavior of solid state nuclear track detectors (SSNTDs) if they are irradiated by such particles, SSNTD stacks containing carbon blocks were exposed to high energy proton beams (70, 100, 150 and 230 MeV) at the Proteus cyclotron, IFJ PAN -Krakow. The incident protons cannot be detected directly; however, tracks of secondary particles, recoils and fragments of the constituent atoms of the detector material and of the carbon radiator are formed. It was found that as the proton energy increases, the number of tracks induced in the PADC material by secondary particles decreases. From the measured geometrical parameters of the tracks the linear energy transfer (LET) spectrum and the dosimetric quantities were determined, applying appropriate calibration. In the LET spectra the LET range of the most important secondary particles could be identified and their abundance showed differences in the spectra if the detectors were short or long etched. The LET spectra obtained on the SSNTDs irradiated by protons were compared to LET spectra of detectors flown on the International Space Station (ISS): they were quite similar, resulting in a quality factor difference of only 5%. Thermoluminescent detectors (TLDs) were applied in each case to measure the dose from primary protons and other lower LET particles present in space. Comparing and analyzing the results of the TLD and SSNTD measurements, it was obtained that proton induced target fragments contributed to the total absorbed dose in 3.2% and to the dose equivalent in 14.2% in this particular space experiment.

Identification and characterization of carprofen as a multi-target FAAH/COX inhibitor

Science.gov (United States)

Favia, Angelo D.; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

2013-01-01

Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the non-steroid anti-inflammatory drug, carprofen, as a multi-target-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2 and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several racemic derivatives of carprofen, sharing this multi-target activity. This may result in improved analgesic efficacy and reduced side effects (Naidu, et al (2009) J Pharmacol Exp Ther 329, 48-56; Fowler, C.J. et al. (2012) J Enzym Inhib Med Chem Jan 6; Sasso, et al (2012) Pharmacol Res 65, 553). The new compounds are among the most potent multi-target FAAH/COXs inhibitors reported so far in the literature, and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs. PMID:23043222

Coulomb effects in low-energy nuclear fragmentation

Science.gov (United States)

Wilson, John W.; Chun, Sang Y.; Badavi, Francis F.; John, Sarah

1993-01-01

Early versions of the Langley nuclear fragmentation code NUCFRAG (and a publicly released version called HZEFRG1) assumed straight-line trajectories throughout the interaction. As a consequence, NUCFRAG and HZEFRG1 give unrealistic cross sections for large mass removal from the projectile and target at low energies. A correction for the distortion of the trajectory by the nuclear Coulomb fields is used to derive fragmentation cross sections. A simple energy-loss term is applied to estimate the energy downshifts that greatly alter the Coulomb trajectory at low energy. The results, which are far more realistic than prior versions of the code, should provide the data base for future transport calculations. The systematic behavior of charge-removal cross sections compares favorably with results from low-energy experiments.

Laboratory experiments on fragmentation of highly-viscous bubbly syrup

Science.gov (United States)

Kurihara, H.; Kameda, M.; Ichihara, M.

2006-12-01

Fragmentation of vesicular magma by rapid decompression is a key process in explosive eruptions. To determine the fragmentation criteria, we carried out laboratory experiments on magma fragmentation using analogous materials. We used commercial syrup as an analogous material of magma, because the viscosity was widely altered by adding or subtracting water contents in the syrup. We made the bubbly syrup by adding hydrogen peroxide with manganese oxide in the syrup. The amount of hydrogen peroxide is proportional to the gas volume fraction in the syrup. We measured the rheological properties of the syrup. Zero shear viscosity η was measured by a rotating viscometer and a fiber elongation technique. Glass transition temperature was measured by differential scanning calorimetry. The measured data indicated that the temperature dependence of viscosity was described well using Williams-Landel-Ferry (WLF) equation. The solid content of syrup alters the viscosity as well as the glass transition temperature, though it may hardly affect the rigidity μ, which was measured by ultrasonic test in our previous work. We used a pressurized vertical tube with a large vacuum vessel to apply the rapid decompression on the material. An acrylic container, filled with the bubbly syrup, was placed in the bottom of the pressurized tube. By rupturing the diaphragms inserted between the tube and the vacuum vessel, the bubbly syrup is rapidly decompressed due to expansion of the pressurized gas in the tube. A high-speed video camera was used to obtain sequential images of the materials. Pressure transducers were mounted on the sidewall of the tube and the bottom of the container. The initial pressure was varied from 1 MPa to 5 MPa. The gas-volume fraction of the syrup under pressure was fixed as 2 % to 20%. The viscosity varied from 105 Pa·s to 108 Pa·s. We successfully observed three principal behaviors using the present analogous material; brittle fragmentation, partial fracture and

Selection and Characterization of Single Chain Antibody Fragments Specific for Hsp90 as a Potential Cancer Targeting Molecule

Directory of Open Access Journals (Sweden)

Edyta Petters

2015-08-01

Full Text Available Heat shock proteins play an essential role in facilitating malignant transformation and they have been recognized as important factors in human cancers. One of the key elements of the molecular chaperones machinery is Hsp90 and it has recently become a target for anticancer therapeutic approaches. The potential and importance of Hsp90-directed agents becomes apparent when one realizes that disruption of Hsp90 function may influence over 200 oncogenic client proteins. Here, we described the selection and characterization of Hsp90-specific antibody fragments from commercially available Tomlinson I and J phage display libraries. The affinities of Hsp90-binding scFv variants were measured using SPR method. Then, based on the best clone selected, we performed the affinity maturation procedure and obtained valuable Hsp90-specific clones. The selected binders were expressed and applied for immunostaining, ELISA and SPR analysis using model cancer cell lines. All performed experiments confirmed the ability of selected antibodies to interact with the Hsp90. Therefore, the presented Hsp90-specific scFv, might be a starting point for the development of a novel antibody-based strategy targeting cancer.

A fragment separator at LBL for beta-NMR experiment

International Nuclear Information System (INIS)

Matsuta, K.; Ozawa, A.; Nojiri, Y.; Minamisono, T.; Fukuda, M.; Kitagawa, A.; Ohtsubo, T.; Momota, S.; Fukuda, S.; Matsuo, Y.; Takechi, H.; Minami, I.; Sugimoto, K.; Tanihata, I.; Omata, K.; Alonso, J.R.; Krebs, G.F.; Symons, T.J.M.

1992-03-01

The Beam 44 fragment separator was built at the Bevalac of LBL for NMR studies of beta emitting nuclei. 37 K, 39 Ca, and 43 Ti fragments originating from 40 Ca and 46 Ti primary beams were separated by the separator for NMR studies on these nuclei. Nuclear spin polarization was created in 39 Ca and 43 Ti using the tilted foil technique (TFT), and the magnetic moment of 43 Ti was deduced. Fragment polarization was measured for 37 K and 39 Ca emitted to finite deflection angles. The Beam 44 fragment separator in combination with a proper polarization technique, such as TFT or fragment polarization, has been very effective for such NMR studies

Intermittent behavior of fast and slow target fragments from 16O-AgBr interactions at 3.7 A GeV

International Nuclear Information System (INIS)

Li Junsheng; Zhang Donghai; Liu Fuhu

2008-01-01

Angular distributions of fast and slow target particles produced in 16 O-AgBr interaction at 3.7 A GeV have been reported. Intermittency and fractal behavior have been studied for emission spectra of target associated fast and slow particles. Intermittent behavior is observed for both knocked out and slow target fragments. In both the cases anomalous dimensions are seen to increase with the order of moments thereby indicating the association of multifractility with production mechanism of both fast and slow target associated particles

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry.

Science.gov (United States)

Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K H

2016-08-01

Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240-fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Gas-phase fragmentation of peptides to increase the spatial resolution of the Hydrogen Exchange Mass Spectrometry experiment

DEFF Research Database (Denmark)

Jensen, Pernille Foged; Rand, Kasper Dyrberg

2016-01-01

are produced after precursor ion selection and thus do not add complexity to the LC-MS analysis. The key to obtaining optimal spatial resolution in a hydrogen exchange mass spectrometry (HX-MS) experiment is the fragmentation efficiency. This chapter discusses common fragmentation techniques like collision....../D scrambling, thus making them suitable for HX applications. By combining the classic bottom-up HX-MS workflow with gas-phase fragmentation by ETD, detailed information on protein HX can be obtained....

A Gateway MultiSite recombination cloning toolkit.

Directory of Open Access Journals (Sweden)

Lena K Petersen

Full Text Available The generation of DNA constructs is often a rate-limiting step in conducting biological experiments. Recombination cloning of single DNA fragments using the Gateway system provided an advance over traditional restriction enzyme cloning due to increases in efficiency and reliability. Here we introduce a series of entry clones and a destination vector for use in two, three, and four fragment Gateway MultiSite recombination cloning whose advantages include increased flexibility and versatility. In contrast to Gateway single-fragment cloning approaches where variations are typically incorporated into model system-specific destination vectors, our Gateway MultiSite cloning strategy incorporates variations in easily generated entry clones that are model system-independent. In particular, we present entry clones containing insertions of GAL4, QF, UAS, QUAS, eGFP, and mCherry, among others, and demonstrate their in vivo functionality in Drosophila by using them to generate expression clones including GAL4 and QF drivers for various trp ion channel family members, UAS and QUAS excitatory and inhibitory light-gated ion channels, and QUAS red and green fluorescent synaptic vesicle markers. We thus establish a starter toolkit of modular Gateway MultiSite entry clones potentially adaptable to any model system. An inventory of entry clones and destination vectors for Gateway MultiSite cloning has also been established (www.gatewaymultisite.org.

Developments in SPR Fragment Screening.

Science.gov (United States)

Chavanieu, Alain; Pugnière, Martine

2016-01-01

Fragment-based approaches have played an increasing role alongside high-throughput screening in drug discovery for 15 years. The label-free biosensor technology based on surface plasmon resonance (SPR) is now sensitive and informative enough to serve during primary screens and validation steps. In this review, the authors discuss the role of SPR in fragment screening. After a brief description of the underlying principles of the technique and main device developments, they evaluate the advantages and adaptations of SPR for fragment-based drug discovery. SPR can also be applied to challenging targets such as membrane receptors and enzymes. The high-level of immobilization of the protein target and its stability are key points for a relevant screening that can be optimized using oriented immobilized proteins and regenerable sensors. Furthermore, to decrease the rate of false negatives, a selectivity test may be performed in parallel on the main target bearing the binding site mutated or blocked with a low-off-rate ligand. Fragment-based drug design, integrated in a rational workflow led by SPR, will thus have a predominant role for the next wave of drug discovery which could be greatly enhanced by new improvements in SPR devices.

Penetration of a Small Caliber Projectile into Single and Multi-layered Targets

Directory of Open Access Journals (Sweden)

Riad A.M.

2010-06-01

Full Text Available The normal penetration of armor-piercing projectiles into single and multi-layered steel plates has been investigated. An experimental program has been conducted to study the effect of spaced and in-contact layered targets on their ballistic resistance. Armor piercing projectiles with caliber of 7.62 mm were fired against a series of single and multi-layered steel targets. The projectile impact velocities were ranged from 300-600 m/s, whereas the total thicknesses of the tested single, spaced and in-contact layered steel targets were 3 mm. The penetration process of different tested target configurations has been simulated using Autodayn-2D hydrocode. The experimental measurements of the present work were used to discuss the effect of impact velocity, target configurations and number of layers of different spaced and in-contact layered steel targets on their ballistic resistance. In addition, the post-firing examination of the tested targets over the used impact velocity range showed that the single and each layer of spaced and in-contact laminated steel targets were failed by petalling. Finally, the obtained experimental measurements were compared with the corresponding numerical results of Autodyn-2D hydrocode, good agreement was generally obtained.

Targets for the APEX experiment at ATLAS

International Nuclear Information System (INIS)

Greene, J.P.; Thomas, G.E.; Leonard, R.H.

1994-01-01

Targets of lead, tantalum, thorium and uranium have been produced for experiments with the APEX (Argonne Positron Experiment) apparatus at ATLAS (Argonne Tandem Linac Accelerator System). APEX is a device built at Argonne National Laboratory to investigate the anomalous positrons observed in collisions of very heavy ion beams on heavy targets. Both fixed and rotating targets have been used. The rotating target system involves a 4-quadrant wheel rotating at speeds up to 700 rpm with the position encoded into the data stream. In addition to the hundreds of targets produced for the heavy-ion reactions studied, a wide variety of targets were employed for beam diagnostics, detector calibration and target wheel development. The experiment used very heavy ion beams ( 238 U, 206 Pb and 208 Pb) from ATLAS and targets of 206 Pb, 208 Pb, 232 Th and 238 U produced in the laboratory

UPA-sensitive ACPP-conjugated nanoparticles for multi-targeting therapy of brain glioma.

Science.gov (United States)

Zhang, Bo; Zhang, Yujie; Liao, Ziwei; Jiang, Ting; Zhao, Jingjing; Tuo, Yanyan; She, Xiaojian; Shen, Shun; Chen, Jun; Zhang, Qizhi; Jiang, Xinguo; Hu, Yu; Pang, Zhiqing

2015-01-01

Now it is well evidenced that tumor growth is a comprehensive result of multiple pathways, and glioma parenchyma cells and stroma cells are closely associated and mutually compensatory. Therefore, drug delivery strategies targeting both of them simultaneously might obtain more promising therapeutic benefits. In the present study, we developed a multi-targeting drug delivery system modified with uPA-activated cell-penetrating peptide (ACPP) for the treatment of brain glioma (ANP). In vitro experiments demonstrated nanoparticles (NP) decorated with cell-penetrating peptide (CPP) or ACPP could significantly improve nanoparticles uptake by C6 glioma cells and nanoparticles penetration into glioma spheroids as compared with traditional NP and thus enhanced the therapeutic effects of its payload when paclitaxel (PTX) was loaded. In vivo imaging experiment revealed that ANP accumulated more specifically in brain glioma site than NP decorated with or without CPP. Brain slides further showed that ACPP contributed to more nanoparticles accumulation in glioma site, and ANP could co-localize not only with glioma parenchyma cells, but also with stroma cells including neo-vascular cells and tumor associated macrophages. The pharmacodynamics results demonstrated ACPP could significantly improve the therapeutic benefits of nanoparticles by significantly prolonging the survival time of glioma bearing mice. In conclusion, the results suggested that nanoparticles modified with uPA-sensitive ACPP could reach multiple types of cells in glioma tissues and provide a novel strategy for glioma targeted therapy.

Fission fragment yields from heavy-ion-induced reactions measured with a fragment separator

Science.gov (United States)

Tarasov, O. B.; Delaune, O.; Farget, F.; Morrissey, D. J.; Amthor, A. M.; Bastin, B.; Bazin, D.; Blank, B.; Cacéres, L.; Chbihi, A.; Fernández-Dominguez, B.; Grévy, S.; Kamalou, O.; Lukyanov, S. M.; Mittig, W.; Pereira, J.; Perrot, L.; Saint-Laurent, M.-G.; Savajols, H.; Sherrill, B. M.; Stodel, C.; Thomas, J. C.; Villari, A. C.

2018-04-01

The systematic study of fission fragment yields under different initial conditions has provided valuable experimental data for benchmarking models of fission product yields. Nuclear reactions using inverse kinematics coupled to the use of a high-resolution spectrometer with good fragment identification are shown here to be a powerful tool to measure the inclusive isotopic yields of fission fragments. In-flight fusion-fission was used in this work to produce secondary beams of neutron-rich isotopes in the collisions of a 238U beam at 24 MeV/u with 9Be and 12C targets at GANIL using the LISE3 fragment separator. Unique identification of the A, Z, and atomic charge state, q, of fission products was attained with the Δ E- TKE-B ρ- ToF measurement technique. Mass, and atomic number distributions are reported for the two reactions. The results show the importance of different reaction mechanisms in the two cases. The optimal target material for higher yields of neutron-rich high- Z isotopes produced in fusion-fission reactions as a function of projectile energy is discussed.

A comparison of synthetic oligodeoxynucleotides, DNA fragments and AAV-1 for targeted episomal and chromosomal gene repair

Directory of Open Access Journals (Sweden)

Leclerc Xavier

2009-04-01

Full Text Available Abstract Background Current strategies for gene therapy of inherited diseases consist in adding functional copies of the gene that is defective. An attractive alternative to these approaches would be to correct the endogenous mutated gene in the affected individual. This study presents a quantitative comparison of the repair efficiency using different forms of donor nucleic acids, including synthetic DNA oligonucleotides, double stranded DNA fragments with sizes ranging from 200 to 2200 bp and sequences carried by a recombinant adeno-associated virus (rAAV-1. Evaluation of each gene repair strategy was carried out using two different reporter systems, a mutated eGFP gene or a dual construct with a functional eGFP and an inactive luciferase gene, in several different cell systems. Gene targeting events were scored either following transient co-transfection of reporter plasmids and donor DNAs, or in a system where a reporter construct was stably integrated into the chromosome. Results In both episomal and chromosomal assays, DNA fragments were more efficient at gene repair than oligonucleotides or rAAV-1. Furthermore, the gene targeting frequency could be significantly increased by using DNA repair stimulating drugs such as doxorubicin and phleomycin. Conclusion Our results show that it is possible to obtain repair frequencies of 1% of the transfected cell population under optimized transfection protocols when cells were pretreated with phleomycin using rAAV-1 and dsDNA fragments.

Molecular investigations of protriptyline as a multi-target directed ligand in Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Sneha B Bansode

Full Text Available Alzheimer's disease (AD is a complex neurodegenerative disorder involving multiple cellular and molecular processes. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies. The repositioning of existing non-toxic drugs could dramatically reduce the time and costs involved in developmental and clinical trial stages. In this study, preliminary screening of 140 FDA approved nervous system drugs by docking suggested the viability of the tricyclic group of antidepressants against three major AD targets, viz. Acetylcholinesterase (AChE, β-secretase (BACE-1, and amyloid β (Aβ aggregation, with one member, protriptyline, showing highest inhibitory activity. Detailed biophysical assays, together with isothermal calorimetry, fluorescence quenching experiments, kinetic studies and atomic force microscopy established the strong inhibitory activity of protriptyline against all three major targets. The molecular basis of inhibition was supported with comprehensive molecular dynamics simulations. Further, the drug inhibited glycation induced amyloid aggregation, another important causal factor in AD progression. This study has led to the discovery of protriptyline as a potent multi target directed ligand and established its viability as a promising candidate for AD treatment.

Assessment of berberine as a multi-target antimicrobial: a multi-omics study for drug discovery and repositioning.

Science.gov (United States)

Karaosmanoglu, Kubra; Sayar, Nihat Alpagu; Kurnaz, Isil Aksan; Akbulut, Berna Sariyar

2014-01-01

Postgenomics drug development is undergoing major transformation in the age of multi-omics studies and drug repositioning. Rather than applications solely in personalized medicine, omics science thus additionally offers a better understanding of a broader range of drug targets and drug repositioning. Berberine is an isoquinoline alkaloid found in many medicinal plants. We report here a whole genome microarray study in tandem with proteomics techniques for mining the plethora of targets that are putatively involved in the antimicrobial activity of berberine against Escherichia coli. We found DNA replication/repair and transcription to be triggered by berberine, indicating that nucleic acids, in general, are among its targets. Our combined transcriptomics and proteomics multi-omics findings underscore that, in the presence of berberine, cell wall or cell membrane transport and motility-related functions are also specifically regulated. We further report a general decline in metabolism, as seen by repression of genes in carbohydrate and amino acid metabolism, energy production, and conversion. An involvement of multidrug efflux pumps, as well as reduced membrane permeability for developing resistance against berberine in E. coli was noted. Collectively, these findings offer original and significant leads for omics-guided drug discovery and future repositioning approaches in the postgenomics era, using berberine as a multi-omics case study.

Dual Fragment Impact of PBX Charges

Science.gov (United States)

Haskins, Peter; Briggs, Richard; Leeming, David; White, Nathan; Cheese, Philip; DE&S MoD UK Team; Ordnance Test Solutions Ltd Team

2017-06-01

Fragment impact can pose a significant hazard to many systems containing explosives or propellants. Testing for this threat is most commonly carried out using a single fragment. However, it can be argued that an initial fragment strike (or strikes) could sensitise the energetic material to subsequent impacts, which may then lead to a more violent reaction than would have been predicted based upon single fragment studies. To explore this potential hazard we have developed the capability to launch 2 fragments from the same gun at a range of velocities, and achieve impacts on an acceptor charge with good control over the spatial and temporal separation of the strikes. In this paper we will describe in detail the experimental techniques we have used, both to achieve the dual fragment launch and observe the acceptor charge response. In addition, we will describe the results obtained against PBX filled explosive targets; discuss the mechanisms controlling the target response and their significance for vulnerability assessment. Results of these tests have clearly indicated the potential for detonation upon the second strike, at velocities well below those needed for shock initiation by a single fragment.

Protein-observed (19)F-NMR for fragment screening, affinity quantification and druggability assessment.

Science.gov (United States)

Gee, Clifford T; Arntson, Keith E; Urick, Andrew K; Mishra, Neeraj K; Hawk, Laura M L; Wisniewski, Andrea J; Pomerantz, William C K

2016-08-01

NMR spectroscopy can be used to quantify the binding affinity between proteins and low-complexity molecules, termed 'fragments'; this versatile screening approach allows researchers to assess the druggability of new protein targets. Protein-observed (19)F-NMR (PrOF NMR) using (19)F-labeled amino acids generates relatively simple spectra that are able to provide dynamic structural information toward understanding protein folding and function. Changes in these spectra upon the addition of fragment molecules can be observed and quantified. This protocol describes the sequence-selective labeling of three proteins (the first bromodomains of Brd4 and BrdT, and the KIX domain of the CREB-binding protein) using commercially available fluorinated aromatic amino acids and fluorinated precursors as example applications of the method developed by our research group. Fragment-screening approaches are discussed, as well as Kd determination, ligand-efficiency calculations and druggability assessment, i.e., the ability to target these proteins using small-molecule ligands. Experiment times on the order of a few minutes and the simplicity of the NMR spectra obtained make this approach well-suited to the investigation of small- to medium-sized proteins, as well as the screening of multiple proteins in the same experiment.

Quarkonium Physics at a Fixed-Target Experiment Using the LHC Beams

Energy Technology Data Exchange (ETDEWEB)

Lansberg, J.P.; /Orsay, IPN; Brodsky, S.J.; /SLAC; Fleuret, F.; /Ecole Polytechnique; Hadjidakis, C.; /Orsay, IPN

2012-04-09

We outline the many quarkonium-physics opportunities offered by a multi-purpose fixed-target experiment using the p and Pb LHC beams extracted by a bent crystal. This provides an integrated luminosity of 0.5 fb{sup -1} per year on a typical 1cm-long target. Such an extraction mode does not alter the performance of the collider experiments at the LHC. With such a high luminosity, one can analyse quarkonium production in great details in pp, pd and pA collisions at {radical}s{sub NN} {approx_equal} 115 GeV and at {radical}s{sub NN} {approx_equal} 72 GeV in PbA collisions. In a typical pp (pA) run, the obtained quarkonium yields per unit of rapidity are 2-3 orders of magnitude larger than those expected at RHIC and about respectively 10 (70) times larger than for ALICE. In PbA, they are comparable. By instrumenting the target-rapidity region, the large negative-x{sub F} domain can be accessed for the first time, greatly extending previous measurements by Hera-B and E866. Such analyses should help resolving the quarkonium-production controversies and clear the way for gluon PDF extraction via quarkonium studies. The nuclear target-species versatility provides a unique opportunity to study nuclear matter and the features of the hot and dense matter formed in PbA collisions. A polarised proton target allows the study of transverse-spin asymmetries in J/{Psi} and {Upsilon} production, providing access to the gluon and charm Sivers functions.

Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

Science.gov (United States)

Anusuya, Shanmugam; Natarajan, Jeyakumar

2012-12-01

Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

The dynamical fate of self-gravitating disc fragments after tidal downsizing

Science.gov (United States)

Forgan, Duncan; Parker, Richard J.; Rice, Ken

2015-02-01

The gravitational instability model of planet/brown dwarf formation proposes that protostellar discs can fragment into objects with masses above a few Jupiter masses at large semimajor axis. Tidal downsizing may reduce both the object mass and semimajor axis. However, most studies of tidal downsizing end when the protostellar disc disperses, while the system is embedded in its parent star-forming region. To compare disc fragment descendants with exoplanet and brown dwarf observations, the subsequent dynamical evolution must be explored. We carry out N-body integrations of fragment-fragment scattering in multi-object star systems, and star systems embedded in substructured clusters. In both cases, we use initial conditions generated by population synthesis models of tidal downsizing. The scattering simulations produce a wide range of eccentricities. The ejection rate is around 25 per cent. The ejecta mass distribution is similar to that for all objects, with a velocity dispersion consistent with those produced by full hydrodynamic simulations. The semimajor axis distribution after scattering extends to parsec scales. In the cluster simulations, 13 per cent of the objects are ejected from their planetary system, and around 10 per cent experience significant orbit modification. A small number of objects are recaptured on high-eccentricity, high-inclination orbits. The velocity distribution of ejecta is similar to that produced by fragment-fragment scattering. If fragment-fragment scattering and cluster stripping act together, then disc fragmentation should be efficient at producing free-floating substellar objects, and hence characterizing the free-floating planet population will provide strong constraints on the frequency of disc fragmentation.

D meson production asymmetry, unfavored fragmentation, and consequences for prompt atmospheric neutrino production

Science.gov (United States)

Maciuła, Rafał; Szczurek, Antoni

2018-04-01

We consider unfavored light quark/antiquark to D meson fragmentation. We discuss nonperturbative effects for small transverse momenta. The asymmetry for D+ and D- production measured by the LHCb collaboration provides natural constraints on the parton (quark/antiquark) fragmentation functions. We find that already a fraction of q /q ¯→D fragmentation probability is sufficient to account for the measured asymmetry. We make predictions for similar asymmetry for neutral D mesons. Large D -meson production asymmetries are found for large xF which is related to dominance of light quark/antiquark q /q ¯→D fragmentation over the standard c →D fragmentation. As a consequence, prompt atmospheric neutrino flux at high neutrino energies can be much larger than for the conventional c →D fragmentation. The latter can constitute a sizeable background for the cosmic neutrinos claimed to be observed recently by the IceCube Observatory. Large rapidity-dependent D+/D- and D0/D¯0 asymmetries are predicted for low (√{s }=20 - 100 GeV ) energies. The q /q ¯→D fragmentation leads to enhanced production of D mesons at low energies. At √{s }=20 GeV the enhancement factor with respect to the conventional contribution is larger than a factor of five. In the considered picture the large-xF D mesons are produced dominantly via fragmentation of light quarks/antiquarks. Predictions for fixed target p + 4He collisions relevant for a fixed target LHCb experiment are presented.

Multi-target drugs: the trend of drug research and development.

Science.gov (United States)

Lu, Jin-Jian; Pan, Wei; Hu, Yuan-Jia; Wang, Yi-Tao

2012-01-01

Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.

Engineering design of the EURISOL multi-MW spallation target

CERN Document Server

Herrera-Martínez, A; Ashrafi-Nik, M; Samec, K; Freibergs, J; Platacis, E

2007-01-01

The European Isotope Separation On-Line Radioactive Ion Beam project (EURISOL) is set to design the 'next-generation' European Isotope Separation On-Line (ISOL) Radioactive Ion Beam (RIB) facility. It will extend and amplify current research on nuclear physics, nuclear astrophysics and fundamental interactions beyond the year 2010. In EURISOL, four target stations are foreseen, three direct targets of approximately 100 kW of beam power and one multi-MW target assembly, all driven by a high-power particle accelerator. In this high power target station, high-intensity RIBs of neutron-rich isotopes will be obtained by inducing fission in several actinide targets surrounding a liquid metal spallation neutron source. This article summarises the work carried out within Task 2 of the EURISOL Design Study, with special attention to the coupled neutronics of the mercury proton-to-neutron converter and the fission targets. The overall performance of the facility, which will sustain fast neutron fluxes of the order of 1...

ENGINEERING DESIGN OF THE EURISOL MULTI-MW SPALLATION TARGET

CERN Document Server

Adonai Herrera-Martinez*, Yacine Kadi, Morteza Ashrafi-Nik, Karel Samec, Janis Freibergs, Ernests Platacis

The European Isotope Separation On-Line Radioactive Ion Beam project (EURISOL) is set to design the ‘next-generation’ European Isotope Separation On-Line (ISOL) Radioactive Ion Beam (RIB) facility. It will extend and amplify current research on nuclear physics, nuclear astrophysics and fundamental interactions beyond the year 2010. In EURISOL, four target stations are foreseen, three direct targets of approximately 100 kW of beam power and one multi-MW target assembly, all driven by a high-power particle accelerator. In this high power target station, high-intensity RIBs of neutron-rich isotopes will be obtained by inducing fission in several actinide targets surrounding a liquid metal spallation neutron source. This article summarises the work carried out within Task 2 of the EURISOL Design Study, with special attention to the coupled neutronics of the mercury proton-to-neutron converter and the fission targets. The overall performance of the facility, which will sustain fast neutron fluxes of the order ...

AGS Spallation Target Experiment (ASTE) Collaboration

International Nuclear Information System (INIS)

Oyama, Yukio

1999-01-01

An experiment on mercury spallation target with high energy proton beam, called as the AGS Spallation Target Experiment (ASTE) Collaboration, has been performed at Alternating Gradient Synchrotron (AGS) of Brookhaven National Laboratory (BNL) in USA, in cooperation among the laboratories in Japan, Europe and USA. The experimental setup, scope and preliminary results are presented in the paper. (author)

Coincidence study of alpha particle fragmentation at E/sub alpha/ = 140 MeV

International Nuclear Information System (INIS)

Koontz, R.W.

1980-01-01

Results of an experimental study of the interaction of 140 MeV alpha particles with 90 Zr nuclei resulting in fragmentation of the alpha particle are reported. The experimental observations of the study are analyzed and are found to show that alpha particle breakup reactions leading to at least 4-body final states, composed of two charged alpha particle fragments, contribute significantly to the singles yield of charged fragments observed at a fixed forward angle. The conclusions are based on coincidence measurements where one charged fragment is detected at a small forward angle which remains fixed, while the second charged fragment is detected at a series of coplanar secondary angles. The largest coincidence charged particle yield for the multiparticle final state events results from 90 Zr(α,pp)X reactions, where both of the measured protons have energy distributions similar to the proton singles energy distributions. The second largest observed coincidence yield involving two charged fragments arises from 90 Zr(α,pd)X reactions, where the p and d fragments, as in the 90 Zr(α,pp)X reactions also have energy distribution similar to the singles energy distributions. Analysis of additional measurements, where alpha particle fragments at the fixed angle are detected in coincidence with evaporation and nonequilibrium particles at many coplanar angles, show that the alpha particle fragmentation reactions are also generally associated with large energy transfer to the target nucleus. A multiple scattering model of the fragmentation reaction is employed, in conjunction with the experimental observations, to estimate the cross sections for alpha particle fragmentation into multi-particle final states resulting in n, 2n, p, pp, d, dn, dp, t and 3 He fragments. The estimated total cross section for all fragmentation reactions is 755 mb or approximately 38% of the total reaction cross section for 140 MeV alpha particle interactions with 90 Zr

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin : Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry

NARCIS (Netherlands)

Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgos, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K. H.

2016-01-01

Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for

SAR Target Recognition via Local Sparse Representation of Multi-Manifold Regularized Low-Rank Approximation

Directory of Open Access Journals (Sweden)

Meiting Yu

2018-02-01

Full Text Available The extraction of a valuable set of features and the design of a discriminative classifier are crucial for target recognition in SAR image. Although various features and classifiers have been proposed over the years, target recognition under extended operating conditions (EOCs is still a challenging problem, e.g., target with configuration variation, different capture orientations, and articulation. To address these problems, this paper presents a new strategy for target recognition. We first propose a low-dimensional representation model via incorporating multi-manifold regularization term into the low-rank matrix factorization framework. Two rules, pairwise similarity and local linearity, are employed for constructing multiple manifold regularization. By alternately optimizing the matrix factorization and manifold selection, the feature representation model can not only acquire the optimal low-rank approximation of original samples, but also capture the intrinsic manifold structure information. Then, to take full advantage of the local structure property of features and further improve the discriminative ability, local sparse representation is proposed for classification. Finally, extensive experiments on moving and stationary target acquisition and recognition (MSTAR database demonstrate the effectiveness of the proposed strategy, including target recognition under EOCs, as well as the capability of small training size.

Adhesion of axolemmal fragments to Schwann cells: a signal- and target-specific process closely linked to axolemmal induction of Schwann cell mitosis

International Nuclear Information System (INIS)

Sobue, G.; Pleasure, D.

1985-01-01

Radioiodinated rat CNS axolemmal fragments adhered to cultured rat Schwann cells by a time-, temperature-, and concentration-dependent process independent of extracellular ionized calcium. Adhesion showed target and signal specificity; axolemmal fragments adhered to endoneurial or dermal fibroblasts to a much lesser extent than to Schwann cells, and plasma membrane fragments from skeletal muscle, erythrocytes, or PNS myelin adhered to Schwann cells to a lesser extent than did axolemmal fragments. Brief trypsinization removed 94 to 97% of bound radioactivity from Schwann cells previously incubated with 125 I-axolemmal fragments for up to 24 hr, indicating that adhesion was largely a surface phenomenon rather than the result of rapid internalization of axolemmal fragments by the Schwann cells. When adhesion was compared to the axolemmal mitogenic response of Schwann cells, the concentration of axolemmal fragments yielding half-maximal adhesion was the same as the concentration producing half-maximal stimulation of Schwann cell mitosis. Trypsin digestion, homogenization, or heating of axolemmal fragments before application to cultured Schwann cells diminished adhesion and axolemmal fragment-induced stimulation of Schwann cell mitosis in a parallel fashion. Whereas adhesion of axolemmal fragments to the surfaces of the cultured Schwann cells reached completion within 4 hr in this assay system, induction of Schwann cell mitosis by the fragments required contact with Schwann cells for a minimum of 6 to 8 hr and reached a maximum when the axolemmal fragments had adhered to the Schwann cells for 24 hr or more

Dynamics of NO2 dissociation. Study by resonance-enhanced multi-photon ionisation of energy distribution and of anisotropies in fragments

International Nuclear Information System (INIS)

Mons, Michel

1988-01-01

In this research thesis, the author reports the use of laser resonance-enhanced multi-photon ionization and of time-of-flight mass spectrometry for a detailed characterization of fragments produced by a photo-dissociation process. The author more particularly addressed the case of a NO 2 molecule excited at low energies above the dissociation threshold. In the first part, the author discusses issues and problems related to molecular photo-dissociation. In the second part, he presents the developed method and shows that the combined use of both techniques allows a precise characterisation of photo-fragments in terms of internal or translational energies as well as in terms of angle distributions. Finally, the author presents and discusses results obtained in the case of NO 2 [fr

Fragment screening of cyclin G-associated kinase by weak affinity chromatography.

Science.gov (United States)

Meiby, Elinor; Knapp, Stefan; Elkins, Jonathan M; Ohlson, Sten

2012-11-01

Fragment-based drug discovery (FBDD) has become a new strategy for drug discovery where lead compounds are evolved from small molecules. These fragments form low affinity interactions (dissociation constant (K(D)) = mM - μM) with protein targets, which require fragment screening methods of sufficient sensitivity. Weak affinity chromatography (WAC) is a promising new technology for fragment screening based on selective retention of fragments by a drug target. Kinases are a major pharmaceutical target, and FBDD has been successfully applied to several of these targets. In this work, we have demonstrated the potential to use WAC in combination with mass spectrometry (MS) detection for fragment screening of a kinase target-cyclin G-associated kinase (GAK). One hundred seventy fragments were selected for WAC screening by virtual screening of a commercial fragment library against the ATP-binding site of five different proteins. GAK protein was immobilized on a capillary HPLC column, and compound binding was characterized by frontal affinity chromatography. Compounds were screened in sets of 13 or 14, in combination with MS detection for enhanced throughput. Seventy-eight fragments (46 %) with K(D) < 200 μM were detected, including a few highly efficient GAK binders (K(D) of 2 μM; ligand efficiency = 0.51). Of special interest is that chiral screening by WAC may be possible, as two stereoisomeric fragments, which both contained one chiral center, demonstrated twin peaks. This ability, in combination with the robustness, sensitivity, and simplicity of WAC makes it a new method for fragment screening of considerable potential.

A generic approach for expanding homolog-targeted residue screening of sulfonamides using a fast matrix separation and class-specific fragmentation-dependent acquisition with a hybrid quadrupole-linear ion trap mass spectrometer

International Nuclear Information System (INIS)

Huang Chunlin; Guo Bin; Wang Xiaoying; Li Jie; Zhu Weitao; Chen Bo; Ouyang Shan; Yao Shouzhuo

2012-01-01

Highlights: ► Generic homolog-targeted screening approach for multi-residual sulfonamide analogs. ► Single-tube extraction/partitioning-multifunction adsorption cleanup for direct injection. ► Class-specific fragmentation for expanding coverage of N 4 -acetyl and N-OH metabolites. ► PreS–IDA–EPI in LC–QqLIT for simultaneous screening and confirmation of real samples. - Abstract: A generic and efficient homolog-targeted approach was used to expand screening and detection of target class of sulfonamides and structural analogs, based on a fast single-tube extraction/partitioning-multifunction adsorption cleanup (SEP/MAC) for class-specific fragmentation-dependent acquisition with a liquid chromatography–hybrid triple-quadrupole linear ion trap mass spectrometer (LC–QqLIT). By combining the two-stage process conducted in a single tube as one-pot protocol, the straightforward SEP/MAC procedure was optimized to offer clean extracts with reasonable recovery (71–109% with RSDs 4 -acetyl and hydroxylamine metabolites plus their possible dimers. Moreover, the PreS-triggered automatically enhanced product ion spectral acquisition enabled simultaneous screening, profiling and confirmation of an unlimited number of analytes belonging to the sulfonamide class within a single analysis. The validation and application results of the generic SEP/MAC-based LC–QqLIT strategy consistently demonstrated favorable performances with acceptable accuracy (67–116%), precision (RSDs −1 ) to meet the acceptance criteria for all the sulfonamide–tissue combinations. Thus, the integration of the matrix-independent SEP/MAC procedure and the multiparameter matching algorithm with the unit-resolution LC–QqLIT instrument can serve as a valuable semi-targeted discovery strategy for rapid screening and reliable quantitative/confirmatory analysis of real samples.

Dimensional crossover in fragmentation

Science.gov (United States)

Sotolongo-Costa, Oscar; Rodriguez, Arezky H.; Rodgers, G. J.

2000-11-01

Experiments in which thick clay plates and glass rods are fractured have revealed different behavior of fragment mass distribution function in the small and large fragment regions. In this paper we explain this behavior using non-extensive Tsallis statistics and show how the crossover between the two regions is caused by the change in the fragments’ dimensionality during the fracture process. We obtain a physical criterion for the position of this crossover and an expression for the change in the power-law exponent between the small and large fragment regions. These predictions are in good agreement with the experiments on thick clay plates.

Multicharged Ion-induced simple molecule fragmentation dynamics

International Nuclear Information System (INIS)

Tarisien, M.

2003-10-01

The aim of this work is to study the dynamics of swift multicharged ion-induced fragmentation of diatomic (CO) and triatomic (CO 2 ) molecules. Performed at the GANIL facility, this study used the Recoil Ion Momentum Spectroscopy technique (RIMS), which consists of a time-of-flight mass spectrometer, coupled with a multi-hit capability position sensitive detector (delay line anode). The high-resolution measurement of the kinetic energy distribution released (KER) during the CO fragmentation points out the limitation of the Coulomb Explosion Model, revealing, for example, the di-cation CO 2 + electronic state contribution in the case of C + /O + fragmentation pathway. Furthermore, the multi-ionization cross section dependence with the orientation of the internuclear axis of CO is compared with a geometrical model calculation. Finally, different behaviours are observed for the dissociation dynamics of a triatomic molecule (CO 2 ). While triple ionization leads mainly to a synchronous concerted fragmentation dynamics, a weak fraction of dissociating molecule follows a sequential dynamics involving CO 2 + metastable states. In the case of double ionization, (CO 2 ) 2+ di-cation dissociation dynamics is asynchronously concerted and has been interpreted using a simple model involving an asymmetrical vibration of the molecule. (author)

Spatial- and Time-Correlated Detection of Fission Fragments

Directory of Open Access Journals (Sweden)

Platkevic M.

2012-02-01

Full Text Available With the goal to measure angular correlations of fission fragments in rare fission decay (e.g. ternary and quaternary fission, a multi-detector coincidence system based on two and up to four position sensitive pixel detectors Timepix has been built. In addition to the high granularity, wide dynamic range and per pixel signal threshold, these devices are equipped with per pixel energy and time sensitivity providing more information (position, energy, time, enhances particle-type identification and selectivity of event-by-event detection. Operation of the device with the integrated USB 2.0 based readout interface FITPix and the control and data acquisition software tool Pixelman enables online visualization and flexible/adjustable operation for a different type of experiments. Spatially correlated fission fragments can be thus registered in coincidence. Similarly triggered measurements are performed using an integrated spectrometric module with analogue signal chain electronics. The current status of development together with demonstration of the technique with a 252Cf source is presented.

SKI2 mediates degradation of RISC 5'-cleavage fragments and prevents secondary siRNA production from miRNA targets in Arabidopsis.

Science.gov (United States)

Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter

2015-12-15

Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20-24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5', but not 3'-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5' to the cleavage site, but several examples of 3'-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5'-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5'-cleavage fragments. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

EURISOL-DS Overall Design of the Multi-MW Target Station

CERN Document Server

Olivier Choisnet, Cyril Kharoua, Yacine Kadi, Karel Samec (CERN)

The EURISOL Design Study investigated the feasibility of a complex instrument to push back the boundaries of current physics knowledge amidst today’s ever-increasing need for realism due to constraints imposed by safety, performance and, not least, budgetary responsibility.In order to attend to these concerns, the EURISOL Multi-Megawatt converter target, its associated fission targets and the three 100 kW direct targets are all integrated into a single facility housing the ancillary equipment as well. The overall layout of the facility, its functional break-down and the main modes of operation are presented in the current report.

Rational drug design for anti-cancer chemotherapy: multi-target QSAR models for the in silico discovery of anti-colorectal cancer agents.

Science.gov (United States)

Speck-Planche, Alejandro; Kleandrova, Valeria V; Luan, Feng; Cordeiro, M Natália D S

2012-08-01

The discovery of new and more potent anti-cancer agents constitutes one of the most active fields of research in chemotherapy. Colorectal cancer (CRC) is one of the most studied cancers because of its high prevalence and number of deaths. In the current pharmaceutical design of more efficient anti-CRC drugs, the use of methodologies based on Chemoinformatics has played a decisive role, including Quantitative-Structure-Activity Relationship (QSAR) techniques. However, until now, there is no methodology able to predict anti-CRC activity of compounds against more than one CRC cell line, which should constitute the principal goal. In an attempt to overcome this problem we develop here the first multi-target (mt) approach for the virtual screening and rational in silico discovery of anti-CRC agents against ten cell lines. Here, two mt-QSAR classification models were constructed using a large and heterogeneous database of compounds. The first model was based on linear discriminant analysis (mt-QSAR-LDA) employing fragment-based descriptors while the second model was obtained using artificial neural networks (mt-QSAR-ANN) with global 2D descriptors. Both models correctly classified more than 90% of active and inactive compounds in training and prediction sets. Some fragments were extracted from the molecules and their contributions to anti-CRC activity were calculated using mt-QSAR-LDA model. Several fragments were identified as potential substructural features responsible for the anti-CRC activity and new molecules designed from those fragments with positive contributions were suggested and correctly predicted by the two models as possible potent and versatile anti-CRC agents. Copyright © 2012 Elsevier Ltd. All rights reserved.

Projectile fragmentation of neutron-rich nuclei on light target (momentum distribution and nucleon-removal cross section)

International Nuclear Information System (INIS)

Kobayashi, T.; Tanihata, I.; Suzuki, T.

1992-01-01

Transverse momentum distributions of the projectile fragments from β-unstable nuclei have been measured with various projectile and target combinations. The momentum correlation of two neutrons in the neutron halo is extracted from the P c t distribution of 9 Li and hat of the neutrons. It is found that the two neutrons are moving in the same direction on average and thus strongly suggests the formation of a di-neutron in 11 Li. (Author)

On the fragmentation of asteroids and planetary satellites

International Nuclear Information System (INIS)

Housen, K.R.; Holsapple, K.A.

1990-01-01

A general scaling model is defined which allows the extrapolation of small-scale collisional fragmentation experiment results, and existing collisional theories are considered within its framework. Scaling based exclusively upon the specific energy, Q, of the event (the ratio of projectile kinetic energy to the mass of the target body) is shown to hold when (1) the projectile and target material properties do not depend on size or time scales, and (2) the collision is governed by kinetic energy independently of impact velocity. Because neither of these conditions should hold, serious doubt is cast on the validity of Q's use as the sole scaling parameter. 43 refs

The FIRST experiment at GSI

International Nuclear Information System (INIS)

Pleskac, R.; Abou-Haidar, Z.; Agodi, C.; Alvarez, M.A.G.; Aumann, T.; Battistoni, G.; Bocci, A.; Böhlen, T.T.; Boudard, A.; Brunetti, A.; Carpinelli, M.; Cirrone, G.A.P.; Cortes-Giraldo, M.A.; Cuttone, G.; De Napoli, M.; Durante, M.; Fernández-García, J.P.; Finck, C.; Golosio, B.; Gallardo, M.I.

2012-01-01

The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at the SIS accelerator of GSI laboratory in Darmstadt has been designed for the measurement of ion fragmentation cross-sections at different angles and energies between 100 and 1000 MeV/nucleon. Nuclear fragmentation processes are relevant in several fields of basic research and applied physics and are of particular interest for tumor therapy and for space radiation protection applications. The start of the scientific program of the FIRST experiment was on summer 2011 and was focused on the measurement of 400 MeV/nucleon 12 C beam fragmentation on thin (8 mm) graphite target. The detector is partly based on an already existing setup made of a dipole magnet (ALADiN), a time projection chamber (TP-MUSIC IV), a neutron detector (LAND) and a time of flight scintillator system (TOFWALL). This pre-existing setup has been integrated with newly designed detectors in the Interaction Region, around the carbon target placed in a sample changer. The new detectors are a scintillator Start Counter, a Beam Monitor drift chamber, a silicon Vertex Detector and a Proton Tagger scintillator system optimized for the detection of light fragments emitted at large angles. In this paper we review the experimental setup, then we present the simulation software, the data acquisition system and finally the trigger strategy of the experiment.

The FIRST experiment at GSI

Energy Technology Data Exchange (ETDEWEB)

Pleskac, R. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Abou-Haidar, Z. [CNA, Sevilla (Spain); Agodi, C. [Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (Italy); Alvarez, M.A.G. [CNA, Sevilla (Spain); Aumann, T. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Battistoni, G. [Istituto Nazionale di Fisica Nucleare - Sezione di Milano (Italy); Bocci, A. [CNA, Sevilla (Spain); Boehlen, T.T. [European Organization for Nuclear Research CERN, Geneva (Switzerland); Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm (Sweden); Boudard, A. [CEA-Saclay, IRFU/SPhN, Gif sur Yvette Cedex (France); Brunetti, A.; Carpinelli, M. [Istituto Nazionale di Fisica Nucleare - Sezione di Cagliari (Italy); Universita' di Sassari (Italy); Cirrone, G.A.P. [Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (Italy); Cortes-Giraldo, M.A. [Departamento de Fisica Atomica, Molecular y Nuclear, University of Sevilla, 41080-Sevilla (Spain); Cuttone, G. [Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (Italy); De Napoli, M. [Istituto Nazionale di Fisica Nucleare - Sezione di Catania (Italy); Durante, M. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Fernandez-Garcia, J.P. [Departamento de Fisica Atomica, Molecular y Nuclear, University of Sevilla, 41080-Sevilla (Spain); Finck, C. [Institut Pluridisciplinaire Hubert Curien, Strasbourg (France); Golosio, B. [Istituto Nazionale di Fisica Nucleare - Sezione di Cagliari (Italy); Universita' di Sassari (Italy); Gallardo, M.I. [Departamento de Fisica Atomica, Molecular y Nuclear, University of Sevilla, 41080-Sevilla (Spain); and others

2012-06-21

The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at the SIS accelerator of GSI laboratory in Darmstadt has been designed for the measurement of ion fragmentation cross-sections at different angles and energies between 100 and 1000 MeV/nucleon. Nuclear fragmentation processes are relevant in several fields of basic research and applied physics and are of particular interest for tumor therapy and for space radiation protection applications. The start of the scientific program of the FIRST experiment was on summer 2011 and was focused on the measurement of 400 MeV/nucleon {sup 12}C beam fragmentation on thin (8 mm) graphite target. The detector is partly based on an already existing setup made of a dipole magnet (ALADiN), a time projection chamber (TP-MUSIC IV), a neutron detector (LAND) and a time of flight scintillator system (TOFWALL). This pre-existing setup has been integrated with newly designed detectors in the Interaction Region, around the carbon target placed in a sample changer. The new detectors are a scintillator Start Counter, a Beam Monitor drift chamber, a silicon Vertex Detector and a Proton Tagger scintillator system optimized for the detection of light fragments emitted at large angles. In this paper we review the experimental setup, then we present the simulation software, the data acquisition system and finally the trigger strategy of the experiment.

The FIRST experiment at GSI

Science.gov (United States)

Pleskac, R.; Abou-Haidar, Z.; Agodi, C.; Alvarez, M. A. G.; Aumann, T.; Battistoni, G.; Bocci, A.; Böhlen, T. T.; Boudard, A.; Brunetti, A.; Carpinelli, M.; Cirrone, G. A. P.; Cortes-Giraldo, M. A.; Cuttone, G.; De Napoli, M.; Durante, M.; Fernández-García, J. P.; Finck, C.; Golosio, B.; Gallardo, M. I.; Iarocci, E.; Iazzi, F.; Ickert, G.; Introzzi, R.; Juliani, D.; Krimmer, J.; Kurz, N.; Labalme, M.; Leifels, Y.; Le Fevre, A.; Leray, S.; Marchetto, F.; Monaco, V.; Morone, M. C.; Oliva, P.; Paoloni, A.; Piersanti, L.; Quesada, J. M.; Raciti, G.; Randazzo, N.; Romano, F.; Rossi, D.; Rousseau, M.; Sacchi, R.; Sala, P.; Sarti, A.; Scheidenberger, C.; Schuy, C.; Sciubba, A.; Sfienti, C.; Simon, H.; Sipala, V.; Spiriti, E.; Stuttge, L.; Tropea, S.; Younis, H.; Patera, V.

2012-06-01

The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at the SIS accelerator of GSI laboratory in Darmstadt has been designed for the measurement of ion fragmentation cross-sections at different angles and energies between 100 and 1000 MeV/nucleon. Nuclear fragmentation processes are relevant in several fields of basic research and applied physics and are of particular interest for tumor therapy and for space radiation protection applications. The start of the scientific program of the FIRST experiment was on summer 2011 and was focused on the measurement of 400 MeV/nucleon 12C beam fragmentation on thin (8 mm) graphite target. The detector is partly based on an already existing setup made of a dipole magnet (ALADiN), a time projection chamber (TP-MUSIC IV), a neutron detector (LAND) and a time of flight scintillator system (TOFWALL). This pre-existing setup has been integrated with newly designed detectors in the Interaction Region, around the carbon target placed in a sample changer. The new detectors are a scintillator Start Counter, a Beam Monitor drift chamber, a silicon Vertex Detector and a Proton Tagger scintillator system optimized for the detection of light fragments emitted at large angles. In this paper we review the experimental setup, then we present the simulation software, the data acquisition system and finally the trigger strategy of the experiment.

Multifactorial Understanding of Ion Abundance in Tandem Mass Spectrometry Experiments.

Science.gov (United States)

Fazal, Zeeshan; Southey, Bruce R; Sweedler, Jonathan V; Rodriguez-Zas, Sandra L

2013-01-29

In a bottom-up shotgun approach, the proteins of a mixture are enzymatically digested, separated, and analyzed via tandem mass spectrometry. The mass spectra relating fragment ion intensities (abundance) to the mass-to-charge are used to deduce the amino acid sequence and identify the peptides and proteins. The variables that influence intensity were characterized using a multi-factorial mixed-effects model, a ten-fold cross-validation, and stepwise feature selection on 6,352,528 fragment ions from 61,543 peptide ions. Intensity was higher in fragment ions that did not have neutral mass loss relative to any mass loss or that had a +1 charge state. Peptide ions classified for proton mobility as non-mobile had lowest intensity of all mobility levels. Higher basic residue (arginine, lysine or histidine) counts in the peptide ion and low counts in the fragment ion were associated with lower fragment ion intensities. Higher counts of proline in peptide and fragment ions were associated with lower intensities. These results are consistent with the mobile proton theory. Opposite trends between peptide and fragment ion counts and intensity may be due to the different impact of factor under consideration at different stages of the MS/MS experiment or to the different distribution of observations across peptide and fragment ion levels. Presence of basic residues at all three positions next to the fragmentation site was associated with lower fragment ion intensity. The presence of proline proximal to the fragmentation site enhanced fragmentation and had the opposite trend when located distant from the site. A positive association between fragment ion intensity and presence of sulfur residues (cysteine and methionine) on the vicinity of the fragmentation site was identified. These results highlight the multi-factorial nature of fragment ion intensity and could improve the algorithms for peptide identification and the simulation in tandem mass spectrometry experiments.

DNA fragmentation: manifestation of target cell destruction mediated by cytotoxic T-cell lines, lymphotoxin-secreting helper T-cell clones, and cell-free lymphotoxin-containing supernatant

International Nuclear Information System (INIS)

Schmid, D.S.; Tite, J.P.; Ruddle, N.H.

1986-01-01

A Lyt-2 + , trinitrophenyl-specific, lymphotoxin-secreting, cytotoxic T-cell line, PCl 55, mediates the digestion of target cell DNA into discretely sized fragments. This phenomenon manifests itself within 30 min after effector cell encounter as measured by the release of 3 H counts from target cells prelabeled with [ 3 H]deoxythymidine and occurs even at very low effector to target cell ratios (0.25:1). A Lyt-1 + , ovalbumin-specific, lymphotoxin-secreting T-helper cell clone, 5.9.24, is also able to mediate fragmentation of target cell DNA over a time course essentially indistinguishable from the cytotoxic T lymphocyte-mediated hit. Cell-free lymphotoxin-containing supernatants also cause release of DNA from targets, although they require a longer time course, on the order of 24 hr. In contrast, lysis of cells by antibody plus complement or Triton X-100 does not result in DNA release even after extended periods of incubation (24 hr). All three treatments that result in the release of DNA from cells cause fragmentation of that DNA into discretely sized pieces that are multiples of 200 base pairs. The results thus suggest that cytotoxic T cells, lymphotoxin-secreting helper clones with cytolytic activity, and lymphotoxin all effect target cell destruction by means of a similar mechanism and that observed differences in time course and the absence of target cell specificity in killing mediated by lymphotoxin may simply reflect differences in the mode of toxin delivery

Fragment library design: using cheminformatics and expert chemists to fill gaps in existing fragment libraries.

Science.gov (United States)

Kutchukian, Peter S; So, Sung-Sau; Fischer, Christian; Waller, Chris L

2015-01-01

Fragment based screening (FBS) has emerged as a mainstream lead discovery strategy in academia, biotechnology start-ups, and large pharma. As a prerequisite of FBS, a structurally diverse library of fragments is desirable in order to identify chemical matter that will interact with the range of diverse target classes that are prosecuted in contemporary screening campaigns. In addition, it is also desirable to offer synthetically amenable starting points to increase the probability of a successful fragment evolution through medicinal chemistry. Herein we describe a method to identify biologically relevant chemical substructures that are missing from an existing fragment library (chemical gaps), and organize these chemical gaps hierarchically so that medicinal chemists can efficiently navigate the prioritized chemical space and subsequently select purchasable fragments for inclusion in an enhanced fragment library.

Cooperative motion control for multi-target observation

Energy Technology Data Exchange (ETDEWEB)

Parker, L.E.

1997-08-01

An important issue that arises in the automation of many security, surveillance, and reconnaissance tasks is that of monitoring (or observing) the movements of targets navigating in a bounded area of interest. A key research issue in these problems is that of sensor placement--determining where sensors should be located to maintain the targets in view. In complex applications involving limited-range sensors, the use of multiple sensors dynamically moving over time is required. In this paper, the author investigates the use of a cooperative team of autonomous sensor-based robots for the observation of multiple moving targets. The focus is primarily on developing the distributed control strategies that allow the robot team to attempt to minimize the total time in which targets escape observation by some robot team member in the area of interest. This paper first formalizes the problem and discusses related work. The author then presents a distributed approximate approach to solving this problem that combines low-level multi-robot control with higher-level reasoning control based on the ALLIANCE formalism. The effectiveness of the approach is analyzed by comparing it to three other feasible algorithms for cooperative control, showing the superiority of the approach for a large class of problems.

Cooperative motion control for multi-target observation

International Nuclear Information System (INIS)

Parker, L.E.

1997-01-01

An important issue that arises in the automation of many security, surveillance, and reconnaissance tasks is that of monitoring (or observing) the movements of targets navigating in a bounded area of interest. A key research issue in these problems is that of sensor placement--determining where sensors should be located to maintain the targets in view. In complex applications involving limited-range sensors, the use of multiple sensors dynamically moving over time is required. In this paper, the author investigates the use of a cooperative team of autonomous sensor-based robots for the observation of multiple moving targets. The focus is primarily on developing the distributed control strategies that allow the robot team to attempt to minimize the total time in which targets escape observation by some robot team member in the area of interest. This paper first formalizes the problem and discusses related work. The author then presents a distributed approximate approach to solving this problem that combines low-level multi-robot control with higher-level reasoning control based on the ALLIANCE formalism. The effectiveness of the approach is analyzed by comparing it to three other feasible algorithms for cooperative control, showing the superiority of the approach for a large class of problems

Evaluation of tumor targeting with radiolabeled F(ab2 fragment of a humanized monoclonal antibody

Directory of Open Access Journals (Sweden)

"Babaei MH

2002-08-01

Full Text Available Humanized monoclonal antibody U36 and its F(ab'2 fragment, radio labeled with 125I, were tested for tumor localization in nude mice bearing a squamous cell carcinoma xenograft line derived from a head and neck carcinoma. Monoclonal antibody IgG or F(ab'2 fragment were injected in parallel and at days 1, 2 and 3, mice were dissected for determination of isotope biodistribution. IgG as well as F(ab'2 showed highly specific localization in tumor tissue. The mean tumor uptake (n=3 is expressed as the percentage of the injected dose per gram of tumor tissue (%ID/g. %ID/g of IgG was 11.7% at day 1 and decreased to 10.9% at day 3 whereas %ID/g of F(ab'2 was 2.9% at day 1 and decreased on following days. Tumor to blood ratios (T/B at day 1 were 0.86 for IgG and 1.32 for F(ab'2 and reached a maximum at day 3 with values of 4.41 and 1.84 respectively. These findings suggest that the superior tumor to non-tumor ratios in the day of 1 render the F(ab'2 fragment more qualified for specific targeting radioisotopes to tumor xenografts in this exprimental setting.

The VERDI fission fragment spectrometer

Directory of Open Access Journals (Sweden)

Frégeau M.O.

2013-12-01

Full Text Available The VERDI time-of-flight spectrometer is dedicated to measurements of fission product yields and of prompt neutron emission data. Pre-neutron fission-fragment masses will be determined by the double time-of-flight (TOF technique. For this purpose an excellent time resolution is required. The time of flight of the fragments will be measured by electrostatic mirrors located near the target and the time signal coming from silicon detectors located at 50 cm on both sides of the target. This configuration, where the stop detector will provide us simultaneously with the kinetic energy of the fragment and timing information, significantly limits energy straggling in comparison to legacy experimental setup where a thin foil was usually used as a stop detector. In order to improve timing resolution, neutron transmutation doped silicon will be used. The high resistivity homogeneity of this material should significantly improve resolution in comparison to standard silicon detectors. Post-neutron fission fragment masses are obtained form the time-of-flight and the energy signal in the silicon detector. As an intermediary step a diamond detector will also be used as start detector located very close to the target. Previous tests have shown that poly-crystalline chemical vapour deposition (pCVD diamonds provides a coincidence time resolution of 150 ps not allowing complete separation between very low-energy fission fragments, alpha particles and noise. New results from using artificial single-crystal diamonds (sCVD show similar time resolution as from pCVD diamonds but also sufficiently good energy resolution.

Data acquisition for experiments with multi-detector arrays

Indian Academy of Sciences (India)

Experiments with multi-detector arrays have special requirements and place higher demands on computer data acquisition systems. In this contribution we discuss data acquisition systems with special emphasis on multi-detector arrays and in particular we describe a new data acquisition system, AMPS which we have ...

Large fragment production calculations in relativistic heavy-ion reactions

International Nuclear Information System (INIS)

Seixas de Oliveira, L.F.

1978-12-01

The abrasion-ablation model is briefly described and then used to calculate cross sections for production of large fragments resulting from target or projectile fragmentation in high-energy heavy-ion collisions. The number of nucleons removed from the colliding nuclei in the abrasion stage and the excitation energy of the remaining fragments (primary products) are calculated with the geometrical picture of two different models: the fireball and the firestreak models. The charge-to-mass dispersion of the primary products is calculated using either a model which assumes no correlations between proton and neutron positions inside the nucleus (hypergeometric distribution) or a model based upon the zero-point oscillations of the giant dipole resonance (NUC-GDR). Standard Weisskopf--Ewing statistical evaporation calculations are used to calculate final product distributions. Results of the pure abrasion-ablation model are compared with a variety of experimental data. The comparisons show the insufficiency of the extra-surface energy term used in the abrasion calculations. A frictional spectator interaction (FSI) is introduced which increases the average excitation energy of the primary products, and improves the results considerably in most cases. Agreements and discrepancies of the results calculated with the different theoretical assumptions and the experimental data are studied. Of particular relevance is the possibility of observing nuclear ground-state correlations.Results of the recently completed experiment of fragmentation of 213 Mev/A 40 Ar projectiles are studied and shown not to be capable of answering that question unambiguously. But predictions for the upcoming 48 Ca fragmentation experiment clearly show the possibility of observing correlation effects. 78 references

A PZT Actuated Triple-Finger Gripper for Multi-Target Micromanipulation

Directory of Open Access Journals (Sweden)

Tao Chen

2017-01-01

Full Text Available This paper presents a triple-finger gripper driven by a piezoceramic (PZT transducer for multi-target micromanipulation. The gripper consists of three fingers assembled on adjustable pedestals with flexible hinges for a large adjustable range. Each finger has a PZT actuator, an amplifying structure, and a changeable end effector. The moving trajectories of single and double fingers were calculated and finite element analyses were performed to verify the reliability of the structures. In the gripping experiment, various end effectors of the fingers such as tungsten probes and fibers were tested, and different micro-objects such as glass hollow spheres and iron spheres with diameters ranging from 10 to 800 μm were picked and released. The output resolution is 145 nm/V, and the driven displacement range of the gripper is 43.4 μm. The PZT actuated triple-finger gripper has superior adaptability, high efficiency, and a low cost.

Effects of target shape and impact speed on the outcome of catastrophic disruptions

Science.gov (United States)

Campo~Bagatin, A.; Durda, D.; Alemañ, R.; Flynn, G.; Strait, M.; Clayton, A.; Patmore, E.

2014-07-01

Because of the propensity of previous laboratory investigations to focus on idealized spherical targets, there is a bit of ambiguity in decoupling the relative importance/influence of low speed or spherical shape in producing the 'onion shell' fragment shape outcomes found in impacts into spherical targets [1,2]. If due primarily to impact speed/energy density as suggested by [3], this could play an important role in main-belt impacts due to the presence of non-spherical targets and non-negligible probability of low-speed (i.e., below about 3-4 km/s, subsonic in rock) impacts [4]. Also, [5] and [6] suggested that the shape of targets may affect the outcome of shattering processes, both in terms of fragment shape and mass distribution. To examine explicitly the effects of target shape in impact outcomes, we chose to conduct impact experiments on both spherical and naturally-occurring irregularly-shaped basalt targets. We impacted a total of six targets (two spheres and four irregular targets). We focused on shots with impact speeds in the ˜4 to 6 km/s range by 3/16th-inch diameter Al-sphere projectiles fired at the NASA AVGR. Following each shot, the debris were recovered (>95 %) and large fragments (>0.20 g) were individually weighed, allowing us to carefully measure the mass-frequency distribution from each impact experiment. The 36 largest fragments of each shot were photographed and their largest axes accurately measured by the program ''ImageJ''. Their shortest axes were measured by means of a digital caliber. High-speed video of each impact was obtained to aid interpretation of the fragmentation mode of the targets. Images clearly show that shell-like fragments can be produced in shattering events not in the target's surface. Instead, those fragments may form around the core, well inside the target structure, independently on the target shape itself. This is a feature not reported to date. In order to understand what the bulk macro-porosity of a non

Coincidence measurement between α-particles and projectile-like fragments in the reaction of 82.7 MeV 16O on 27Al

International Nuclear Information System (INIS)

Shen Wenqing; Zhan Wenlong; Zhu Yongtai

1988-01-01

In a coincidence measurement between α-particles and projectile-like fragments in the reaction of 82.7 MeV 16 O on 27 Al, the contour plot of Galilean-invariant cross section of the coincidence between C-fragments and α-particles in the velocity plane, and the coincident angular correlation have been obtained. The correlated α-particles measured at positive angles (on the same side of the beam as the projectile-like fragments) were emitted mainly from the projectile-like fragments;the α-particles at large negative angles were emitted from the target-like fragments;the α-particles at small negative angles came from the fragmentation of the 16 O projectile. A possible reaction mechanism in which the residue produced in the fragmentation of the projectile continues the dissipation process during the interaction with the target has been discussed. It is also pointed out that in the large yield of C-fragments observed in the inclusive experiment, the contribution of C-fragments produced by the excited 16 O of DIC product via α-emission is quite small

Davisson-Germer Prize in Atomic or Surface Physics: The COLTRIMS multi-particle imaging technique-new Insight into the World of Correlation

Science.gov (United States)

Schmidt-Bocking, Horst

2008-05-01

The correlated many-particle dynamics in Coulombic systems, which is one of the unsolved fundamental problems in AMO-physics, can now be experimentally approached with so far unprecedented completeness and precision. The recent development of the COLTRIMS technique (COLd Target Recoil Ion Momentum Spectroscopy) provides a coincident multi-fragment imaging technique for eV and sub-eV fragment detection. In its completeness it is as powerful as the bubble chamber in high energy physics. In recent benchmark experiments quasi snapshots (duration as short as an atto-sec) of the correlated dynamics between electrons and nuclei has been made for atomic and molecular objects. This new imaging technique has opened a powerful observation window into the hidden world of many-particle dynamics. Recent multiple-ionization studies will be presented and the observation of correlated electron pairs will be discussed.

Process of Fragment-Based Lead Discovery—A Perspective from NMR

Directory of Open Access Journals (Sweden)

Rongsheng Ma

2016-07-01

Full Text Available Fragment-based lead discovery (FBLD has proven fruitful during the past two decades for a variety of targets, even challenging protein–protein interaction (PPI systems. Nuclear magnetic resonance (NMR spectroscopy plays a vital role, from initial fragment-based screening to lead generation, because of its power to probe the intrinsically weak interactions between targets and low-molecular-weight fragments. Here, we review the NMR FBLD process from initial library construction to lead generation. We describe technical aspects regarding fragment library design, ligand- and protein-observed screening, and protein–ligand structure model generation. For weak binders, the initial hit-to-lead evolution can be guided by structural information retrieved from NMR spectroscopy, including chemical shift perturbation, transferred pseudocontact shifts, and paramagnetic relaxation enhancement. This perspective examines structure-guided optimization from weak fragment screening hits to potent leads for challenging PPI targets.

Isotopic production cross-sections and recoil velocities of spallation-fission fragments in the reaction 238U(1A GeV)+e

CERN Document Server

Pereira, J; Wlazlo, W; Benlliure, J; Casarejos, E; Armbruster, P; Bernas, M; Enqvist, T; Legrain, R; Leray, S; Rejmund, F; Mustapha, B; Schmidt, K.-H; Stéphan, C; Taïeb, J; Tassan-Got, L; Volant, C; Boudard, A; Czajkowski, S; 10.1103/PhysRevC.75.014602

2007-01-01

Fission fragments of 1A GeV 238U nuclei interacting with a deuterium target have been investigatedwith the Fragment Separator (FRS) at GSI (Darmstadt) by measuring their isotopicproduction cross-sections and recoil velocities. The results, along with those obtained recently forspallation-evaporation fragments, provide a comprehensive analysis of the spallation nuclear productionsin the reaction 238U(1A GeV)+d. Details about experiment performance, data reductionand results will be presented.

Light fragment production at forward angles in Ne and Ar induced reactions

International Nuclear Information System (INIS)

Alard, J.P.; Biagi, F.; Morel, P.; Bastid, N.; Augerat, J.; Charmensat, P.; Crouau, M.; Dupieux, P.; Fraysse, L.; Marroncle, J.; Brochard, F.; Gorodetzky, P.; Racca, C.

1990-01-01

The results of the experiments performed at Saturne, in order to investigate light fragment emission at small angles, are reported. The measurements were performed using a plastic wall associated with the Diogene pictorial drift chamber. Different selected multiplicities in the central chamber are applied. The exclusive measurements are reported both for Ne and Ar projectiles on several targets

SKI2 mediates degradation of RISC 5′-cleavage fragments and prevents secondary siRNA production from miRNA targets in Arabidopsis

Science.gov (United States)

Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter

2015-01-01

Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20–24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5′, but not 3′-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5′ to the cleavage site, but several examples of 3′-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5′-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5′-cleavage fragments. PMID:26464441

Experiences with Interactive Multi-touch Tables

NARCIS (Netherlands)

Fikkert, F.W.; Hakvoort, M.; Hakvoort, M.C.; van der Vet, P.E.; Nijholt, Antinus; Nijholt, A.; Reidsma, D.; Reidsma, Dennis; Hondorp, G.H.W.

2009-01-01

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

Deliverable D5: The Multi-Megawatt Target Station (Final Report)

CERN Document Server

Karel Samec et al. (CERN, IPUL, ITN, PSI)

The Eurisol initiative seeks to develop an isotope production facility to provide the scientific community with the means to achieving high yields of isotopes and extending the variety of isotopes thus produced towards more exotic types rarely seen in existing facilities.The Multi-MW converter target at the heart of the projected facility is designed to create isotopes by fissioning uranium carbide (UC) target arranged coaxially around a 4 MW converter target. It is therefore essential that the target be as compact as possible to avoid losing neutrons to capture whilst maximising the neutron flux to enhance the number of fissions per second in the UC targets.The proposed ISOL facility would use both (a) several 100 kW proton beams on a thick solid target to produceRIBs directly, and (b) a liquid metal 4 MW ‘converter’ target to release high fluxes of spallation neutrons which would then produce RIBs by fission in a secondary uranium carbide (UCx) target. An alternative windowless liquid mercury-jet ‘con...

A Multi-targeted Approach to Suppress Tumor-Promoting Inflammation

Science.gov (United States)

Samadi, Abbas K.; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Bishayee, Anupam; Lokeshwar, Bal L.; Grue, Brendan; Panis, Carolina; Boosani, Chandra S.; Poudyal, Deepak; Stafforini, Diana M.; Bhakta, Dipita; Niccolai, Elena; Guha, Gunjan; Rupasinghe, H.P. Vasantha; Fujii, Hiromasa; Honoki, Kanya; Mehta, Kapil; Aquilano, Katia; Lowe, Leroy; Hofseth, Lorne J.; Ricciardiello, Luigi; Ciriolo, Maria Rosa; Singh, Neetu; Whelan, Richard L.; Chaturvedi, Rupesh; Ashraf, S. Salman; Kumara, HMC Shantha; Nowsheen, Somaira; Mohammed, Sulma I.; Helferich, William G.; Yang, Xujuan

2015-01-01

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes. PMID:25951989

Stochastic weighted particle methods for population balance equations with coagulation, fragmentation and spatial inhomogeneity

International Nuclear Information System (INIS)

Lee, Kok Foong; Patterson, Robert I.A.; Wagner, Wolfgang; Kraft, Markus

2015-01-01

Graphical abstract: -- Highlights: •Problems concerning multi-compartment population balance equations are studied. •A class of fragmentation weight transfer functions is presented. •Three stochastic weighted algorithms are compared against the direct simulation algorithm. •The numerical errors of the stochastic solutions are assessed as a function of fragmentation rate. •The algorithms are applied to a multi-dimensional granulation model. -- Abstract: This paper introduces stochastic weighted particle algorithms for the solution of multi-compartment population balance equations. In particular, it presents a class of fragmentation weight transfer functions which are constructed such that the number of computational particles stays constant during fragmentation events. The weight transfer functions are constructed based on systems of weighted computational particles and each of it leads to a stochastic particle algorithm for the numerical treatment of population balance equations. Besides fragmentation, the algorithms also consider physical processes such as coagulation and the exchange of mass with the surroundings. The numerical properties of the algorithms are compared to the direct simulation algorithm and an existing method for the fragmentation of weighted particles. It is found that the new algorithms show better numerical performance over the two existing methods especially for systems with significant amount of large particles and high fragmentation rates.

Stochastic weighted particle methods for population balance equations with coagulation, fragmentation and spatial inhomogeneity

Energy Technology Data Exchange (ETDEWEB)

Lee, Kok Foong [Department of Chemical Engineering and Biotechnology, University of Cambridge, New Museums Site, Pembroke Street, Cambridge CB2 3RA (United Kingdom); Patterson, Robert I.A.; Wagner, Wolfgang [Weierstrass Institute for Applied Analysis and Stochastics, Mohrenstraße 39, 10117 Berlin (Germany); Kraft, Markus, E-mail: mk306@cam.ac.uk [Department of Chemical Engineering and Biotechnology, University of Cambridge, New Museums Site, Pembroke Street, Cambridge CB2 3RA (United Kingdom); School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore, 637459 (Singapore)

2015-12-15

Graphical abstract: -- Highlights: •Problems concerning multi-compartment population balance equations are studied. •A class of fragmentation weight transfer functions is presented. •Three stochastic weighted algorithms are compared against the direct simulation algorithm. •The numerical errors of the stochastic solutions are assessed as a function of fragmentation rate. •The algorithms are applied to a multi-dimensional granulation model. -- Abstract: This paper introduces stochastic weighted particle algorithms for the solution of multi-compartment population balance equations. In particular, it presents a class of fragmentation weight transfer functions which are constructed such that the number of computational particles stays constant during fragmentation events. The weight transfer functions are constructed based on systems of weighted computational particles and each of it leads to a stochastic particle algorithm for the numerical treatment of population balance equations. Besides fragmentation, the algorithms also consider physical processes such as coagulation and the exchange of mass with the surroundings. The numerical properties of the algorithms are compared to the direct simulation algorithm and an existing method for the fragmentation of weighted particles. It is found that the new algorithms show better numerical performance over the two existing methods especially for systems with significant amount of large particles and high fragmentation rates.

Mathematical processing of experimental data on neutron yield from separate fission fragments

International Nuclear Information System (INIS)

Basova, B.G.; Rabinovich, A.D.; Ryazanov, D.K.

1975-01-01

The algorithm is described for processing the multi-dimensional experiments on measurements of prompt emission of neutrons from separate fission fragments. While processing the data the effect of a number of experimental corrections is correctly taken into account; random coincidence background, neutron spectrum, neutron detector efficiency, instrument angular resolution. On the basis of the described algorithm a program for BESM-4 computer is realized and the treatment of experimental data is performed according to the spontaneous fission of 252 Cf

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

International Nuclear Information System (INIS)

Ding, C; Hrycushko, B; Jiang, S; Meyer, J; Timmerman, R

2014-01-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm 3 ) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan, the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment

Analysis of fission-fragment mass distribution within the quantum-mechanical fragmentation theory

Energy Technology Data Exchange (ETDEWEB)

Singh, Pardeep; Kaur, Harjeet [Guru Nanak Dev University, Department of Physics, Amritsar (India)

2016-11-15

The fission-fragment mass distribution is analysed for the {sup 208}Pb({sup 18}O, f) reaction within the quantum-mechanical fragmentation theory (QMFT). The reaction potential has been calculated by taking the binding energies, Coulomb potential and proximity potential of all possible decay channels and a stationary Schroedinger equation has been solved numerically to calculate the fission-fragment yield. The overall results for mass distribution are compared with those obtained in experiment. Fine structure dips in yield, corresponding to fragment shell closures at Z = 50 and N=82, which are observed by Bogachev et al., are reproduced successfully in the present calculations. These calculations will help to estimate the formation probabilities of fission fragments and to understand many related phenomena occurring in the fission process. (orig.)

Artificial ground motion compatible with specified peak ground displacement and target multi-damping response spectra

International Nuclear Information System (INIS)

Zhang Yushan; Zhao Fengxin

2010-01-01

With respect to the design ground motion of nuclear power plant (NPP), the Regular Guide 1.60 of the US not only defined the standard multi-damping response spectra, i.e. the RG1.60 spectra, but also definitely prescribed the peak ground displacement (PGD) value corresponding to the standard spectra. However, in the engineering practice of generating multi-damping-spectra-compatible artificial ground motion for the seismic design of NPP, the PGD value had been neglected. Addressing this issue, this paper proposed a synthesizing method which generates the artificial ground motion compatible with not only the target multi-damping response spectra but also the specified PGD value. Firstly, by the transfer formula between the power spectrum and the response spectrum, an initial uniformly modulated acceleration time history is synthesized by multiplying the stationary Gaussian process with the prescribed intensity envelope to simulate the amplitude-non-stationarity of earthquake ground motion. And then by superimposing a series of narrow-band time histories in the time domain, the initial time history is modified in the iterative manner to match the target PGD as well as the target multi-damping spectra with the pre-specified matching precisions. Numerical examples are provided to demonstrate the matching precisions of the proposed method to the target values.

Multi-agent Negotiation Mechanisms for Statistical Target Classification in Wireless Multimedia Sensor Networks

Science.gov (United States)

Wang, Xue; Bi, Dao-wei; Ding, Liang; Wang, Sheng

2007-01-01

The recent availability of low cost and miniaturized hardware has allowed wireless sensor networks (WSNs) to retrieve audio and video data in real world applications, which has fostered the development of wireless multimedia sensor networks (WMSNs). Resource constraints and challenging multimedia data volume make development of efficient algorithms to perform in-network processing of multimedia contents imperative. This paper proposes solving problems in the domain of WMSNs from the perspective of multi-agent systems. The multi-agent framework enables flexible network configuration and efficient collaborative in-network processing. The focus is placed on target classification in WMSNs where audio information is retrieved by microphones. To deal with the uncertainties related to audio information retrieval, the statistical approaches of power spectral density estimates, principal component analysis and Gaussian process classification are employed. A multi-agent negotiation mechanism is specially developed to efficiently utilize limited resources and simultaneously enhance classification accuracy and reliability. The negotiation is composed of two phases, where an auction based approach is first exploited to allocate the classification task among the agents and then individual agent decisions are combined by the committee decision mechanism. Simulation experiments with real world data are conducted and the results show that the proposed statistical approaches and negotiation mechanism not only reduce memory and computation requirements in WMSNs but also significantly enhance classification accuracy and reliability. PMID:28903223

A high-power target experiment

CERN Document Server

Kirk, H G; Ludewig, H; Palmer, Robert; Samulyak, V; Simos, N; Tsang, Thomas; Bradshaw, T W; Drumm, Paul V; Edgecock, T R; Ivanyushenkov, Yury; Bennett, Roger; Efthymiopoulos, Ilias; Fabich, Adrian; Haseroth, H; Haug, F; Lettry, Jacques; Hayato, Y; Yoshimura, Koji; Gabriel, Tony A; Graves, Van; Spampinato, P; Haines, John; McDonald, Kirk T

2005-01-01

We describe an experiment designed as a proof-of-principle test for a target system capable of converting a 4 MW proton beam into a high-intensity muon beam suitable for incorporation into either a neutrino factory complex or a muon collider. The target system is based on exposing a free mercury jet to an intense proton beam in the presence of a high strength solenoidal field.

Depth profiling of residual activity of ^{237}U fragments as a range verification technique for ^{238}U primary ion beam

Directory of Open Access Journals (Sweden)

I. Strašík

2012-07-01

Full Text Available Experimental and simulation data concerning fragmentation of ^{238}U ion beam in aluminum, copper, and stainless-steel targets with the initial energy 500 and 950  MeV/u are collected in the paper. A range-verification technique based on depth profiling of residual activity is presented. The irradiated targets were constructed in the stacked-foil geometry and analyzed using gamma-ray spectroscopy. One of the purposes of these experiments was depth profiling of residual activity of induced nuclides and projectile fragments. Among the projectile fragments, special attention is paid to the ^{237}U isotope that has a range very close to the range of the primary ^{238}U ions. Therefore, the depth profiling of the ^{237}U isotope can be utilized for experimental verification of the ^{238}U primary-beam range, which is demonstrated and discussed in the paper. The experimental data are compared with computer simulations by FLUKA, SRIM, and ATIMA, as well as with complementary experiments.

Accurate multi-robot targeting for keyhole neurosurgery based on external sensor monitoring.

Science.gov (United States)

Comparetti, Mirko Daniele; Vaccarella, Alberto; Dyagilev, Ilya; Shoham, Moshe; Ferrigno, Giancarlo; De Momi, Elena

2012-05-01

Robotics has recently been introduced in surgery to improve intervention accuracy, to reduce invasiveness and to allow new surgical procedures. In this framework, the ROBOCAST system is an optically surveyed multi-robot chain aimed at enhancing the accuracy of surgical probe insertion during keyhole neurosurgery procedures. The system encompasses three robots, connected as a multiple kinematic chain (serial and parallel), totalling 13 degrees of freedom, and it is used to automatically align the probe onto a desired planned trajectory. The probe is then inserted in the brain, towards the planned target, by means of a haptic interface. This paper presents a new iterative targeting approach to be used in surgical robotic navigation, where the multi-robot chain is used to align the surgical probe to the planned pose, and an external sensor is used to decrease the alignment errors. The iterative targeting was tested in an operating room environment using a skull phantom, and the targets were selected on magnetic resonance images. The proposed targeting procedure allows about 0.3 mm to be obtained as the residual median Euclidean distance between the planned and the desired targets, thus satisfying the surgical accuracy requirements (1 mm), due to the resolution of the diffused medical images. The performances proved to be independent of the robot optical sensor calibration accuracy.

Polarized internal targets for electronuclear experiments

International Nuclear Information System (INIS)

van den Brand, J.F.J.

1993-01-01

Polarized internal gas targets represent a unique opportunity for the measurement of spin observables in electro-nuclear physics. Two measurements will be discussed. First, spin observables have been measured in elastic and quasi-free scattering of 45, 200, 300, and 415 MeV polarized protons from a polarized 3 He internal gas target at the Indiana University Cyclotron Facility Cooler Ring. The data obtained constitute the first measurement of spin correlation parameters using a storage ring with polarized beam and polarized internal gas target. Second, a quasi-free (e,e'p) experiment using tensor polarized deuterium will be discussed. Here, the goal is the measurement of the S- and D-state parts of the proton spectral function by scattering 700 MeV electrons from an atomic beam source. Large acceptance detectors have been used in both experiments. The internal-target technique has broad applicability in nuclear and particle physics

Hitting emissions targets with (statistical) confidence in multi-instrument Emissions Trading Schemes

International Nuclear Information System (INIS)

Shipworth, David

2003-12-01

A means of assessing, monitoring and controlling aggregate emissions from multi-instrument Emissions Trading Schemes is proposed. The approach allows contributions from different instruments with different forms of emissions targets to be integrated. Where Emissions Trading Schemes are helping to meet specific national targets, the approach allows the entry requirements of new participants to be calculated and set at a level that will achieve these targets. The approach is multi-levelled, and may be extended downwards to support pooling of participants within instruments, or upwards to embed Emissions Trading Schemes within a wider suite of policies and measures with hard and soft targets. Aggregate emissions from each instrument are treated stochastically. Emissions from the scheme as a whole are then the joint probability distribution formed by integrating the emissions from its instruments. Because a Bayesian approach is adopted, qualitative and semi-qualitative data from expert opinion can be used where quantitative data is not currently available, or is incomplete. This approach helps government retain sufficient control over emissions trading scheme targets to allow them to meet their emissions reduction obligations, while minimising the need for retrospectively adjusting existing participants' conditions of entry. This maintains participant confidence, while providing the necessary policy levers for good governance

Mass spectrometry for fragment screening.

Science.gov (United States)

Chan, Daniel Shiu-Hin; Whitehouse, Andrew J; Coyne, Anthony G; Abell, Chris

2017-11-08

Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein-observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography. In this context, MS is a relatively underutilized technique in fragment screening for drug discovery. MS-based techniques have the advantage of high sensitivity, low sample consumption and being label-free. This review highlights recent examples of the emerging use of MS-based techniques in fragment screening. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Production of deuterons in hA collisions at high energies in the target fragmentation region

International Nuclear Information System (INIS)

Braun, M.A.; Vechernin, V.V.

1987-01-01

The production of relativistic deuterons in the target fragmentation region is studied. It is shown that for fast deuterons the role of the nuclear field is small and is not determined by the Butler-Pearson formulae. The main contribution comes from the direct coalescence into the deuteron of nucleons produced either at one point in the nucleus or at two different points. In the forward hemisphere for purely geometrical reasons the production at two points dominates, whereas in the backward hemisphere (the ''cumulative region'') the production at one point and at two different points may give contributions of the same order

PELE fragmentation dynamics

NARCIS (Netherlands)

Verreault, J.; Hinsberg, N.P. van; Abadjieva, E.

2013-01-01

An analytical model that describes the PELE fragmentation dynamics is presented and compared with experimental results from literature. The model accounts for strong shock effects and detailed interactions taking place between the filling – the inner core of the ammunition – and the target

Ranges of the fragments from thermal (slow) neutron fission of /sup 235/U in water

Energy Technology Data Exchange (ETDEWEB)

Gu, H; Chao, Z; Sheng, Z; Wang, L; Feng, X

1980-05-01

According to the principle of thick target, we used the aqueous solutions of uranyl chloride of various concentrations as thick targets and platinum plates of known surface area as absorbers immersed in the target solutions. The ranges of the U(n, f) fission fragments /sup 89/Sr, /sup 91/Y, /sup 140/Ba, /sup 141/Ce and /sup 144/Ce in the aqueous solutions of uranyl chloride of various concentrations were determined. In the concentration region of 0.16 U% - 6.2 U%, the uranium concentration had no significant effect on the measurement of the range. Therefore, the ranges of the fission fragments in diluted UO/sub 2/Cl/sub 2/ solutions are very close to those in pure water, and the mean value of the ranges in UO/sub 2/Cl/sub 2/ solutions of various concentrations was taken as the range in water. The experimental results of the ranges of these five fission fragments in water were: R/sub Sr-90/ = 2.39 +- 0.04 mgcm/sup -2/, R/sub Y-91/ = 2.35 +- 0.09 mgcm/sup -2/, R/sub Ba-140/ = 1.92 +- 0.07 mgcm/sup -2/, R/sub Ce-141/ = 1.91 +- 0.12 mgcm/sup -2/, R/sub Ce-144/ = 1.84 +- 0.10 mgcm/sup -2/. In order to estimate the effect of back scattering of fission fragments in platinum plate, we did the experiments using stainless steel plate as absorber (the aqueous solutions of uranyl chloride as thick targets). The results were similar. Thus, the effect of back scattering was not significant. This work provides a convenient means for determining the ranges of the fission fragments in a liquid.

Multi-agent target tracking using particle filters enhanced with context data

CSIR Research Space (South Africa)

Claessens, R

2015-05-01

Full Text Available The proposed framework for Multi-Agent Target Tracking supports i) tracking of objects and ii) search and rescue based on the fusion of very heterogeneous data. The system is based on a novel approach to fusing sensory observations, intelligence...

A Bayesian solution to multi-target tracking problems with mixed labelling

NARCIS (Netherlands)

Aoki, E.H.; Boers, Y.; Svensson, Lennart; Mandal, Pranab K.; Bagchi, Arunabha

In Multi-Target Tracking (MTT), the problem of assigning labels to tracks (track labelling) is vastly covered in literature and has been previously formulated using Bayesian recursion. However, the existing literature lacks an appropriate measure of uncertainty related to the assigned labels which

Fragmentation and Multifragmentation of 10.6 A GeV Gold Nuclei

CERN Document Server

Adamovich, M I

1999-01-01

We present the results of a study performed on the interactions of 10.6A GeV gold nuclei in nuclear emulsions. In a minimum bias sample of 1311 interac- tions, 5260 helium nuclei and 2622 heavy fragments were observed as Au projec- tile fragments. The experimental data are analyzed with particular emphasis of target separation interactions in emulsions and study of criticalexponents. Multiplicity distributions of the fast-moving projectile fragments are inves- tigated. Charged fragment moments, conditional moments as well as two and three -body asymmetries of the fast moving projectile particles are determined in terms of the total charge remaining bound in the multiply charged projectile fragments. Some differences in the average yields of helium nuclei and heavier fragments are observed, which may be attributed to a target effect. However, two and three-body asymmetries and conditional moments indicate that the breakup mechanism of the projectile seems to be independent of target mass. We looked for evidenc...

TimeLapseAnalyzer: Multi-target analysis for live-cell imaging and time-lapse microscopy

DEFF Research Database (Denmark)

Huth, Johannes; Buchholz, Malte; Kraus, Johann M.

2011-01-01

The direct observation of cells over time using time-lapse microscopy can provide deep insights into many important biological processes. Reliable analyses of motility, proliferation, invasive potential or mortality of cells are essential to many studies involving live cell imaging and can aid in...... counting and tube formation analysis in high throughput screening of live-cell experiments. TimeLapseAnalyzer is freely available (MATLAB, Open Source) at http://www.informatik.uniulm. de/ni/mitarbeiter/HKestler/tla......., we developed TimeLapseAnalyzer. Apart from general purpose image enhancements and segmentation procedures, this extensible, self-contained, modular cross-platform package provides dedicated modalities for fast and reliable analysis of multi-target cell tracking, scratch wound healing analysis, cell...

In vivo tumor targeting and imaging with engineered trivalent antibody fragments containing collagen-derived sequences.

Directory of Open Access Journals (Sweden)

Angel M Cuesta

Full Text Available There is an urgent need to develop new and effective agents for cancer targeting. In this work, a multivalent antibody is characterized in vivo in living animals. The antibody, termed "trimerbody", comprises a single-chain antibody (scFv fragment connected to the N-terminal trimerization subdomain of collagen XVIII NC1 by a flexible linker. As indicated by computer graphic modeling, the trimerbody has a tripod-shaped structure with three highly flexible scFv heads radially outward oriented. Trimerbodies are trimeric in solution and exhibited multivalent binding, which provides them with at least a 100-fold increase in functional affinity than the monovalent scFv. Our results also demonstrate the feasibility of producing functional bispecific trimerbodies, which concurrently bind two different ligands. A trimerbody specific for the carcinoembryonic antigen (CEA, a classic tumor-associated antigen, showed efficient tumor targeting after systemic administration in mice bearing CEA-positive tumors. Importantly, a trimerbody that recognizes an angiogenesis-associated laminin epitope, showed excellent tumor localization in several cancer types, including fibrosarcomas and carcinomas. These results illustrate the potential of this new antibody format for imaging and therapeutic applications, and suggest that some laminin epitopes might be universal targets for cancer targeting.

Free-time and fixed end-point multi-target optimal control theory: Application to quantum computing

International Nuclear Information System (INIS)

Mishima, K.; Yamashita, K.

2011-01-01

Graphical abstract: The two-state Deutsch-Jozsa algortihm used to demonstrate the utility of free-time and fixed-end point multi-target optimal control theory. Research highlights: → Free-time and fixed-end point multi-target optimal control theory (FRFP-MTOCT) was constructed. → The features of our theory include optimization of the external time-dependent perturbations with high transition probabilities, that of the temporal duration, the monotonic convergence, and the ability to optimize multiple-laser pulses simultaneously. → The advantage of the theory and a comparison with conventional fixed-time and fixed end-point multi-target optimal control theory (FIFP-MTOCT) are presented by comparing data calculated using the present theory with those published previously [K. Mishima, K. Yamashita, Chem. Phys. 361 (2009) 106]. → The qubit system of our interest consists of two polar NaCl molecules coupled by dipole-dipole interaction. → The calculation examples show that our theory is useful for minor adjustment of the external fields. - Abstract: An extension of free-time and fixed end-point optimal control theory (FRFP-OCT) to monotonically convergent free-time and fixed end-point multi-target optimal control theory (FRFP-MTOCT) is presented. The features of our theory include optimization of the external time-dependent perturbations with high transition probabilities, that of the temporal duration, the monotonic convergence, and the ability to optimize multiple-laser pulses simultaneously. The advantage of the theory and a comparison with conventional fixed-time and fixed end-point multi-target optimal control theory (FIFP-MTOCT) are presented by comparing data calculated using the present theory with those published previously [K. Mishima, K. Yamashita, Chem. Phys. 361, (2009), 106]. The qubit system of our interest consists of two polar NaCl molecules coupled by dipole-dipole interaction. The calculation examples show that our theory is useful for minor

Preliminary performance and ICF target experiments with Nova

International Nuclear Information System (INIS)

Drake, R.P.

1985-11-01

In December 1984, the Nova facility fired all ten laser arms, converted the output 1.05 micron energy to 0.35 micron light, and focused the 0.35 micron light through a 4 mm pinhole in the ten-beam target chamber. Since that time, a two-beam target chamber has been added, the performance of the laser evaluated, and preparation has been made for target experiments. This paper summarizes the performance of Nova and describes progress and plans for target experiments

Modelling of the PELE fragmentation dynamics

Science.gov (United States)

Verreault, J.

2014-05-01

The Penetrator with Enhanced Lateral Effect (PELE) is a type of explosive-free projectile that undergoes radial fragmentation upon an impact with a target plate. This type of projectile is composed of a brittle cylindrical shell (the jacket) filled in its core with a material characterized with a large Poisson's ratio. Upon an impact with a target, the axial compression causes the filling to expand in the radial direction. However, due to the brittleness of the jacket material, very little radial deformation can occur which creates a radial stress between the two materials and a hoop stress in the jacket. Fragmentation of the jacket occurs if the hoop stress exceeds the material's ultimate stress. The PELE fragmentation dynamics is explored via Finite-Element Method (FEM) simulations using the Autodyn explicit dynamics hydrocode. The numerical results are compared with an analytical model based on wave interactions, as well as with the experimental investigation of Paulus and Schirm (1996). The comparison is based on the mechanical stress in the filling and the qualitative fragmentation of the jacket.

Modelling of the PELE fragmentation dynamics

International Nuclear Information System (INIS)

Verreault, J

2014-01-01

The Penetrator with Enhanced Lateral Effect (PELE) is a type of explosive-free projectile that undergoes radial fragmentation upon an impact with a target plate. This type of projectile is composed of a brittle cylindrical shell (the jacket) filled in its core with a material characterized with a large Poisson's ratio. Upon an impact with a target, the axial compression causes the filling to expand in the radial direction. However, due to the brittleness of the jacket material, very little radial deformation can occur which creates a radial stress between the two materials and a hoop stress in the jacket. Fragmentation of the jacket occurs if the hoop stress exceeds the material's ultimate stress. The PELE fragmentation dynamics is explored via Finite-Element Method (FEM) simulations using the Autodyn explicit dynamics hydrocode. The numerical results are compared with an analytical model based on wave interactions, as well as with the experimental investigation of Paulus and Schirm (1996). The comparison is based on the mechanical stress in the filling and the qualitative fragmentation of the jacket.

In vivo characterization of the novel CD44v6-targeting Fab fragment AbD15179 for molecular imaging of squamous cell carcinoma: a dual-isotope study

Science.gov (United States)

2014-01-01

Background Patients with squamous cell carcinoma in the head and neck region (HNSCC) offer a diagnostic challenge due to difficulties to detect small tumours and metastases. Imaging methods available are not sufficient, and radio-immunodiagnostics could increase specificity and sensitivity of diagnostics. The objective of this study was to evaluate, for the first time, the in vivo properties of the radiolabelled CD44v6-targeting fragment AbD15179 and to assess its utility as a targeting agent for radio-immunodiagnostics of CD44v6-expressing tumours. Methods The fully human CD44v6-targeting Fab fragment AbD15179 was labelled with 111In or 125I, as models for radionuclides suitable for imaging with SPECT or PET. Species specificity, antigen specificity and internalization properties were first assessed in vitro. In vivo specificity and biodistribution were then evaluated in tumour-bearing mice using a dual-tumour and dual-isotope setup. Results Both species-specific and antigen-specific binding of the conjugates were demonstrated in vitro, with no detectable internalization. The in vivo studies demonstrated specific tumour binding and favourable tumour targeting properties for both conjugates, albeit with higher tumour uptake, slower tumour dissociation, higher tumour-to-blood ratio and higher CD44v6 sensitivity for the 111In-labelled fragment. In contrast, the 125I-Fab demonstrated more favourable tumour-to-organ ratios for liver, spleen and kidneys. Conclusions We conclude that AbD15179 efficiently targets CD44v6-expressing squamous cell carcinoma xenografts, and particularly, the 111In-Fab displayed high and specific tumour uptake. CD44v6 emerges as a suitable target for radio-immunodiagnostics, and a fully human antibody fragment such as AbD15179 can enable further clinical imaging studies. PMID:24598405

Composite Liner, Multi-Megabar Shock Driver Development

International Nuclear Information System (INIS)

Cochrane, J.C. Jr.; Bartsch, R.R.; Clark, D.A.; Morgan, D.V.; Anderson, W.E.; Lee, H.; Bowers, R.L.; Atchison, W.L.; Oona, H.; Stokes, J.L.; Veeser, L.R.; Broste, W.B.

1998-01-01

The multi-megabar shock driver development is a series of experiments in support of the Los Alamos High Energy Density Physics Experimental Program. Its purpose is to develop techniques to impact a uniform, stable, composite liner upon a high Z target to produce a multi-megabar shock for EOS studies. To date, experiments have been done on the Pegasus II capacitor bank with a current of approximately12MA driving the impactor liner. The driving field is approximately200 T at the target radius of 1cm. Data will be presented on the impactor liner. The driving field is approximately200 T at the target radius of 1 cm. Data will be presented on the stability and uniformity of the impactor liner when it impacts the target cylinder. Three experiments have been done with emphasis on liner development. Shock pressures greater than a megabar have been done with emphasis on liner development. Shock pressures greater than a megabar have been produced with an Al target cylinder. A Pt target cylinder should produce shock pressures in th e 5-megabar range

Target fragmentation in pp, ep and γp collisions at high energies

International Nuclear Information System (INIS)

D'Alesio, U.; Pirner, H.J.

2000-01-01

We calculate target fragmentation in pp→nX and γp→nX reactions in the meson cloud picture of the nucleon. The pp→nX reaction is used to fix the pnπ + form factor for three different models. We take into account the possible destruction of the residual neutron by the projectile. Using the form factor from the hadronic reaction we calculate photoproduction and small x Bj electroproduction of forward neutrons at HERA. Here the anti qq dipoles in the photon can rescatter on the residual neutron. In photoproduction we observe slightly less absorption than in the hadronic reaction. For deep inelastic events (Q 2 >10 GeV 2 ) screening is weaker but still present at large Q 2 . The signature for this absorptive rescattering is a shift of the dσ/dE n distribution to higher neutron energies for photofragmentation. (orig.)

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

Science.gov (United States)

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.

Target fragmentation in proton-nucleus and 16O-nucleus reactions at 60 and 200 GeV/nucleon

International Nuclear Information System (INIS)

Schmidt, H.R.; Albrecht, R.; Claesson, G.; Bock, R.; Gutbrod, H.H.; Kolb, B.W.; Lund, I.; Siemiarczuk, T.; Awes, T.C.; Baktash, C.; Ferguson, R.L.; Lee, I.Y.; Obenshain, F.E.; Plasil, F.; Sorensen, S.P.; Young, G.R.; Beckmann, P.; Berger, F.; Dragon, L.; Glasow, R.; Kampert, K.H.; Loehner, H.; Peitzmann, T.; Purschke, M.; Santo, R.; Franz, A.; Kristiansson, P.; Poskanzer, A.M.; Ritter, H.G.; Garpman, S.; Gustafsson, H.A.; Oskarsson, A.; Otterlund, I.; Persson, S.; Stenlund, E.

1988-01-01

Target remnants with Z 16 O-nucleus reactions at 60 and 200 GeV/nucleon were measured in the angular range from 30 0 to 160 0 (-1.7 16 O-induced reactions (≅ 300 MeV/c) than in proton-induced reactions (≅ 130 MeV/c). The baryon rapidity distributions are roughly in agreement with one-fluid hydrodynamical calculations at 60 GeV/nucleon 16 O+Au but are in disagreement at 200 GeV/nucleon, indicating the higher degree of transparency at the higher bombarding energy. Both, the transverse momenta of target spectators and the entropy produced in the target fragmentation region are compared to those attained in head-on collisions of two heavy nuclei at Bevalac energies. They are found to be comparable or do even exceed the values for the participant matter at beam energies of about 1-2 GeV/nucleon. (orig.)

Target fragmentation in proton-nucleus and 16O-nucleus reactions at 60 and 200 GeV/nucleon

International Nuclear Information System (INIS)

Schmidt, H.R.; Albrecht, R.; Claesson, G.; Bock, R.; Gutbrod, H.H.; Kolb, B.W.; Lund, I.; Siemiarczuk, T.; Awes, T.C.; Baktash, C.; Ferguson, R.L.; Lee, I.Y.; Obenshain, F.E.; Plasil, F.; Sorensen, S.P.; Young, G.R.; Beckmann, P.; Berger, F.; Dragon, L.; Glasow, R.; Kampert, K.H.; Loehner, H.; Peitzmann, T.; Purschke, M.; Santo, R.; Franz, A.; Kristiansson, P.; Poskanzer, A.M.; Ritter, H.G.; Garpman, S.; Gustafsson, H.A.; Oskarsson, A.; Otterlund, I.; Persson, S.; Stenlund, E.

1988-01-01

Target remnants with Z 16 O-nucleus reactions at 60 and 200 GeV/nucleon were measured in the angular range from 30 0 to 160 0 (-1.7 16 O-induced reactions (= 300 MeV/c) than in proton-induced reactions (= 130 MeV/c). The baryon rapidity distributions are roughly in agreement with one-fluid hydrodynamical calculations at 60 GeV/nucleon 16 O+Au but are in disagreement at 200 GeV/nucleon, indicating the higher degree of transparency at the higher bombarding energy. Both, the transverse momenta of target spectators and the entropy produced in the target fragmentation region are compared to those attained in head-on collisions of two heavy nuclei at Bevalac energies. They are found to be comparable or do even exceed the values for the participant matter at beam energies of about 1-2 GeV/nucleon. (orig.)

Multi-UAV joint target recognizing based on binocular vision theory

Directory of Open Access Journals (Sweden)

Yuan Zhang

2017-01-01

Full Text Available Target recognizing of unmanned aerial vehicle (UAV based on image processing take the advantage of 2D information containing in the image for identifying the target. Compare to single UAV with electrical optical tracking system (EOTS, multi-UAV with EOTS is able to take a group of image focused on the suspected target from multiple view point. Benefit from matching each couple of image in this group, points set constituted by matched feature points implicates the depth of each point. Coordinate of target feature points could be computing from depth of feature points. This depth information makes up a cloud of points and reconstructed an exclusive 3D model to recognizing system. Considering the target recognizing do not require precise target model, the cloud of feature points was regrouped into n subsets and reconstructed to a semi-3D model. Casting these subsets in a Cartesian coordinate and applying these projections in convolutional neural networks (CNN respectively, the integrated output of networks is the improved result of recognizing.

Multi-Targeted Antithrombotic Therapy for Total Artificial Heart Device Patients.

Science.gov (United States)

Ramirez, Angeleah; Riley, Jeffrey B; Joyce, Lyle D

2016-03-01

To prevent thrombotic or bleeding events in patients receiving a total artificial heart (TAH), agents have been used to avoid adverse events. The purpose of this article is to outline the adoption and results of a multi-targeted antithrombotic clinical procedure guideline (CPG) for TAH patients. Based on literature review of TAH anticoagulation and multiple case series, a CPG was designed to prescribe the use of multiple pharmacological agents. Total blood loss, Thromboelastograph(®) (TEG), and platelet light-transmission aggregometry (LTA) measurements were conducted on 13 TAH patients during the first 2 weeks of support in our institution. Target values and actual medians for postimplant days 1, 3, 7, and 14 were calculated for kaolinheparinase TEG, kaolin TEG, LTA, and estimated blood loss. Protocol guidelines were followed and anticoagulation management reduced bleeding and prevented thrombus formation as well as thromboembolic events in TAH patients postimplantation. The patients in this study were susceptible to a variety of possible complications such as mechanical device issues, thrombotic events, infection, and bleeding. Among them all it was clear that patients were at most risk for bleeding, particularly on postoperative days 1 through 3. However, bleeding was reduced into postoperative days 3 and 7, indicating that acceptable hemostasis was achieved with the anticoagulation protocol. The multidisciplinary, multi-targeted anticoagulation clinical procedure guideline was successful to maintain adequate antithrombotic therapy for TAH patients.

String fragmentation; La fragmentation des cordes

Energy Technology Data Exchange (ETDEWEB)

Drescher, H.J.; Werner, K. [Laboratoire de Physique Subatomique et des Technologies Associees - SUBATECH, Centre National de la Recherche Scientifique, 44 - Nantes (France)

1997-10-01

The classical string model is used in VENUS as a fragmentation model. For the soft domain simple 2-parton strings were sufficient, whereas for higher energies up to LHC, the perturbative regime of the QCD gives additional soft gluons, which are mapped on the string as so called kinks, energy singularities between the leading partons. The kinky string model is chosen to handle fragmentation of these strings by application of the Lorentz invariant area law. The `kinky strings` model, corresponding to the perturbative gluons coming from pQCD, takes into consideration this effect by treating the partons and gluons on the same footing. The decay law is always the Artru-Menessier area law which is the most realistic since it is invariant to the Lorentz and gauge transformations. For low mass strings a manipulation of the rupture point is necessary if the string corresponds already to an elementary particle determined by the mass and the flavor content. By means of the fragmentation model it will be possible to simulate the data from future experiments at LHC and RHIC 3 refs.

Beam-target interaction for high-dose, multi-pulse radiography

International Nuclear Information System (INIS)

DeVolder, B.G.; Kwan, T.J.T.; Snell, C.M.; Kares, R.J.; McLenithan, K.D.

1996-01-01

The conversion of an intense relativistic electron beam into x-rays for radiographic imaging is achieved through the bremsstrahlung process of electrons in a tantalum or tungsten target of some optimal thickness. A high-dose radiographic source with small spot size is needed to achieve desirable resolution for thick objects. Consequently, an extremely high brightness electron beam is used and a significant amount of electron beam energy can be deposited in a small area of the target. The authors describe a computational methodology used to model the beam-target interaction and the evolution of the resultant plasma. Several codes, including particle-in-cell (PIC), Monte Carlo transport, and magnetohydrodynamic (MHD) codes, contribute to simulate different parts of the problem in a linked fashion. Issues addressed by the calculations include: the effects of the time dependence of the energy profile deposited in the target; the influence of the external magnetic field on plasma expansion; the influence of the expanding plasma on the guide magnetic field; radiation effects; and multi-dimensional effects

The ways and means of fragment-based drug design.

Science.gov (United States)

Doak, Bradley C; Norton, Raymond S; Scanlon, Martin J

2016-11-01

Fragment-based drug design (FBDD) has emerged as a mainstream approach for the rapid and efficient identification of building blocks that can be used to develop high-affinity ligands against protein targets. One of the strengths of FBDD is the relative ease and low cost of the primary screen to identify fragments that bind. However, the fragments that emerge from primary screens often have low affinities, with K D values in the high μM to mM range, and a significant challenge for FBDD is to develop the initial fragments into more potent ligands. Successful fragment elaboration often requires co-structures of the fragments bound to their target proteins, as well as a range of biophysical and biochemical assays to track potency and efficacy. These challenges have led to the development of specific chemical strategies for the elaboration of weakly-binding fragments into more potent "hits" and lead compounds. In this article we review different approaches that have been employed to meet these challenges and describe some of the strategies that have resulted in several fragment-derived compounds entering clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Fragmentation of CO2 into C+ + O+ + O, in collisions with protons

International Nuclear Information System (INIS)

Moretto-Capelle, P.

2000-01-01

The fragmentation of CO 2 has been investigated in 25 keV H + + CO 2 collisions using an electron-ion-ion triple coincidence technique. In this letter we focus on the three-body fragmentation into the C + + O + + O final state. A comparison between the measured correlation of C + ,O + and O momenta and simple kinematic models allows us to demonstrate that in the present case, a rather unexpected two-step process with formation of a CO 2+ ion as an intermediate state occurs. This result is at variance with the conclusions of other authors achieved in collisions of photons and electrons with the dioxide molecule. Kinetic energy release distributions in the two steps of the dissociation process are also deduced from experiment; the distributions found for the fragmentation of CO 2+ into C + + O + are found to be very similar to those measured by other authors in collisions of various particles (photons, multi-charged ions) with CO molecules at high enough collision energy. (author). Letter-to-the-editor

Confidence from uncertainty - A multi-target drug screening method from robust control theory

Directory of Open Access Journals (Sweden)

Petzold Linda R

2010-11-01

Full Text Available Abstract Background Robustness is a recognized feature of biological systems that evolved as a defence to environmental variability. Complex diseases such as diabetes, cancer, bacterial and viral infections, exploit the same mechanisms that allow for robust behaviour in healthy conditions to ensure their own continuance. Single drug therapies, while generally potent regulators of their specific protein/gene targets, often fail to counter the robustness of the disease in question. Multi-drug therapies offer a powerful means to restore disrupted biological networks, by targeting the subsystem of interest while preventing the diseased network from reconciling through available, redundant mechanisms. Modelling techniques are needed to manage the high number of combinatorial possibilities arising in multi-drug therapeutic design, and identify synergistic targets that are robust to system uncertainty. Results We present the application of a method from robust control theory, Structured Singular Value or μ- analysis, to identify highly effective multi-drug therapies by using robustness in the face of uncertainty as a new means of target discrimination. We illustrate the method by means of a case study of a negative feedback network motif subject to parametric uncertainty. Conclusions The paper contributes to the development of effective methods for drug screening in the context of network modelling affected by parametric uncertainty. The results have wide applicability for the analysis of different sources of uncertainty like noise experienced in the data, neglected dynamics, or intrinsic biological variability.

Bespoke Fragments

DEFF Research Database (Denmark)

Kruse Aagaard, Anders

2016-01-01

, investigating levels of control and uncertainty encountering with these. Through tangible experiments, the project discusses materiality and digitally controlled fabrications tools as direct expansions of the architect's digital drawing and workflow. The project sees this expansion as an opportunity to connect...... architectural designs, tectonics and aesthetics. In this Ph.D.-project a series a physical, but conceptual, experiment plays the central role in the knowledge production. The experiments result in materialised architectural fragments and tangible experiences. However, these creations also become the driving...

Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells.

Science.gov (United States)

Byrne, Susan M; Ortiz, Luis; Mali, Prashant; Aach, John; Church, George M

2015-02-18

Sequence-specific nucleases such as TALEN and the CRISPR/Cas9 system have so far been used to disrupt, correct or insert transgenes at precise locations in mammalian genomes. We demonstrate efficient 'knock-in' targeted replacement of multi-kilobase genes in human induced pluripotent stem cells (iPSC). Using a model system replacing endogenous human genes with their mouse counterpart, we performed a comprehensive study of targeting vector design parameters for homologous recombination. A 2.7 kilobase (kb) homozygous gene replacement was achieved in up to 11% of iPSC without selection. The optimal homology arm length was around 2 kb, with homology length being especially critical on the arm not adjacent to the cut site. Homologous sequence inside the cut sites was detrimental to targeting efficiency, consistent with a synthesis-dependent strand annealing (SDSA) mechanism. Using two nuclease sites, we observed a high degree of gene excisions and inversions, which sometimes occurred more frequently than indel mutations. While homozygous deletions of 86 kb were achieved with up to 8% frequency, deletion frequencies were not solely a function of nuclease activity and deletion size. Our results analyzing the optimal parameters for targeting vector design will inform future gene targeting efforts involving multi-kilobase gene segments, particularly in human iPSC. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Linear transform of the multi-target survival curve

Energy Technology Data Exchange (ETDEWEB)

Watson, J V [Cambridge Univ. (UK). Dept. of Clinical Oncology and Radiotherapeutics

1978-07-01

A completely linear transform of the multi-target survival curve is presented. This enables all data, including those on the shoulder region of the curve, to be analysed. The necessity to make a subjective assessment about which data points to exclude for conventional methods of analysis is, therefore, removed. The analysis has also been adapted to include a 'Pike-Alper' method of assessing dose modification factors. For the data cited this predicts compatibility with the hypothesis of a true oxygen 'dose-modification' whereas the conventional Pike-Alper analysis does not.

Multicharged Ion-induced simple molecule fragmentation dynamics; Dynamique de la fragmentation de molecules simples induite par impact d'ion multicharge

Energy Technology Data Exchange (ETDEWEB)

Tarisien, M

2003-10-01

The aim of this work is to study the dynamics of swift multicharged ion-induced fragmentation of diatomic (CO) and triatomic (CO{sub 2}) molecules. Performed at the GANIL facility, this study used the Recoil Ion Momentum Spectroscopy technique (RIMS), which consists of a time-of-flight mass spectrometer, coupled with a multi-hit capability position sensitive detector (delay line anode). The high-resolution measurement of the kinetic energy distribution released (KER) during the CO fragmentation points out the limitation of the Coulomb Explosion Model, revealing, for example, the di-cation CO{sub 2}{sup +} electronic state contribution in the case of C{sup +}/O{sup +} fragmentation pathway. Furthermore, the multi-ionization cross section dependence with the orientation of the internuclear axis of CO is compared with a geometrical model calculation. Finally, different behaviours are observed for the dissociation dynamics of a triatomic molecule (CO{sub 2}). While triple ionization leads mainly to a synchronous concerted fragmentation dynamics, a weak fraction of dissociating molecule follows a sequential dynamics involving CO{sub 2}{sup +} metastable states. In the case of double ionization, (CO{sub 2}){sup 2+} di-cation dissociation dynamics is asynchronously concerted and has been interpreted using a simple model involving an asymmetrical vibration of the molecule. (author)

Single-spin asymmetry in electro-production of π+ π- pairs from a transversely polarized proton target at the HERMES experiment

International Nuclear Information System (INIS)

Lu, Xiao-Rui

2008-09-01

In this thesis, the measurement of an azimuthal amplitude of the asymmetry in the lepto-production of π + π - pairs at the HERMES experiment is reported. The experiment was carried out at DESY in Germany, utilizing the longitudinally polarized 27.6 GeV electron/positron beam of the HERA storage ring in combination with a longitudinally or transversely polarized gaseous target internal to the beam pipe. For the present measurement, the transversely polarized proton target was used and the beam polarization was averaged out in order to measure the asymmetry A UT . A Ring Imaging Cerenkov (RICH) detector allows the precise identification of pions, kaons and protons over essentially the entire momentum range of the experiment. The asymmetry A UT for π + π - pair production was measured for the first time in the world by HERMES. The amplitudes are extracted as functions of different kinematic variables, which can facilitate the comparison with the theoretical models and the extraction of transversity with combination of the measurement of the dihadron fragmentation function. (orig.)

TargetCrys: protein crystallization prediction by fusing multi-view features with two-layered SVM.

Science.gov (United States)

Hu, Jun; Han, Ke; Li, Yang; Yang, Jing-Yu; Shen, Hong-Bin; Yu, Dong-Jun

2016-11-01

The accurate prediction of whether a protein will crystallize plays a crucial role in improving the success rate of protein crystallization projects. A common critical problem in the development of machine-learning-based protein crystallization predictors is how to effectively utilize protein features extracted from different views. In this study, we aimed to improve the efficiency of fusing multi-view protein features by proposing a new two-layered SVM (2L-SVM) which switches the feature-level fusion problem to a decision-level fusion problem: the SVMs in the 1st layer of the 2L-SVM are trained on each of the multi-view feature sets; then, the outputs of the 1st layer SVMs, which are the "intermediate" decisions made based on the respective feature sets, are further ensembled by a 2nd layer SVM. Based on the proposed 2L-SVM, we implemented a sequence-based protein crystallization predictor called TargetCrys. Experimental results on several benchmark datasets demonstrated the efficacy of the proposed 2L-SVM for fusing multi-view features. We also compared TargetCrys with existing sequence-based protein crystallization predictors and demonstrated that the proposed TargetCrys outperformed most of the existing predictors and is competitive with the state-of-the-art predictors. The TargetCrys webserver and datasets used in this study are freely available for academic use at: http://csbio.njust.edu.cn/bioinf/TargetCrys .

Ion induced fragmentation of biomolecular systems at low collision energies

International Nuclear Information System (INIS)

Bernigaud, V; Adoui, L; Chesnel, J Y; Rangama, J; Huber, B A; Manil, B; Alvarado, F; Bari, S; Hoekstra, R; Postma, J; Schlathoelter, T

2009-01-01

In this paper, we present results of different collision experiments between multiply charged ions at low collision energies (in the keV-region) and biomolecular systems. This kind of interaction allows to remove electrons form the biomolecule without transferring a large amount of vibrational excitation energy. Nevertheless, following the ionization of the target, fragmentation of biomolecular species may occur. It is the main objective of this work to study the physical processes involved in the dissociation of highly electronically excited systems. In order to elucidate the intrinsic properties of certain biomolecules (porphyrins and amino acids) we have performed experiments in the gas phase with isolated systems. The obtained results demonstrate the high stability of porphyrins after electron removal. Furthermore, a dependence of the fragmentation pattern produced by multiply charged ions on the isomeric structure of the alanine molecule has been shown. By considering the presence of other surrounding biomolecules (clusters of nucleobases), a strong influence of the environment of the biomolecule on the fragmentation channels and their modification, has been clearly proven. This result is explained, in the thymine and uracil case, by the formation of hydrogen bonds between O and H atoms, which is known to favor planar cluster geometries.

Fractal statistics of brittle fragmentation

Directory of Open Access Journals (Sweden)

M. Davydova

2013-04-01

Full Text Available The study of fragmentation statistics of brittle materials that includes four types of experiments is presented. Data processing of the fragmentation of glass plates under quasi-static loading and the fragmentation of quartz cylindrical rods under dynamic loading shows that the size distribution of fragments (spatial quantity is fractal and can be described by a power law. The original experimental technique allows us to measure, apart from the spatial quantity, the temporal quantity - the size of time interval between the impulses of the light reflected from the newly created surfaces. The analysis of distributions of spatial (fragment size and temporal (time interval quantities provides evidence of obeying scaling laws, which suggests the possibility of self-organized criticality in fragmentation.

Target fragmentation in proton-nucleus and /sup 16/O-nucleus reactions at 60 and 200 GeVnucleon

Energy Technology Data Exchange (ETDEWEB)

Schmidt, H R; Albrecht, R; Awes, T C; Baktash, C; Beckmann, P; Claesson, G; Berger, F; Bock, R; Dragon, L; Ferguson, R L; Franz, A; Garpman, S; Glasow, R; Gustafsson, H A; Gutbrod, H H; Kampert, K H; Kolb, B W; Kristiansson, P; Lee, I Y; Loehner, H; Lund, I; Obenshain, F E; Oskarsson, A; Otterlund, I; Peitzmann, T; Persson, S; Plasil, F; Poskanzer, A M; Purschke, M; Ritter, H G; Santo, R; Siemiarczuk, T; Sorensen, S P; Stenlund, E; Young, G R

1987-01-01

Target remnants with Z<3 from proton-nucleus and /sup 16/O-nulceus reactions at 60 and 200 GeVnucleon were measured in the angular range from 30)degree) to 160)degree) (-1.7<)eta)1.3) employing the Plastic Ball detector. The excitation energy of the target spectator matter in central oxygen-induced collisions is found to be high enough to allow for complete disintegration of the target nucelus into fragments with Z<3. The average longtitudinal momentum transfer per proton to the target in central collisions is considerably higher in the case of /sup 16/O-induced reactions (approx.300 MeVc) than in proton-induced reactions (approx.130 MeVc). The baryon rapidity distributions are roughly in agreement with one-fluid hydrodynamical calcualtions at 60 GeVnucleon /sup 16/O)plus)Au but are in disagreement at 200 GeVnucleon, indicating the higher degree of transparency at the higher bombarding energy. Both, the transverse moments of target spectators and the entropy produced in the target gfragmentation region are compared to those attained in head-on collisions of two heavy nuclei at Bevalac energies. They are found to be comparable or do even exceed the values for the participant matter at beam energies of about 1-2 GeVnucleon. 18 refs., 112 figs

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

Science.gov (United States)

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.

Science.gov (United States)

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 .

Emission of fragments in heavy ion-collisions at Fermi energy

International Nuclear Information System (INIS)

Normand, J.

2001-10-01

The study of reaction mechanisms in Fermi energy domain has shown the dominant binary character of the process. The two heavy sources produced after the first stage of the interaction (the quasi-projectile QP and the quasi-target QT) can experience various decay modes from evaporation to multifragmentation. However, the presence of light fragments at mid rapidity cannot be explained by the standard decay of the QP and the QT. To understand the mechanisms producing such a contribution, the break-up of the QP has been studied on the following systems: Xe+Sn from 25 to 50 MeV/A, Ta+Au and Ta+U at 33, 39.6 MeV/A and U+U at 24 MeV/A. The experiment has been performed at GANIL with the INDRA multidetector. The particular behaviour of the heaviest fragment and the correlation between the charge and the velocity of the fragments suggest a shape deformation followed by the rupture of a neck formed in between the two partners of the collision. The heaviest fragment could be the reminiscence of the projectile. A method based on the angular distribution of the heaviest fragment has allowed to separate the statistical break-up of the QP and the non equilibrated break-up. The statistical break-up ranges from 30 % to 75 % of the break-ups. The comparison of the statistical component with a statistical model gives information about the charge, the angular momentum and the temperature of the QP. The comparison of the non equilibrated component with dynamical models could give information about the parameters of the nuclear interaction in medium. (author)

Fast reconstruction of multi-strange hyperons in the CBM experiment

Energy Technology Data Exchange (ETDEWEB)

Vassiliev, Iouri [GSI, Helmholtzzentrum fuer Schwerionenforschung GmbH, Darmstadt (Germany); Collaboration: CBM-Collaboration

2015-07-01

The main goal of the CBM experiment is to study the behaviour of nuclear matter at very high baryonic density in which the transition to a deconfined and chirally restored phase is expected to happen. One of the promissing signatures of this new state is the enhanced production of multi-strange particles, therefore the reconstruction of multi-strange hyperons is essential for the understanding of the heavy ion collision dynamics. Another experimental challenge of the CBM experiment is online selection of open charm particles via the displaced vertex of the hadronic decay, Charmonium and low mass vector mesons in the environment of a heavy-ion collision. This task requires fast and efficient track reconstruction algorithms, primary vertex finder and particles finder. Results of feasibility studies of the multi-strange hyperons in the CBM experiment are presented.

Unusual behavior of projectile fragments formed in the bombardment of copper with relativistic Ar ions

International Nuclear Information System (INIS)

Dersch, G.; Beckmann, R.; Feige, G.

1985-01-01

The interaction properties of projectile fragments from the fragmentation of 0.9 GeV/nucleon and 1.8 GeV/nucleon 40 Ar with Cu have been studied using radioactivation techniques. In this experiment, two identical copper blocks, 1 cm thick and 8 cm in diameter, are irradiated by relativistic projectiles in different configurations. In configuration 0, the blocks are touching while in configuration 10 or 20, the blocks are separated by 10 or 20 cm of air, respectively. It is assumed that when the relativistic projectiles interact with the first block of each pair, projectile fragments are created which interact with other nuclei in the first and second blocks. What is measured is the ratio of some target fragment activity, such as 24 Na or 28 Mg, produced in the second block relative to the first block, R

Emission of projectile helium fragments in 14N interactions at 2.1 GeV/nucleon

International Nuclear Information System (INIS)

Bhanja, R.; Devi, N.A.L.; Joseph, R.R.; Ojha, I.D.; Shyam, M.; Tuli, S.K.

1983-01-01

An analysis of projectile helium fragments has been performed from the point of view of testing the factorization and limiting fragmentation hypothesis. An event-by-event examination of 923 interactions of 14 N in emulsion at 2.1 GeV per nucleon has been made for target identification. Events with projectile fragments have been divided into various reaction channels according to the multiplicity of He nuclei. The multiplicity distribution, angular structure and other properties of the projectile He fragments have been investigated to see the dependence on different targets and target excitation. The properties of He fragments emitted from the projectile have been found to remain independent of target in peripheral collision processes. The target and projectile breakup properties have been analysed in terms of the collision geometry. Gaussian distributions have been fitted to the projected angular distribution data for He fragments at various intervals of impact parameter and in different reaction channels. The properties of emitted He nuclei exhibit characteristic features of factorization and limiting fragmentation. (orig.)

Complete fabrication of target experimental chamber and implement initial target diagnostics to be used for the first target experiments in NDCX-1

International Nuclear Information System (INIS)

Bieniosek, F.M.; Bieniosek, F.M.; Dickinson, M.R.; Henestroza, E.; Katayanagi, T.; Jung, J.Y.; Lee, C.W.; Leitner, M.; Ni, P.; Roy, P.; Seidl, P.; Waldron, W.; Welch, D.

2008-01-01

The Heavy Ion Fusion Science Virtual National Laboratory (HIFS-VNL) has completed the fabrication of a new experimental target chamber facility for future Warm Dense Matter (WDM) experiments, and implemented initial target diagnostics to be used for the first target experiments in NDCX-1. The target chamber has been installed on the NDCX-I beamline. This achievement provides to the HIFS-VNL unique and state-of-the-art experimental capabilities in preparation for the planned target heating experiments using intense heavy ion beams

Emission of fragments in heavy ion-collisions at Fermi energy; Modes de production des fragments dans les collisions d'ions lourds aux energies intermediaires

Energy Technology Data Exchange (ETDEWEB)

Normand, J

2001-10-01

The study of reaction mechanisms in Fermi energy domain has shown the dominant binary character of the process. The two heavy sources produced after the first stage of the interaction (the quasi-projectile QP and the quasi-target QT) can experience various decay modes from evaporation to multifragmentation. However, the presence of light fragments at mid rapidity cannot be explained by the standard decay of the QP and the QT. To understand the mechanisms producing such a contribution, the break-up of the QP has been studied on the following systems: Xe+Sn from 25 to 50 MeV/A, Ta+Au and Ta+U at 33, 39.6 MeV/A and U+U at 24 MeV/A. The experiment has been performed at GANIL with the INDRA multidetector. The particular behaviour of the heaviest fragment and the correlation between the charge and the velocity of the fragments suggest a shape deformation followed by the rupture of a neck formed in between the two partners of the collision. The heaviest fragment could be the reminiscence of the projectile. A method based on the angular distribution of the heaviest fragment has allowed to separate the statistical break-up of the QP and the non equilibrated break-up. The statistical break-up ranges from 30 % to 75 % of the break-ups. The comparison of the statistical component with a statistical model gives information about the charge, the angular momentum and the temperature of the QP. The comparison of the non equilibrated component with dynamical models could give information about the parameters of the nuclear interaction in medium. (author)

Forward-backward multiplicity correlations of target fragments in nucleus-emulsion collisions at a few hundred MeV/u

International Nuclear Information System (INIS)

Zhang Donghai; Chen Yanling; Wang Guorong; Li Wangdong; Wang Qing; Yao Jijie; Zhou Jianguo; Li Rong; Li Junsheng; Li Huiling

2015-01-01

The forward-backward multiplicity and correlations of a target evaporated fragment (black track particle) and target recoiled proton (grey track particle) emitted from 150 A MeV "4He, 290 A MeV "1"2C, 400 A MeV "1"2C, 400 A MeV "2"0Ne and 500 A MeV "5"6Fe induced different types of nuclear emulsion target interactions are investigated. It is found that the forward and backward averaged multiplicity of a grey, black and heavily ionized track particle increases with the increase of the target size. The averaged multiplicity of a forward black track particle, backward black track particle, and backward grey track particle do not depend on the projectile size and energy, but the averaged multiplicity of a forward grey track particle increases with an increase of projectile size and energy. The backward grey track particle multiplicity distribution follows an exponential decay law and the decay constant decreases with an increase of target size. The backward-forward multiplicity correlations follow linear law which is independent of the projectile size and energy, and the saturation effect is observed in some heavy target data sets. (authors)

On spallation and fragmentation of heavy ions at intermediate energies

International Nuclear Information System (INIS)

Musulmanbekov, G.; Al-Haidary, A.

2002-01-01

A new code for simulation of spallation and (multi)fragmentation of nuclei in proton and nucleus induced collisions at intermediate and high energies is developed. The code is a combination of modified intranuclear cascade model with traditional fission - evaporation part and multifragmentation part based on lattice representation of nuclear structure and percolation approach. The production of s-wave resonances and formation time concept included into standard intranuclear cascade code provides correct calculation of excitation energy of residues. This modified cascade code served as a bridge between low and high energy model descriptions of nucleus-nucleus collisions. A good agreement with experiments has been obtained for multiparticle production at intermediate and relatively high energies. Nuclear structure of colliding nuclei is represented as face centered cubic lattice. This representation, being isomorphic to the shell model of nuclear structure, allows to apply percolation approach for nuclear fragmentation. The offered percolation model includes both site and bond percolation. Broken sites represent holes left by nucleons knocked out at cascade state. Therefore, in the first cascade stage mutual rescattering of the colliding nuclei results in knocking some nucleons out of them. After this fast stage paltrily destruct and excited residues remain. On the second stage residual nuclei either evaporate nucleons and light nuclei up to alpha-particles or fragment into pieces with intermediate masses. The choice depends on residue's destruction degree. At low excitation energy and small destruction of the residue the evaporation and fission mechanisms are preferable. The more excitation energy and destruction the more probability of (multi)fragmentation process. Moreover, the more destruction degree of the residual the more the site percolation probability. It is concluded, that at low and intermediate excitation energies the fragmentation of nuclei is slow

Fragmentation of molten core material by sodium

International Nuclear Information System (INIS)

Chu, T.Y.

1982-01-01

A series of scoping experiments was performed to study the fragmentation of prototypic high temperature melts in sodium. The quantity of melt involved was at least one order of magnitude larger than previous experiments. Two modes of contact were used: melt streaming into sodium and sodium into melt. The average bulk fragment size distribution was found to be in the range of previous data and the average size distribution was found to be insensitive to mode of contact. SEM studies showed that the metal component typically fragmented in the molten phase while the oxide component fragmented in the solid phase. For UO 2 -ZrO 2 /stainless steel melts no sigificant spatial separation of the metal and oxide was observed. The fragment size distribution was stratified vertically in the debris bed in all cases. While the bulk fragment size showed generally consistent trends, the individual experiments were sufficiently different to cause different degrees of stratification in the debris bed. For the highly stratified beds the permeability can decrease by as much as a factor of 20 from the bottom to the top of the bed

On the configuration of an active target for a fixed-target B experiment at SSC energies

International Nuclear Information System (INIS)

Dukes, E.C.

1993-01-01

The optimal configuration of target and silicon microvertex detector for fixed-target B experiments has yet to be determined. For fixed-target charm experiments the usual setup consists of a series of inert target foils - typically a few millimeters thick and separated by a few centimeters - immediately followed by a silicon microvertex detector. Because of the larger boost at the SSC, the efficacy of using active target foils - tightly packed silicon microstrip detectors - has been considered by at least one group: the SFT collaboration. It is hoped that with an active target the tracks of charged B's themselves can be measured, improving charged B reconstruction efficiencies. The author examines two issues concerning silicon active targets for fixed-target experiments at the SSC: (1) the effect on the acceptance of the requirement that the B decay vertices occur outside of the target foils, and (2) the ability of an active target to directly track charged B's

Mechanisms Affecting Population Density in Fragmented Habitat

Directory of Open Access Journals (Sweden)

Lutz Tischendorf

2005-06-01

Full Text Available We conducted a factorial simulation experiment to analyze the relative importance of movement pattern, boundary-crossing probability, and mortality in habitat and matrix on population density, and its dependency on habitat fragmentation, as well as inter-patch distance. We also examined how the initial response of a species to a fragmentation event may affect our observations of population density in post-fragmentation experiments. We found that the boundary-crossing probability from habitat to matrix, which partly determines the emigration rate, is the most important determinant for population density within habitat patches. The probability of crossing a boundary from matrix to habitat had a weaker, but positive, effect on population density. Movement behavior in habitat had a stronger effect on population density than movement behavior in matrix. Habitat fragmentation and inter-patch distance may have a positive or negative effect on population density. The direction of both effects depends on two factors. First, when the boundary-crossing probability from habitat to matrix is high, population density may decline with increasing habitat fragmentation. Conversely, for species with a high matrix-to-habitat boundary-crossing probability, population density may increase with increasing habitat fragmentation. Second, the initial distribution of individuals across the landscape: we found that habitat fragmentation and inter-patch distance were positively correlated with population density when individuals were distributed across matrix and habitat at the beginning of our simulation experiments. The direction of these relationships changed to negative when individuals were initially distributed across habitat only. Our findings imply that the speed of the initial response of organisms to habitat fragmentation events may determine the direction of observed relationships between habitat fragmentation and population density. The time scale of post-fragmentation

Deexcitation processes in nuclear reactions: The study of hot hadronic matter

International Nuclear Information System (INIS)

Porile, N.T.

1993-01-01

The research program involved continuing analysis of Fermilab E-735, search for quark-gluon plasma (QGP) in bar p-p collisions; experiments on multi-fragmentation using reverse kinematics at the Bevalac; continuing study of target fragments produced in the interaction of copper with intermediate-energy heavy ions; and detector R ampersand D for the STAR detector at RHIC

Non-Destructive Multi-Analytical Approach to Study the Pigments of Wall Painting Fragments Reused in Mortars from the Archaeological Site of Pompeii (Italy

Directory of Open Access Journals (Sweden)

Domenico Miriello

2018-03-01

Full Text Available During the excavations carried out in Via di Mercurio (Regio VI, 9, 3 in Pompeii, in 2015, some red, green, black, and brown wall painting fragments were found in the preparatory layer of an ancient pavement which was probably built after the 62 AD earthquake. These fragments, derived from the rubble, were used as coarse aggregate to prepare the mortar for building the pavement. The wall painting fragments are exceptionally well preserved, which is an uncommon occurrence in the city of Pompeii. However, as they were enclosed in the mortar, the wall painting fragments were protected from the high temperatures (probably ranging between 180 °C and 380 °C produced by the eruption in 79 AD. The pigmented outer surface of each sample was analyzed using a non-destructive multi-analytical approach, by combining spectrophotometric colorimetry and portable X-ray fluorescence with micro-Raman spectroscopy. The compositional characterization of the samples revealed the presence of cuprorivaite, goethite, and celadonite in the green pigments; hematite in the red pigments; goethite in the brown pigment; and charcoal in the black pigment. These data probably provide us with the most “faithful picture” of the various red, green, black, and brown pigments used in Pompeii prior to the 79 AD eruption.

Interobserver variability of clinical target volume delineation in supra-diaphragmatic Hodgkin's disease. A multi-institutional experience

International Nuclear Information System (INIS)

Genovesi, Domenico; Cefaro, Giampiero Ausili; Vinciguerra, Annamaria

2011-01-01

To determine interobserver variability in clinical target volume (CTV) of supra-diaphragmatic Hodgkin's lymphoma. At the 2008 AIRO (Italian Society of Radiation Oncology) Meeting, the Radiation Oncology Department of Chieti proposed a multi-institutional contouring dummy-run of two cases of early stage supra-diaphragmatic Hodgkin's lymphoma after chemotherapy. Clinical history, diagnostics, and planning CT imaging were available on Chieti's radiotherapy website (www.radioterapia.unich.it). Participating centers were requested to delineate the CTV and submit it to the coordinating center. To quantify interobserver variability of CTV delineations, the total volume, craniocaudal, laterolateral, and anteroposterior diameters were calculated. A total of 18 institutions for case A and 15 institutions for case B submitted the targets. Case A presented significant variability in total volume (range: 74.1-1,157.1 cc), craniocaudal (range: 6.5-22.5 cm; median: 16.25 cm), anteroposterior (range: 5.04-14.82 cm; median: 10.28 cm), and laterolateral diameters (range: 8.23-22.88 cm; median: 15.5 cm). Mean CTV was 464.8 cc (standard deviation: 280.5 cc). Case B presented significant variability in total volume (range: 341.8-1,662 cc), cranio-caudal (range: 8.0-28.5 cm; median: 23 cm), anteroposterior (range: 7.9-1.8 cm; median: 11.1 cm), and laterolateral diameters (range: 12.9-24.0 cm; median: 18.8 cm). Mean CTV was 926.0 cc (standard deviation: 445.7 cc). This significant variability confirms the need to apply specific guidelines to improve contouring uniformity in Hodgkin's lymphoma. (orig.)

Overcoming the hurdles of multi-step targeting (MST) for effective radioimmunotherapy of solid tumors

International Nuclear Information System (INIS)

Larson, Steven M.; Cheung, Nai-Kong

2009-01-01

The 4 specific aims of this project are: (1) Optimization of MST to increase tumor uptake; (2) Antigen heterogeneity; (3) Characterization and reduction of renal uptake; and (4) Validation in vivo of optimized MST targeted therapy. This proposal focussed upon optimizing multistep immune targeting strategies for the treatment of cancer. Two multi-step targeting constructs were explored during this funding period: (1) anti-Tag-72 and (2) anti-GD2.

Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β

Science.gov (United States)

2016-01-01

Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3β, allow the systematic synthesis of related fragment analogues to explore fragment-level structure–activity relationship, and finally lead to the synthesis of a more potent compound. PMID:27660690

Fragmentation of a 500 MeV/nucleon 86Kr beam, investigated at the GSI projectile fragment separator

International Nuclear Information System (INIS)

Weber, M.; Donzaud, C.; Geissel, H.; Grewe, A.; Lewitowicz, M.; Magel, A.; Mueller, A.C.; Nickel, F.; Pfuetzner, M.; Piechaczek, A.; Pravikoff, M.; Roeckl, E.; Rykaczewski, K.; Saint-Laurent, M.G.; Schall, I.; Stephan, C.; Tassan-Got, L.; Voss, B.

1993-10-01

Production cross-sections and longitudinal momentum distributions have been investigated for reactions between a 500 MeV/nucleon 86 Kr beam and beryllium, copper and tantalum targets. Fragments in a wide A/Z range were studied at the projectile-fragment separator FRS at GSI. The experimental production cross-sections have been used for testing the predictions obtained from a semi-empirical parameterization, a statistical abrasion model and an intranuclear-cascade model. The present study allows to extrapolate the production cross-sections towards very neutron-rich isotopes such as the doubly magic nucleus 78 Ni. For fragments close to the projectile the measured longitudinal momentum distributions agrees qualitatively with a semi-empirical parameterization, which is based on the two-step picture of the fragmentation process. The momentum widths of lighter fragments, however, show deviations from this simple picture. (orig.)

The multiple roles of computational chemistry in fragment-based drug design

Science.gov (United States)

Law, Richard; Barker, Oliver; Barker, John J.; Hesterkamp, Thomas; Godemann, Robert; Andersen, Ole; Fryatt, Tara; Courtney, Steve; Hallett, Dave; Whittaker, Mark

2009-08-01

Fragment-based drug discovery (FBDD) represents a change in strategy from the screening of molecules with higher molecular weights and physical properties more akin to fully drug-like compounds, to the screening of smaller, less complex molecules. This is because it has been recognised that fragment hit molecules can be efficiently grown and optimised into leads, particularly after the binding mode to the target protein has been first determined by 3D structural elucidation, e.g. by NMR or X-ray crystallography. Several studies have shown that medicinal chemistry optimisation of an already drug-like hit or lead compound can result in a final compound with too high molecular weight and lipophilicity. The evolution of a lower molecular weight fragment hit therefore represents an attractive alternative approach to optimisation as it allows better control of compound properties. Computational chemistry can play an important role both prior to a fragment screen, in producing a target focussed fragment library, and post-screening in the evolution of a drug-like molecule from a fragment hit, both with and without the available fragment-target co-complex structure. We will review many of the current developments in the area and illustrate with some recent examples from successful FBDD discovery projects that we have conducted.

Multi-scale image segmentation method with visual saliency constraints and its application

Science.gov (United States)

Chen, Yan; Yu, Jie; Sun, Kaimin

2018-03-01

Object-based image analysis method has many advantages over pixel-based methods, so it is one of the current research hotspots. It is very important to get the image objects by multi-scale image segmentation in order to carry out object-based image analysis. The current popular image segmentation methods mainly share the bottom-up segmentation principle, which is simple to realize and the object boundaries obtained are accurate. However, the macro statistical characteristics of the image areas are difficult to be taken into account, and fragmented segmentation (or over-segmentation) results are difficult to avoid. In addition, when it comes to information extraction, target recognition and other applications, image targets are not equally important, i.e., some specific targets or target groups with particular features worth more attention than the others. To avoid the problem of over-segmentation and highlight the targets of interest, this paper proposes a multi-scale image segmentation method with visually saliency graph constraints. Visual saliency theory and the typical feature extraction method are adopted to obtain the visual saliency information, especially the macroscopic information to be analyzed. The visual saliency information is used as a distribution map of homogeneity weight, where each pixel is given a weight. This weight acts as one of the merging constraints in the multi- scale image segmentation. As a result, pixels that macroscopically belong to the same object but are locally different can be more likely assigned to one same object. In addition, due to the constraint of visual saliency model, the constraint ability over local-macroscopic characteristics can be well controlled during the segmentation process based on different objects. These controls will improve the completeness of visually saliency areas in the segmentation results while diluting the controlling effect for non- saliency background areas. Experiments show that this method works

Study of Particle Production and Nuclear Fragmentation in Relativistic Heavy-Ion Collisions in Nuclear Emulsions

CERN Multimedia

2002-01-01

% EMU11 \\\\ \\\\ We propose to use nuclear emulsions for the study of nuclear collisions of $^{207}$Pb, $^{197}$Au, and any other heavy-ion beams when they are available. We have, in the past, used $^{32}$S at 200A~GeV and $^{16}$O at 200A and 60A~GeV from CERN (Experiment EMU08) and at present the analysis is going on with $^{28}$Si beam from BNL at 14.5A~GeV. It will be important to compare the previous and the present investigations with the new $^{207}$Pb beam at 60-160A~GeV. We want to measure in nuclear emulsion, on an event by event basis, shower particle multiplicity, pseudorapidity density and density fluctuations of charged particles, charge multiplicity and angular distributions of projectile fragments, production and interaction cross-sections of heavily ionizing particles emitted from the target fragmentation. Special emphasis will be placed on the analysis of events produced in the central collisions which are selected on the basis of low energy fragments emitted from the target excitation. It woul...

What can a geography as dancing body? language-experience 'gesture-movement-affection' (fragments

Directory of Open Access Journals (Sweden)

Antonio Carlos Queiroz Filho

2016-12-01

Full Text Available Made of fragments, this paper proposes to think about relations and possible repercussions existing between language and experience from the perspective of some post-structuralist authors. I sought in reflection about body and dance a way to discuss this issue and at the same time, making a geography as something that produces in us affections. “What can a Geography as dancing body?” is beyond a question, an invitation, a proposition: a ballerina geography.

Multi-target camera tracking, hand-off and display LDRD 158819 final report

International Nuclear Information System (INIS)

Anderson, Robert J.

2014-01-01

Modern security control rooms gather video and sensor feeds from tens to hundreds of cameras. Advanced camera analytics can detect motion from individual video streams and convert unexpected motion into alarms, but the interpretation of these alarms depends heavily upon human operators. Unfortunately, these operators can be overwhelmed when a large number of events happen simultaneously, or lulled into complacency due to frequent false alarms. This LDRD project has focused on improving video surveillance-based security systems by changing the fundamental focus from the cameras to the targets being tracked. If properly integrated, more cameras shouldn't lead to more alarms, more monitors, more operators, and increased response latency but instead should lead to better information and more rapid response times. For the course of the LDRD we have been developing algorithms that take live video imagery from multiple video cameras, identifies individual moving targets from the background imagery, and then displays the results in a single 3D interactive video. In this document we summarize the work in developing this multi-camera, multi-target system, including lessons learned, tools developed, technologies explored, and a description of current capability.

Multi-target camera tracking, hand-off and display LDRD 158819 final report

Energy Technology Data Exchange (ETDEWEB)

Anderson, Robert J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2014-10-01

Modern security control rooms gather video and sensor feeds from tens to hundreds of cameras. Advanced camera analytics can detect motion from individual video streams and convert unexpected motion into alarms, but the interpretation of these alarms depends heavily upon human operators. Unfortunately, these operators can be overwhelmed when a large number of events happen simultaneously, or lulled into complacency due to frequent false alarms. This LDRD project has focused on improving video surveillance-based security systems by changing the fundamental focus from the cameras to the targets being tracked. If properly integrated, more cameras shouldn't lead to more alarms, more monitors, more operators, and increased response latency but instead should lead to better information and more rapid response times. For the course of the LDRD we have been developing algorithms that take live video imagery from multiple video cameras, identifies individual moving targets from the background imagery, and then displays the results in a single 3D interactive video. In this document we summarize the work in developing this multi-camera, multi-target system, including lessons learned, tools developed, technologies explored, and a description of current capability.

Multi-Target Camera Tracking, Hand-off and Display LDRD 158819 Final Report

Energy Technology Data Exchange (ETDEWEB)

Anderson, Robert J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Robotic and Security Systems Dept.

2014-10-01

Modern security control rooms gather video and sensor feeds from tens to hundreds of cameras. Advanced camera analytics can detect motion from individual video streams and convert unexpected motion into alarms, but the interpretation of these alarms depends heavily upon human operators. Unfortunately, these operators can be overwhelmed when a large number of events happen simultaneously, or lulled into complacency due to frequent false alarms. This LDRD project has focused on improving video surveillance-based security systems by changing the fundamental focus from the cameras to the targets being tracked. If properly integrated, more cameras shouldn’t lead to more alarms, more monitors, more operators, and increased response latency but instead should lead to better information and more rapid response times. For the course of the LDRD we have been developing algorithms that take live video imagery from multiple video cameras, identify individual moving targets from the background imagery, and then display the results in a single 3D interactive video. In this document we summarize the work in developing this multi-camera, multi-target system, including lessons learned, tools developed, technologies explored, and a description of current capability.

A Feasibility Experiment of a W-powder Target

CERN Multimedia

Charitonidis, N; Carreta, O; Densham, C; Davenne, T; Fabich, A; Loveridge, P; Rivkin, L

2014-01-01

The development of high‐power targets remains a key R&D activity for future facilities presently under study like the Neutrino Factory, Muon Collider or upgraded high‐ power super beams for long‐baseline neutrino experiments.  The choice of materials to sustain the beam power ranging up to MW levels is not trivial. Granular solid targets have been proposed and are being studied as a candidate for such high‐power target systems. In the recently commissioned HiRadMat facility at CERN, a feasibility  experiment of a tungsten powder target was performed. The experiment was designed to explore for first time the impact of a high‐power proton beam on a static W-powder target in a thimble configuration. The diagnostics of the experiment were based on remote high speed photography as well as on laser‐doppler vibration measurements of the target containers. Results from the experimental findings are presented ...

Beauty and charm production in fixed target experiments

International Nuclear Information System (INIS)

Kidonakis, Nikolaos; Vogt, Ramona

2004-01-01

We present calculations of NNLO threshold corrections for beauty and charm production in π - p and pp interactions at fixed-target experiments. Recent calculations for heavy quark hadroproduction have included next-to-next-to-leading-order (NNLO) soft-gluon corrections [1] to the double differential cross section from threshold resummation techniques [2]. These corrections are important for near-threshold beauty and charm production at fixed-target experiments, including HERA-B and some of the current and future heavy ion experiments

Fragment-Based Protein-Protein Interaction Antagonists of a Viral Dimeric Protease.

Science.gov (United States)

Gable, Jonathan E; Lee, Gregory M; Acker, Timothy M; Hulce, Kaitlin R; Gonzalez, Eric R; Schweigler, Patrick; Melkko, Samu; Farady, Christopher J; Craik, Charles S

2016-04-19

Fragment-based drug discovery has shown promise as an approach for challenging targets such as protein-protein interfaces. We developed and applied an activity-based fragment screen against dimeric Kaposi's sarcoma-associated herpesvirus protease (KSHV Pr) using an optimized fluorogenic substrate. Dose-response determination was performed as a confirmation screen, and NMR spectroscopy was used to map fragment inhibitor binding to KSHV Pr. Kinetic assays demonstrated that several initial hits also inhibit human cytomegalovirus protease (HCMV Pr). Binding of these hits to HCMV Pr was also confirmed by NMR spectroscopy. Despite the use of a target-agnostic fragment library, more than 80 % of confirmed hits disrupted dimerization and bound to a previously reported pocket at the dimer interface of KSHV Pr, not to the active site. One class of fragments, an aminothiazole scaffold, was further explored using commercially available analogues. These compounds demonstrated greater than 100-fold improvement of inhibition. This study illustrates the power of fragment-based screening for these challenging enzymatic targets and provides an example of the potential druggability of pockets at protein-protein interfaces. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Three-body fragmentation of methane dications produced by slow A r8 + -ion impact

Science.gov (United States)

Zhang, Y.; Jiang, T.; Wei, L.; Luo, D.; Wang, X.; Yu, W.; Hutton, R.; Zou, Y.; Wei, B.

2018-02-01

The three-body fragmentation dynamics of CH4 2 + dications induced by single-electron capture of slow (3-keV/u) A r8 + ions is investigated. The experiment is performed on a newly built, highly charged ion collision platform which consists of an electron cyclotron resonance ion source and a cold target recoil ion momentum spectroscopy (COLTRIMS) setup. Using the COLTRIMS methodology, the complete kinematical information is determined for two three-body breakup channels, CH4 2 +→H++CH2 ++H and CH4 2 +→H2 ++C H++H . Then analyzing the complete kinematics with the Dalitz plot, very different fragmentation mechanisms (e.g., sequential and/or concerted pathway) are clearly identified for the two channels. To confirm the existence of some possible fragmentation pathways, we also simulate corresponding Dalitz plots employing a simple classical mechanical model. For the H++CH2 ++H channel, the dependence of the fragmentation pathway on its kinetic energy release is studied, which reflects the different nature of the corresponding states of CH4 2 + dications. Furthermore, the kinetic energy ratio of two ionic fragments is analyzed to infer the three-body fragmentation mechanism of CH4 2 + dications.

MAFF–The Munich accelerator for fission fragments

Indian Academy of Sciences (India)

Research reactors; linear accelerator; beam transport; particle sources and targets; ion sources. Abstract. At the new high flux reactor FRM-II in Munich the accelerator MAFF (Munich accelerator for fission fragments) is under design. In the high neutron flux of 1014 n/cm2 s up to 1014 neutron-rich fission fragments per ...

Binding-site assessment by virtual fragment screening.

Directory of Open Access Journals (Sweden)

Niu Huang

2010-04-01

Full Text Available The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock approximately 11,000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors.

NMR screening in fragment-based drug design: a practical guide.

Science.gov (United States)

Kim, Hai-Young; Wyss, Daniel F

2015-01-01

Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

Fission fragment spins and spectroscopy

International Nuclear Information System (INIS)

Durell, J.L.

1988-01-01

Prompt γ-ray coincidence experiments have been carried out on γ-rays emitted from post-neutron emission fission fragments produced by the aup 19F + 197 Au and 18 O + 232 Th reactions. Decay schemes have been established for even-even nuclei ranging from 78 Se to 148 Nd. Many new states with spin up to ∼ 12h have been observed. Apart from providing a wealth of new information on the spectroscopy of neutron-rich nuclei, the data have been analyzed to determine the average spin of primary fission fragments as a function of fragment mass. The results suggest that the fragment spins are determined by the temperature and shape of the primary fragments at or near to scission

Scaling and critical behaviour in nuclear fragmentation

International Nuclear Information System (INIS)

Campi, X.

1990-09-01

These notes review recent results on nuclear fragmentation. An analysis of experimental data from exclusive experiments is made in the framework of modern theories of fragmentation of finite size objects. We discuss the existence of a critical regime of fragmentation and the relevance of scaling and finite size scaling

Repetition priming with Japanese Kana scripts in word-fragment completion.

Science.gov (United States)

Komatsu, S; Naito, M

1992-03-01

Manipulating two types of Japanese Kana script, Katakana and Hiragana, we examined the effects of a script change between study and test on later word-fragment completion. Throughout three experiments, materials were composed of foreign loan nouns normally written in Katakana, but not in Hiragana, according to approved usage in Japanese. Experiment 1 demonstrated the reliable size of cross-script priming between Katakana and Hiragana. In Experiment 2, cross-modal priming was substantial when modality of presentation was changed from auditory to visual. In Experiment 3, generating a target word from its definition induced priming comparable in size to that in the prior reading condition. These results have been confirmed in the Hiragana test, as well as in the Katakana test, thereby suggesting that some conceptual and modality-independent processes may also mediate repetition priming.

Fragment-based drug discovery and protein–protein interactions

Directory of Open Access Journals (Sweden)

Turnbull AP

2014-09-01

Full Text Available Andrew P Turnbull,1 Susan M Boyd,2 Björn Walse31CRT Discovery Laboratories, Department of Biological Sciences, Birkbeck, University of London, London, UK; 2IOTA Pharmaceuticals Ltd, Cambridge, UK; 3SARomics Biostructures AB, Lund, SwedenAbstract: Protein–protein interactions (PPIs are involved in many biological processes, with an estimated 400,000 PPIs within the human proteome. There is significant interest in exploiting the relatively unexplored potential of these interactions in drug discovery, driven by the need to find new therapeutic targets. Compared with classical drug discovery against targets with well-defined binding sites, developing small-molecule inhibitors against PPIs where the contact surfaces are frequently more extensive and comparatively flat, with most of the binding energy localized in “hot spots”, has proven far more challenging. However, despite the difficulties associated with targeting PPIs, important progress has been made in recent years with fragment-based drug discovery playing a pivotal role in improving their tractability. Computational and empirical approaches can be used to identify hot-spot regions and assess the druggability and ligandability of new targets, whilst fragment screening campaigns can detect low-affinity fragments that either directly or indirectly perturb the PPI. Once fragment hits have been identified and confirmed using biochemical and biophysical approaches, three-dimensional structural data derived from nuclear magnetic resonance or X-ray crystallography can be used to drive medicinal chemistry efforts towards the development of more potent inhibitors. A small-scale comparison presented in this review of “standard” fragments with those targeting PPIs has revealed that the latter tend to be larger, be more lipophilic, and contain more polar (acid/base functionality, whereas three-dimensional descriptor data indicate that there is little difference in their three

Using fragmentation trees and mass spectral trees for identifying unknown compounds in metabolomics.

Science.gov (United States)

Vaniya, Arpana; Fiehn, Oliver

2015-06-01

Identification of unknown metabolites is the bottleneck in advancing metabolomics, leaving interpretation of metabolomics results ambiguous. The chemical diversity of metabolism is vast, making structure identification arduous and time consuming. Currently, comprehensive analysis of mass spectra in metabolomics is limited to library matching, but tandem mass spectral libraries are small compared to the large number of compounds found in the biosphere, including xenobiotics. Resolving this bottleneck requires richer data acquisition and better computational tools. Multi-stage mass spectrometry (MSn) trees show promise to aid in this regard. Fragmentation trees explore the fragmentation process, generate fragmentation rules and aid in sub-structure identification, while mass spectral trees delineate the dependencies in multi-stage MS of collision-induced dissociations. This review covers advancements over the past 10 years as a tool for metabolite identification, including algorithms, software and databases used to build and to implement fragmentation trees and mass spectral annotations.

A Three-Dimensional Target Depth-Resolution Method with a Single-Vector Sensor.

Science.gov (United States)

Zhao, Anbang; Bi, Xuejie; Hui, Juan; Zeng, Caigao; Ma, Lin

2018-04-12

This paper mainly studies and verifies the target number category-resolution method in multi-target cases and the target depth-resolution method of aerial targets. Firstly, target depth resolution is performed by using the sign distribution of the reactive component of the vertical complex acoustic intensity; the target category and the number resolution in multi-target cases is realized with a combination of the bearing-time recording information; and the corresponding simulation verification is carried out. The algorithm proposed in this paper can distinguish between the single-target multi-line spectrum case and the multi-target multi-line spectrum case. This paper presents an improved azimuth-estimation method for multi-target cases, which makes the estimation results more accurate. Using the Monte Carlo simulation, the feasibility of the proposed target number and category-resolution algorithm in multi-target cases is verified. In addition, by studying the field characteristics of the aerial and surface targets, the simulation results verify that there is only amplitude difference between the aerial target field and the surface target field under the same environmental parameters, and an aerial target can be treated as a special case of a surface target; the aerial target category resolution can then be realized based on the sign distribution of the reactive component of the vertical acoustic intensity so as to realize three-dimensional target depth resolution. By processing data from a sea experiment, the feasibility of the proposed aerial target three-dimensional depth-resolution algorithm is verified.

Bespoke Fragments

DEFF Research Database (Denmark)

Kruse Aagaard, Anders

2017-01-01

The PhD project Bespoke Fragments is investigating the space emerging in the exploration of the relationship between digital drawing and fabrication, and the field of materials and their properties and capacities. Through a series of different experiments, the project situates itself in a shuttli...

Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries.

Science.gov (United States)

Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z

2012-02-01

Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. Copyright © 2011 Elsevier Inc. All rights reserved.

Study of Photoionization and Fragmentation on CHClF2 : Experiments and Calculations

International Nuclear Information System (INIS)

Sheng, L.; Yang, B.; Huang, C.; Qi, F.; Zhang, Y.; Wang, Z.; Zhou, S.

2004-01-01

Full text: The photoionization and fragmentation of CHClF 2 are studied with VUV radiation and photoionization mass spectroscopy at NSRL. Ionization potential of Parent molecule CHClF 2 , appearance energies of some fragment ions, and dissociative energy of some fragmentation process are obtained from photoionization efficiency spectroscopy. Dissociative photoionization channels for formation of some fragment ions are proposed on comparison of determined appearance energies and energies predicted with Gaussian-98 calculation

PLANS FOR WARM DENSE MATTER EXPERIMENTS AND IFE TARGET EXPERIMENTS ON NDCX-II

International Nuclear Information System (INIS)

Waldron, W.L.; Barnard, J.J.; Bieniosek, F.M.; Friedman, A.; Henestroza, E.; Leitner, M.; Logan, B.G.; Ni, P.A.; Roy, P.K.; Seidl, P.A.; Sharp, W.M.

2008-01-01

The Heavy Ion Fusion Science Virtual National Laboratory (HIFS-VNL) is currently developing design concepts for NDCX-II, the second phase of the Neutralized Drift Compression Experiment, which will use ion beams to explore Warm Dense Matter (WDM) and Inertial Fusion Energy (IFE) target hydrodynamics. The ion induction accelerator will consist of a new short pulse injector and induction cells from the decommissioned Advanced Test Accelerator (ATA) at Lawrence Livermore National Laboratory (LLNL). To fit within an existing building and to meet the energy and temporal requirements of various target experiments, an aggressive beam compression and acceleration schedule is planned. WDM physics and ion-driven direct drive hydrodynamics will initially be explored with 30 nC of lithium ions in experiments involving ion deposition, ablation, acceleration and stability of planar targets. Other ion sources which may deliver higher charge per bunch will be explored. A test stand has been built at Lawrence Berkeley National Laboratory (LBNL) to test refurbished ATA induction cells and pulsed power hardware for voltage holding and ability to produce various compression and acceleration waveforms. Another test stand is being used to develop and characterize lithium-doped aluminosilicate ion sources. The first experiments will include heating metallic targets to 10,000 K and hydrodynamics studies with cryogenic hydrogen targets

Pilot experiments with relativistic uranium projectile and fission fragments thermalized in a cryogenic gas-filled stopping cell

Energy Technology Data Exchange (ETDEWEB)

Reiter, Moritz Pascal

2015-07-01

High precision experiments and decay spectroscopy of exotic nuclei are of great interest for nuclear structure and nuclear astro-physics. They allow for studies of the nuclear structure far from stability, test of fundamental interactions and symmetries and give important input for the understanding of the nuclear synthesis in the universe. In the context of this work a second generation stopping cell for the low energy branch of the Super-FRS was commissioned at the FRS at GSI and significant improvements were made to the device. The prototype stopping cell is designed as a cryogenic stopping cell (CSC), featuring enhanced cleanliness and high area density. The CSC was brought into full operation and its performance characteristics were investigated including the maximal area density, extraction times, cleanliness and extraction efficiencies. In three commissioning experiments at the current GSI FRS facility in 2011, 2012 and 2014 up to 22 isotopes from 14 elements produced by in-flight projectile fragmentation and fission of {sup 238}U could be thermalized and extracted with high efficiency. For the first time projectile and fission fragmentation produced at 1000 MeV/u could be thermalized in a stopping cell and provided as a low-energy beam of high brilliance for high precision experiments. The technical improvements of the CSC, such as an improved RF carpet, new cryocooler-based cooling system, a monitoring system of the cleanliness and the high density operation, made it possible to thermalize heavy {sup 238}U projectile fragments with total efficiencies of about 20% in the 2014 experiment. In addition the improvements lead to an increase in the stability and reliability of the CSC and the performance of the CSC during online experiments at the FRS Ion Catcher showed that the utilized techniques are ready for the final CSC for the low-energy branch of the Super-FRS at FAIR. The CSC was operated with an area density of up to 6.3 mg/cm{sup 2} helium during

Pilot experiments with relativistic uranium projectile and fission fragments thermalized in a cryogenic gas-filled stopping cell

International Nuclear Information System (INIS)

Reiter, Moritz Pascal

2015-01-01

High precision experiments and decay spectroscopy of exotic nuclei are of great interest for nuclear structure and nuclear astro-physics. They allow for studies of the nuclear structure far from stability, test of fundamental interactions and symmetries and give important input for the understanding of the nuclear synthesis in the universe. In the context of this work a second generation stopping cell for the low energy branch of the Super-FRS was commissioned at the FRS at GSI and significant improvements were made to the device. The prototype stopping cell is designed as a cryogenic stopping cell (CSC), featuring enhanced cleanliness and high area density. The CSC was brought into full operation and its performance characteristics were investigated including the maximal area density, extraction times, cleanliness and extraction efficiencies. In three commissioning experiments at the current GSI FRS facility in 2011, 2012 and 2014 up to 22 isotopes from 14 elements produced by in-flight projectile fragmentation and fission of "2"3"8U could be thermalized and extracted with high efficiency. For the first time projectile and fission fragmentation produced at 1000 MeV/u could be thermalized in a stopping cell and provided as a low-energy beam of high brilliance for high precision experiments. The technical improvements of the CSC, such as an improved RF carpet, new cryocooler-based cooling system, a monitoring system of the cleanliness and the high density operation, made it possible to thermalize heavy "2"3"8U projectile fragments with total efficiencies of about 20% in the 2014 experiment. In addition the improvements lead to an increase in the stability and reliability of the CSC and the performance of the CSC during online experiments at the FRS Ion Catcher showed that the utilized techniques are ready for the final CSC for the low-energy branch of the Super-FRS at FAIR. The CSC was operated with an area density of up to 6.3 mg/cm"2 helium during online

The spectroscopy of fission fragments

International Nuclear Information System (INIS)

Phillips, W.R.

1998-01-01

High-resolution measurements on γ rays from fission fragments have provided a rich source of information, unobtainable at the moment in any other way, on the spectroscopy of neutron-rich nuclei. In recent years important data have been obtained on the yrast- and near yrast-structure of neutron-rich fission fragments. We discuss the scope of measurements which can be made on prompt gamma rays from secondary fission fragments, the techniques used in the experiments and some results recently obtained. (author)

Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem.

Science.gov (United States)

Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar

2016-12-13

Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design.

Thermal experiments in the ADS target model

International Nuclear Information System (INIS)

Efanov, A.D.; Orlov, Yu.I.; Sorokin, A.P.; Ivanov, E.F.; Bogoslovskaya, G.P.; Li, N.

2002-01-01

Experiments on the development of the target heat model project and method of investigation into heat exchange in target were conducted with the aim of analysis of thermomechanical and strength characteristics of device; experimental data on the temperature distribution in coolant and membrane were obtained. Obtained data demonstrate that the temperature heterogeneity of membrane and coolant are connected with the temperature distribution variability near the membrane. Peculiarities of the experiment are noted: maximal temperature of oscillations at high point of the membrane, and power bearing temperature oscillations in the range 0 - 1 Hz [ru

[Fragment-based drug discovery: concept and aim].

Science.gov (United States)

Tanaka, Daisuke

2010-03-01

Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to "undruggable targets" (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.

Fragmentation of small molecules induced by 46 keV/amu N+ and N2+ projectiles

International Nuclear Information System (INIS)

Kovacs, S.T.S.; Juhasz, Z.; Herczku, P.; Sulik, B.

2012-01-01

Complete text of publication follows. Collisional molecule fragmentation experiments has gain increasing attention in several research and applied fields. In order to understand the fundamental processes of molecule fragmentation one has to start with collisions of small few-atomic molecules. Moreover, fragments of small molecules such as water can cause damages of large molecules (DNA) very effectively in living tissues. In the last few years a new experimental setup was developed at Atomki. It was designed especially for molecule fragmentation experiments. Now the measurements using this system are running routinely. In 2012 the studied targets were water vapor, methane and nitrogen gases, injected into the collision area by an effusive molecular gas jet system. 650 keV N + and 1,3 MeV N 2 + ions were used as projectiles produced by the VdG-5 electrostatic accelerator. The velocity of the two types of projectiles was the same. Energy and angular distribution of the produced fragments was measured by an energy dispersive electrostatic spectrometer. For atomic ionization a symmetric, diatomic molecular projectile (e.g. N 2 + ) yields about twice more electrons compared to those of singly charged ion projectiles of the same atom (N + ) at the same velocity. In such cases the two atomic centers in the molecular ion can be considered as two individual atomic centers. For the fragmentation of molecular targets the picture is not so simple because in this case close collision of two extended systems is investigated. As figure 1 and 2 show, the measured yields for molecular projectile is not simply twice of the ones for atomic projectile. The shape of the energy spectra are different. The measured data are under evaluation. Acknowledgements. This work was supported by the Hungarian National Science Foundation OTKA (Grant: K73703) and by the TAMOP-4.2.2/B-10/1-2010-0024 project. The project is cofinanced by the European Union and the European Social Fund.

Design choices and issues in fixed-target B experiments

International Nuclear Information System (INIS)

Camilleri, L.

1993-01-01

The main priority of any experiment on B physics in the years to come will be an endeavour to observe CP violation in the B sector. Such measurements imply the following requirements of the experiment. Trigger: a muon trigger will be sensitive to J/ψ reactions and muon tags; an electron trigger will double the number of lepton events; in order to include kaon tags and self-tagging reactions, the experiment must not rely entirely on lepton triggers. Secondary Vertex triggers and hadron p T triggers should be included in order to have the maximum flexibility. Detector: vertex detector; particle identification; good momentum resolution; electromagnetic and hadronic calorimeters; muon detector. In addition the following issues have to be addressed: Collider or fixed-target mode? If fixed target, extracted beam or internal target? If internal target, gas jet or wire target? If a gas jet, hydrogen or a heavy gas? Beam pipe design. Silicon microvertex design and radiation damage. K s 0 decay path. Particle identification. Momentum resolution. Order of detectors. No single method stands out as the open-quotes obvious one.close quotes An extracted beam yields better vertex resolution and an internal target easier triggering. A flexible and diverse triggering scheme is of prime importance in order to be sensitive to as many reactions as possible, the experiment should not be limited to lepton triggers only. Proposed experiments (P867, HERA B) at existing machines will be invaluable for testing new devices and strategies for the LHC and SSC experiments

Velocity distribution of fragments of catastrophic impacts

Science.gov (United States)

Takagi, Yasuhiko; Kato, Manabu; Mizutani, Hitoshi

1992-01-01

Three dimensional velocities of fragments produced by laboratory impact experiments were measured for basalts and pyrophyllites. The velocity distribution of fragments obtained shows that the velocity range of the major fragments is rather narrow, at most within a factor of 3 and that no clear dependence of velocity on the fragment mass is observed. The NonDimensional Impact Stress (NDIS) defined by Mizutani et al. (1990) is found to be an appropriate scaling parameter to describe the overall fragment velocity as well as the antipodal velocity.

Fragmentation and nucleon structure in semi-inclusive deep-inelastic scattering at the HERMES experiment

Energy Technology Data Exchange (ETDEWEB)

Jossten, Sylvester Johannes

2013-10-15

Multiplicities for the semi-inclusive production of each charge state of {pi}{sup {+-}} and K{sup {+-}} mesons in deep-inelastic scattering are presented as a function of the kinematic quantities x, Q{sup 2}, z and P{sub h} {sub perpendicular} {sub to}. The multiplicities were extracted from data collected by the HERMES experiment at the HERA storage ring using 27.6 GeV electron and positron beams on a hydrogen or deuterium gas target. These results for identified hadrons constitute the most precise measurement to date, and will significantly enhance our understanding of the proton structure, as well as the fragmentation process in deep-inelastic scattering. Furthermore, the 3D binning at an unprecedented level of precision provides a handle to help disentangle the transverse momentum structure of both. The high level of precision coupled with an intermediate energy regime requires a careful study of the complex interaction between the experimental systematics, theoretical uncertainties, and the applicability of the factorization theorem within the standard framework of leading-twist collinear QCD. This is illustrated by the extraction of the valence quark ratio d{sub {nu}}/u{sub {nu}} at leading-order in {alpha}{sub s}. These results show a strong z-dependence below z {approx} 0.30, which could be interpreted as evidence for factorization breaking. This evidence weakens somewhat when isospin invariance of the fragmentation functions is assumed to be broken. Additionally, the multiplicities for the semi-inclusive production of {pi}{sup 0} mesons in deep-inelastic scattering are presented as a function of z. These multiplicities were extracted from the same data sample as used for the charged meson results. The neutral pion multiplicity is the same as the average charged pion multiplicity, up to z {approx} 0.70. This is consistent with isospin invariance below z {approx} 0.70. The results at high values of z show strong signs of isospin symmetry breaking.

Biological evaluation and molecular docking of Rhein as a multi-targeted radiotherapy sensitization agent of nasopharyngeal carcinoma

Science.gov (United States)

Su, Zhengying; Tian, Wei; Li, Jing; Wang, Chunmiao; Pan, Zhiyu; Li, Danrong; Hou, Huaxin

2017-11-01

Radiation resistance of nasopharyngeal carcinoma (NPC) is a joint effect caused by complex molecular mechanisms. The development of multi-target radiotherapy sensitization agents offered a promising method for the treatment of NPC. In this work, the probability of Rhein to be a multi-target radiotherapy sensitization agent was explored through computer aid virtual screening by inverse docking study. In order to validate the accuracy of the computational results, radiotherapy sensitization of Rhein to NPC cells and its effects on the expression of target proteins were evaluated separately by CCK8 assay and Western blotting analysis. Our result demonstrated that Rhein possessed strong binding affinity with RAC1 and HSP90. No cytotoxic concentration of Rhein had radiosensitization effect on nasopharyngeal carcinoma CNE1 cells. After treatment with Rhein and 2Gy radiation, the expression of RAC1 upregulated and the expression of HSP90 down-regulated in cells. Based on the above data, Rhein is likely to become an attractive lead compound for the future design of multi-target radiotherapy sensitization agents.

Fragment-based discovery of a potent NAMPT inhibitor.

Science.gov (United States)

Korepanova, Alla; Longenecker, Kenton L; Pratt, Steve D; Panchal, Sanjay C; Clark, Richard F; Lake, Marc; Gopalakrishnan, Sujatha M; Raich, Diana; Sun, Chaohong; Petros, Andrew M

2017-12-12

NAMPT expression is elevated in many cancers, making this protein a potential target for anticancer therapy. We have carried out both NMR based and TR-FRET based fragment screens against human NAMPT and identified six novel binders with a range of potencies. Co-crystal structures were obtained for two of the fragments bound to NAMPT while for the other four fragments force-field driven docking was employed to generate a bound pose. Based on structural insights arising from comparison of the bound fragment poses to that of bound FK866 we were able to synthetically elaborate one of the fragments into a potent NAMPT inhibitor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fragmentation and lateral scattering of 120 and 200 MeV/u {sup 4}He ions in water targets

Energy Technology Data Exchange (ETDEWEB)

Rovituso, Marta

2016-06-02

Along with an increased popularity of heavy ions in cancer therapy, {sup 4}He ions have regained the interest of the medical community as a compromise between protons and {sup 12}C ions. Although 2054 patients have been treated with {sup 4}He beams at Lawrence Berkeley Laboratory (LBL) (Berkeley CA, US) between 1975 and 1992, a comprehensive database of biological and physics measurements in the therapeutic energy range is still missing. One of the first steps necessary for introducing {sup 4}He ions in particle therapy, is the development of a dedicated treatment planning system, for which basic physics information such as the characterization of the beam lateral scattering and fragmentation cross sections describing the loss of primary particles and the build up of secondary fragments are required. Examination of data found in the literature reveals a gap in the therapeutic energy range. These measurements are essential for benchmarking not only the new model developed for the in-house treatment planning code TRiP98 (Treatment Planning for Particles), but also for already existing beam algorithms and for Monte Carlo codes like Geant4 and Fluka. The aim of this work is to provide fragmentation cross sections of {sup 4}He ions in the therapeutic energy range. The experimental data presented here were measured at Heidelberg Ion Beam Therapy Center (HIT) (Heidelberg, Germany) using 120 MeV/u and 200 MeV/u {sup 4}He beams. The attenuation of 200 MeV/u {sup 4}He beam in water was studied together with the build up of the secondary fragments produced by nuclear fragmentation processes. Target thicknesses between 1 and 25 cm H{sub 2}O were chosen to investigate nuclear fragmentation also beyond the maximum penetration depth of the {sup 4}He ions. The mixed radiation field produced by the interaction of 120 and 200 {sup 4}He ions with water targets (4.28 and 13.96 cm thick, respectively) has also been investigated in this work by measuring double differential cross

The spectroscopy of fission fragments

Energy Technology Data Exchange (ETDEWEB)

Phillips, W.R. [Department of Physics and Astronomy, University of Manchester, Manchester, M13 9PL (United Kingdom); Collaboration: La Direction des Sciences de la Matiere du CEA (FR); Le Fonds National de la Recherche Scientifique de Belgique (BE)

1998-12-31

High-resolution measurements on {gamma} rays from fission fragments have provided a rich source of information, unobtainable at the moment in any other way, on the spectroscopy of neutron-rich nuclei. In recent years important data have been obtained on the yrast- and near yrast-structure of neutron-rich fission fragments. We discuss the scope of measurements which can be made on prompt gamma rays from secondary fission fragments, the techniques used in the experiments and some results recently obtained. (author) 24 refs., 8 figs., 1 tab.

Single-spin asymmetry in electro-production of {pi}{sup +} {pi}{sup -} pairs from a transversely polarized proton target at the HERMES experiment

Energy Technology Data Exchange (ETDEWEB)

Lu, Xiao-Rui

2008-10-15

In this thesis, the measurement of an azimuthal amplitude of the asymmetry in the lepto-production of {pi}{sup +}{pi}{sup -} pairs at the HERMES experiment is reported. The experiment was carried out at DESY in Germany, utilizing the longitudinally polarized 27.6 GeV electron/positron beam of the HERA storage ring in combination with a longitudinally or transversely polarized gaseous target internal to the beam pipe. For the present measurement, the transversely polarized proton target was used and the beam polarization was averaged out in order to measure the asymmetry A{sub UT}. A Ring Imaging Cerenkov (RICH) detector allows the precise identification of pions, kaons and protons over essentially the entire momentum range of the experiment. The asymmetry A{sub UT} for {pi}{sup +}{pi}{sup -} pair production was measured for the first time in the world by HERMES. The amplitudes are extracted as functions of different kinematic variables, which can facilitate the comparison with the theoretical models and the extraction of transversity with combination of the measurement of the dihadron fragmentation function. (orig.)

Building a better fragment library for de novo protein structure prediction.

Directory of Open Access Journals (Sweden)

Saulo H P de Oliveira

Full Text Available Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10. We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. "Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources".

Building a Better Fragment Library for De Novo Protein Structure Prediction

Science.gov (United States)

de Oliveira, Saulo H. P.; Shi, Jiye; Deane, Charlotte M.

2015-01-01

Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10). We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. “Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources”. PMID:25901595

Human/murine chimeric 81C6 F(ab')2 fragment: preclinical evaluation of a potential construct for the targeted radiotherapy of malignant glioma

International Nuclear Information System (INIS)

Boskovitz, Abraham; Akabani, Gamal H.; Pegram, Charles N.; Bigner, Darrell D.; Zalutsky, Michael R.

2004-01-01

We have obtained encouraging responses in recent Phase I studies evaluating 131 I-labeled human/murine chimeric 81C6 anti-tenascin monoclonal antibody (ch81C6) administered into surgically-created tumor resection cavities in brain tumor patients. However, because the blood clearance is slow, hematologic toxicity has been higher than seen with murine 81C6 (mu81C6). In the current study, a series of paired-label experiments were performed in athymic mice bearing subcutaneous D-245 MG human glioma xenografts to compare the biodistribution of the fragment ch81C6 F(ab') 2 labeled using Iodogen to a) intact ch81C6, b) mu81C6, and c) ch81C6 F(ab') 2 labeled using N-succinimidyl 3-[ 131 I]iodobenzoate. Tumor retention of radioiodine activity for the F(ab') 2 fragment was comparable to that for intact ch81C6 for the first 24 h and to that for mu81C6 for the first 48 h; as expected, blood and other normal tissue levels declined faster for ch81C6 F(ab') 2. Radiation dosimetry calculations suggest that 131 I-labeled ch81C6 F(ab') 2 may warrant further evaluation as a targeted radiotherapeutic for the treatment of brain tumors

Polymer fragmentation in extensional flow

Energy Technology Data Exchange (ETDEWEB)

Maroja, Armando M.; Oliveira, Fernando A.; Ciesla, Michal; Longa, Lech

2001-06-01

In this paper we present an analysis of fragmentation of dilute polymer solutions in extensional flow. The transition rate is investigated both from theoretical and computational approaches, where the existence of a Gaussian distribution for the breaking bonds has been controversial. We give as well an explanation for the low fragmentation frequency found in DNA experiments.

Cross sections and kinematics of proton induced fragmentation of carbon

International Nuclear Information System (INIS)

Streibel, T.; Roecher, H.; Huentrup, G.; Heinrich, W.

1997-01-01

Charge changing fragmentation cross sections for C at a proton energy of about 70 MeV were measured. The discrepancies between measurement and model predictions indicate the necessity of further investigations. We have also measured distributions of fragment emission angles which can be described using a model with a momentum transfer to the fragmenting nucleus. The developed model leads to predictions for momentum distributions of proton induced target fragments of C at small energies. (orig.)

Cross sections and kinematics of proton induced fragmentation of carbon

Energy Technology Data Exchange (ETDEWEB)

Streibel, T; Roecher, H; Huentrup, G; Heinrich, W [Siegen Univ. (Germany). Dept. of Physics

1997-09-01

Charge changing fragmentation cross sections for C at a proton energy of about 70 MeV were measured. The discrepancies between measurement and model predictions indicate the necessity of further investigations. We have also measured distributions of fragment emission angles which can be described using a model with a momentum transfer to the fragmenting nucleus. The developed model leads to predictions for momentum distributions of proton induced target fragments of C at small energies. (orig.)

On the emission of fast and slow target fragments from 84Kr-AgBr interactions at 0.95 GeV/A

International Nuclear Information System (INIS)

Bhattacharjee, B.; Mukhopadhyay, A.; Singh, V.; Tuli, S.K.; Sengupta, S.

2003-01-01

Multiplicity distributions of secondary charged particles coming out of 84 Kr-AgBr interaction at 0.95 GeV/A have been reported. Angular distributions of fast and slow target fragments have also been studied. The sharp forward peak in the angular distribution of knocked out protons has further been analyzed in the light of intermittency and scaled factorial moment

A new crystal structure fragment-based pharmacophore method for G protein-coupled receptors

DEFF Research Database (Denmark)

Fidom, Kimberley; Isberg, Vignir; Hauser, Alexander Sebastian

2015-01-01

and receptor residue pairs, from crystal structure complexes. We describe the procedure to collect a library with more than 250 fragments covering 29 residue positions within the generic transmembrane binding pocket. We describe how the library fragments are recombined and inferred to build pharmacophores...... for new targets. A validating retrospective virtual screening of histamine H1 and H3 receptor pharmacophores yielded area-under-the-curves of 0.88 and 0.82, respectively. The fragment-based method has the unique advantage that it can be applied to targets for which no (homologous) crystal structures...... or ligands are known. 47% of the class A G protein-coupled receptors can be targeted with at least four-element pharmacophores. The fragment libraries can also be used to grow known ligands or for rotamer refinement of homology models. Researchers can download the complete fragment library or a subset...

Study of actinides fission induced by multi-nucleon transfer reactions in inverse kinematics

International Nuclear Information System (INIS)

Derkx, X.

2010-10-01

The study of actinide fission encounters two major issues. On one hand, measurements of the fission fragment distributions and the fission probabilities allow a better understanding of the fission process itself and the discrimination among the models of nuclear structure and dynamics. On the other hand, new measurements are required to improve nuclear data bases, which are a key component for the design of new generation reactors and radio-toxic waste incinerators. This thesis is in line with different French and American experimental projects using the surrogate method, i.e. transfer reactions leading to the same compound nuclei as in neutron irradiation, allowing the study of fission of actinides which are inaccessible by conventional techniques, whereas they are important for applications. The experiment is based on multi-nucleon transfer reactions between a 238 U beam and a 12 C target, using the inverse kinematics technique to measure, for each transfer channel, the complete isotopic distributions of the fission fragments with the VAMOS spectrometer. The work presented in this dissertation is focused on the identification of the transfer channels and their properties, as their angular distributions and the distributions of the associated excitation energy, using the SPIDER telescope to identify the target recoil nuclei. This work of an exploratory nature aims to generalize the surrogate method to heavy transfers and to measure, for the first time, the fission probabilities in inverse kinematics. The obtained results are compared with available direct kinematics and neutron irradiation measurements. (author)

Densities and temperatures at fragment formation in heavy-ion collision

Energy Technology Data Exchange (ETDEWEB)

Ohnishi, Akira [Hokkaido Univ., Sapporo (Japan)

1998-07-01

In order to clarify whether the liquid-gas phase transition is relevant to the multi-fragment formation found in intermediate energy heavy-ion collisions, we estimate the densities and temperatures at fragment formation in Au+Au collisions at incident energies of 150 MeV/A and 400 MeV/A within the Quantum Molecular Dynamics (QMD) model with and without quantum fluctuations implemented according to the Quantal Langevin (QL) model. The calculated results show that the IMFs are mainly produced inside the unstable region of nuclear matter, which supports the idea of the fragment formation from supercooled nuclear matter. (author)

MaRaCluster: A Fragment Rarity Metric for Clustering Fragment Spectra in Shotgun Proteomics.

Science.gov (United States)

The, Matthew; Käll, Lukas

2016-03-04

Shotgun proteomics experiments generate large amounts of fragment spectra as primary data, normally with high redundancy between and within experiments. Here, we have devised a clustering technique to identify fragment spectra stemming from the same species of peptide. This is a powerful alternative method to traditional search engines for analyzing spectra, specifically useful for larger scale mass spectrometry studies. As an aid in this process, we propose a distance calculation relying on the rarity of experimental fragment peaks, following the intuition that peaks shared by only a few spectra offer more evidence than peaks shared by a large number of spectra. We used this distance calculation and a complete-linkage scheme to cluster data from a recent large-scale mass spectrometry-based study. The clusterings produced by our method have up to 40% more identified peptides for their consensus spectra compared to those produced by the previous state-of-the-art method. We see that our method would advance the construction of spectral libraries as well as serve as a tool for mining large sets of fragment spectra. The source code and Ubuntu binary packages are available at https://github.com/statisticalbiotechnology/maracluster (under an Apache 2.0 license).

Plasma wake and nuclear forces on fragmented H+ transport

International Nuclear Information System (INIS)

Barriga-Carrasco, Manuel D; Deutsch, Claude

2006-01-01

The objective of the present work is to study the target electronic and nuclear interactions produced when a H + ion traverses classical plasma matter. Electronic interactions are treated by means of the dielectric formalism while nuclear interactions are dealt within the classical dispersion theory through a Monte Carlo computer code. The interactions through plasma electronic medium among close ions are called wake forces. We checked that these forces screen the Coulomb explosions of the two fragmented protons from the same H + ion decreasing their relative distance in the analysed cases. These forces align the interproton vector along the motion direction. They also tend the two-proton energy loss to the value of two isolated protons when at early times it is rather larger. Nevertheless most parts of these wake effects cannot be corroborated experimentally as they are masked by the projectile collisions with target nuclei in our numerical experiment. These collisions cancel the screening produced by the wake forces, increasing the interproton distance even faster than for bare Coulomb explosion. Also they misalign the interproton vector along the motion direction and contribute moderately to increase the energy loss of the fragmented H + ion. These nuclear collisions effects are more significant in reducing projectile velocity

Rayleigh-Taylor instability in multi-structured spherical targets

International Nuclear Information System (INIS)

Gupta, N.K.; Lawande, S.V.

1986-01-01

An eigenvalue equation for the exponential growth rate of the Rayleigh-Taylor instability is derived in spherical geometry. The free surface and jump boundary conditions are obtained from the eigenvalue equation. The eigenvalue equation is solved in the cases where the initial fluid density profile has a step function or exponential variation in space and analytical formulae for growth rate of the instability are obtained. The solutions for the step function are generalized for any number N of spherical zones forming an arbitrary fluid density profile. The results of the numerical calculations for N spherical zones are compared with the exact analytical results for exponential fluid density profile with N=10 and a good agreement is observed. The formalism is further used to study the effects of density gradients on Rayleigh-Taylor instability in spherical geometry. Also analytical formulae are presented for a particular case of N=3 and shell targets. The formalism developed here can be used to study the growth of the instability in present day multi-structured shell targets. (author)

Polarization and alignment of nucleus fission fragments

International Nuclear Information System (INIS)

Barabanov, A.L.; Grechukhin, D.P.

1987-01-01

Correlation of fragment orientation with orientation axis of fissile nucleus and with n-vector f vector of fragment divergence is considered. Estimations of polarization and alignment of fission fragments of preliminarily oriented nuclei in correlation (with n-vector f recording) and integral (with n-vector f averaging) experiments were conducted. It is shown that high sensitivity of polarization and fragment alignment to the character of nucleus movement at the stage of descent from barrier to rupture point exists

Ablation mass features in multi-pulses femtosecond laser ablate molybdenum target

Science.gov (United States)

Zhao, Dongye; Gierse, Niels; Wegner, Julian; Pretzler, Georg; Oelmann, Jannis; Brezinsek, Sebastijan; Liang, Yunfeng; Neubauer, Olaf; Rasinski, Marcin; Linsmeier, Christian; Ding, Hongbin

2018-03-01

In this study, the ablation mass features related to reflectivity of bulk Molybdenum (Mo) were investigated by a Ti: Sa 6 fs laser pulse at central wavelength 790 nm. The ablated mass removal was determined using Confocal Microscopy (CM) technique. The surface reflectivity was calibrated and measured by a Lambda 950 spectrophotometer as well as a CCD camera during laser ablation. The ablation mass loss per pulse increase with the increasing of laser shots, meanwhile the surface reflectivity decrease. The multi-pulses (100 shots) ablation threshold of Mo was determined to be 0.15 J/cm2. The incubation coefficient was estimated as 0.835. The reflectivity change of the Mo target surface following multi-pulses laser ablation were studied as a function of laser ablation shots at various laser fluences from 1.07 J/cm2 to 36.23 J/cm2. The results of measured reflectivity indicate that surface reflectivity of Mo target has a significant decline in the first 3-laser pulses at the various fluences. These results are important for developing a quantitative analysis model for laser induced ablation and laser induced breakdown spectroscopy for the first wall diagnosis of EAST tokamak.

Quantum Hall Effect: proposed multi-electron tunneling experiment

International Nuclear Information System (INIS)

Kostadinov, I.Z.

1985-11-01

Here we propose a tunneling experiment for the fractional and Integral Quantum Hall Effect. It may demonstrate multi-electron tunneling and may provide information about the nature of the macroscopic quantum states of 2D electronic liquid or solid. (author)

A shared experience of fragmentation: making sense of foster placement breakdown.

Science.gov (United States)

Rostill-Brookes, Helen; Larkin, Michael; Toms, Amy; Churchman, Clare

2011-01-01

Multiple placement transitions have been associated with poorer psychosocial outcomes for children growing up in local authority care. However, although there is an expanding literature examining the risk and protective factors connected with placement breakdown, very few studies have explored the quality of the move experience for those most closely involved with it. Our study considered how young people, foster carers and social workers made sense of unplanned placements' endings. Bringing together the lived experiences of these key stakeholders in the placement system added a novel dimension to existing research knowledge. What emerged from our analysis was evidence of a pervasive and shared emotional experience; all of the participants were affected by the breakdown irrespective of age, experience, or professional role. However, despite many commonalities, there was also a strong sense of fragmentation between the groups, which was characterised by discourses of mistrust and miscommunication. This meant that emotional reactions to the breakdown were often suppressed or dismissed, resentments built-up and attempts to find a solution were thwarted by silence or angry recrimination. These findings raise real challenges for practice and policy development. In particular, they stress the importance of shared and meaningful dialogue between all key stakeholders within the social care system, the need for more effective and timely support when placements are in crisis and opportunities for those most closely involved with the placement breakdown to process the emotional experience.

Jet reconstruction and measurement of identified fragmentation functions in Pb-Pb and pp collisions with the ALICE experiment

Energy Technology Data Exchange (ETDEWEB)

Lu, Xianguo; Busch, Oliver [Physikalisches Institut, Heidelberg (Germany); Collaboration: ALICE-Collaboration

2014-07-01

Jets are defined in QCD as cascades of consecutive emission of partons from an initial hard scattering. The process of parton showering and subsequent hadronisation is broadly known as fragmentation. High energy nucleus-nucleus collisions allow us to probe parton fragmentation within a QCD medium and the properties of this medium via the modification of the jet spectrum and jet structure. Jet reconstruction in pp collisions provides an elementary baseline and allows to investigate perturbative and non-perturbative aspects of particle production. In addition to inclusive probes, identified particles in the final states provide an enhanced sensitivity to the flavor dependence of fragmentation and nuclear modifications. ALICE at the CERN LHC is a general-purpose heavy ion experiment designed to study the physics of strongly interacting matter and the Quark-Gluon-Plasma. It has an excellent tracking and particle identification performance over a wide momentum range. In this talk we present results on inclusive jet observable as well as the novel measurements of identified fragmentation functions in pp and Pb-Pb collisions. The results are confronted with theory predictions.

Multi-scale Regions from Edge Fragments

DEFF Research Database (Denmark)

Kazmi, Wajahat; Andersen, Hans Jørgen

2014-01-01

In this article we introduce a novel method for detecting multi-scale salient regions around edges using a graph based image compression algorithm. Images are recursively decomposed into triangles arranged into a binary tree using linear interpolation. The entropy of any local region of the image......), their performance is comparable to SIFT (Lowe, 2004).We also show that when they are used together with MSERs (Matas et al., 2002), the performance of MSERs is boosted....

Fission fragment angular momentum

International Nuclear Information System (INIS)

Frenne, D. De

1991-01-01

Most of the energy released in fission is converted into translational kinetic energy of the fragments. The remaining excitation energy will be distributed among neutrons and gammas. An important parameter characterizing the scission configuration is the primary angular momentum of the nascent fragments. Neutron emission is not expected to decrease the spin of the fragments by more than one unit of angular momentum and is as such of less importance in the determination of the initial fragment spins. Gamma emission is a suitable tool in studying initial fragment spins because the emission time, number, energy, and multipolarity of the gammas strongly depend on the value of the primary angular momentum. The main conclusions of experiments on gamma emission were that the initial angular momentum of the fragments is large compared to the ground state spin and oriented perpendicular to the fission axis. Most of the recent information concerning initial fragment spin distributions comes from the measurement of isomeric ratios for isomeric pairs produced in fission. Although in nearly every mass chain isomers are known, only a small number are suitable for initial fission fragment spin studies. Yield and half-life considerations strongly limit the number of candidates. This has the advantage that the behavior of a specific isomeric pair can be investigated for a number of fissioning systems at different excitation energies of the fragments and fissioning nuclei. Because most of the recent information on primary angular momenta comes from measurements of isomeric ratios, the global deexcitation process of the fragments and the calculation of the initial fragment spin distribution from measured isomeric ratios are discussed here. The most important results on primary angular momentum determinations are reviewed and some theoretical approaches are given. 45 refs., 7 figs., 2 tabs

Multi-targeted and aggressive treatment of patients with type 2 diabetes at high risk

DEFF Research Database (Denmark)

Gaede, P; Pedersen, O

2005-01-01

Results from many single risk factor intervention trials and the multi-targeted Steno-2 trial in the last few years have provided a strong case that management of type 2 diabetes in all age groups requires a structured and intensified approach that is far more than just glucocentric, an approach...... addressing additional cardiovascular risk factors including hypertension, dyslipidaemia, sedentary behaviour, smoking and dietary habits causing insulin resistance and pro-inflammation. This type of integrated therapy applied for almost 8 years to high-risk type 2 diabetic patients has cut the relative risk......-driven polypharmacy and simple but focused behaviour modelling with continuous education, motivation and trouble-shooting for treatment barriers identified for the patient and the care giver. It is high time we transfer these experiences and major health benefits gained in the 'green house' of controlled clinical...

Fragmentation of 400 MeV/u {sup 12}C on a thin graphite target

Energy Technology Data Exchange (ETDEWEB)

Schuy, Christoph

2015-07-01

Detailed understanding of high energetic heavy ions interacting with matter is of great interest in basic research and applied physics especially in radiotherapy and space radioprotection. Radiotherapy with carbon ions showed great success especially in the treatment of deep seated tumors due to the favorable depth-dose profile and increased biological effectiveness compared to photons or protons. Due to nuclear interactions between the primary beam and the patient's body, usually only 50% of the carbon ions will reach the target location. Thus, a detailed knowledge of the changes in the radiation field is required for delivering a successful treatment. The radiation environment in space is composed of high energy charged particles and can lead to serious health risks for astronauts. The assessment and mitigation of radioinduced health complications cannot be accomplished without a good understanding of the interaction of the mixed radiation field with e.g. the hull of the spaceship or lunar soil. In this work the fragmentation of 400 MeV/u {sup 12}C on a thin graphite target was investigated. The resulting angular yield distributions and differential energy spectra of charged and uncharged particles are presented and compared to two different Monte Carlo codes (PHITS and GEANT4).

Site Identification by Ligand Competitive Saturation (SILCS) simulations for fragment-based drug design.

Science.gov (United States)

Faller, Christina E; Raman, E Prabhu; MacKerell, Alexander D; Guvench, Olgun

2015-01-01

Fragment-based drug design (FBDD) involves screening low molecular weight molecules ("fragments") that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind nonoverlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR and X-ray crystallography, have proven very useful but can be expensive in terms of time, materials, and labor. Accordingly, a variety of computational FBDD approaches have been developed that provide different levels of detail and accuracy.The Site Identification by Ligand Competitive Saturation (SILCS) method of computational FBDD uses all-atom explicit-solvent molecular dynamics (MD) simulations to identify fragment binding. The target is "soaked" in an aqueous solution with multiple fragments having different identities. The resulting computational competition assay reveals what small molecule types are most likely to bind which regions of the target. From SILCS simulations, 3D probability maps of fragment binding called "FragMaps" can be produced. Based on the probabilities relative to bulk, SILCS FragMaps can be used to determine "Grid Free Energies (GFEs)," which provide per-atom contributions to fragment binding affinities. For essentially no additional computational overhead relative to the production of the FragMaps, GFEs can be used to compute Ligand Grid Free Energies (LGFEs) for arbitrarily complex molecules, and these LGFEs can be used to rank-order the molecules in accordance with binding affinities.

Religious Fragmentation, Social Identity and Conflict: Evidence from an Artefactual Field Experiment in India.

Science.gov (United States)

Chakravarty, Surajeet; Fonseca, Miguel A; Ghosh, Sudeep; Marjit, Sugata

2016-01-01

We examine the impact of religious identity and village-level religious fragmentation on behavior in Tullock contests. We report on a series of two-player Tullock contest experiments conducted on a sample of 516 Hindu and Muslim participants in rural West Bengal, India. Our treatments are the identity of the two players and the degree of religious fragmentation in the village where subjects reside. Our main finding is that the effect of social identity is small and inconsistent across the two religious groups in our study. While we find small but statistically significant results in line with our hypotheses in the Hindu sample, we find no statistically significant effects in the Muslim sample. This is in contrast to evidence from Chakravarty et al. (2016), who report significant differences in cooperation levels in prisoners' dilemma and stag hunt games, both in terms of village composition and identity. We attribute this to the fact that social identity may have a more powerful effect on cooperation than on conflict.

Fragmentation in 28Si-emulsion interactions at 3.7A GeV

International Nuclear Information System (INIS)

Singh, B.K.; Tuli, S.K.

1999-01-01

The results on fragmentation of a 3.7A GeV 28 Si projectile in interactions with different target nuclei in nuclear emulsion are presented. Limiting fragmentation behaviour of the projectile fragments is achieved at this energy. It is shown that the factorization principle for fragmentation cross-sections holds for light fragments only. A bond percolation prescription is able to reproduce the experimental observations for fragments with charge 4≤Z≤10. A rise in the production of helium fragments is also predicted by bond percolation

Inorganic nanocomposite films with polymer nanofillers made by the concurrent multi-beam multi-target pulsed laser deposition

Science.gov (United States)

Darwish, Abdalla M.; Sarkisov, Sergey S.; Mele, Paolo; Saini, Shrikant; Moore, Shaelynn; Bastian, Tyler; Dorlus, Wydglif; Zhang, Xiaodong; Koplitz, Brent

2017-08-01

We report on the new class of inorganic nanocomposite films with the inorganic phase hosting the polymer nanofillers made by the concurrent multi-beam multi-target pulsed laser deposition of the inorganic target material and matrix assisted pulsed laser evaporation of the polymer (MBMT-PLD/MAPLE). We used the exemplary nanocomposite thermoelectric films of aluminum-doped ZnO known as AZO with the nanofillers made of poly(methyl methacrylate) known as PMMA on various substrates such as SrTiO3, sapphire, fused silica, and polyimide. The AZO target was ablated with the second harmonic (532 nm) of the Nd:YAG Q-switched laser while PMMA was evaporated from its solution in chlorobenzene frozen in liquid nitrogen with the fundamental harmonic (1064 nm) of the same laser (50 Hz pulse repetition rate). The introduction of the polymer nanofillers increased the electrical conductivity of the nanocomposite films (possibly due to the carbonization of PMMA and the creation of additional channels of electric current) three times and reduced the thermal conductivity by 1.25 times as compared to the pure AZO films. Accordingly, the increase of the thermoelectric figure-of merit ZT would be 4 times. The best performance was observed for the sapphire substrates where the films were the most uniform. The results point to a huge potential of the optimization of a broad variety of optical, opto-electronic, and solar-power nanocomposite inorganic films by the controllable introduction of the polymer nanofillers using the MBMT-PLD/MAPLE method.

Fragmentation of CO{sub 2} into C{sup +} + O{sup +} + O, in collisions with protons

Energy Technology Data Exchange (ETDEWEB)

Moretto-Capelle, P. [Laboratoire CAR-IRSAMC, UMR 5589 CNRS-Universite Paul Sabatier, 118 rue de Narbonne, 31062 Toulouse Cedex (France). E-mail: pmc at yosemite.ups-tlse.fr; Bordenave-Montesquieu, D.; Bordenave-Montesquieu, A. [Laboratoire CAR-IRSAMC, UMR 5589 CNRS-Universite Paul Sabatier, 118 rue de Narbonne, 31062 Toulouse Cedex (France)

2000-08-14

The fragmentation of CO{sub 2} has been investigated in 25 keV H{sup +} + CO{sub 2} collisions using an electron-ion-ion triple coincidence technique. In this letter we focus on the three-body fragmentation into the C{sup +} + O{sup +} + O final state. A comparison between the measured correlation of C{sup +},O{sup +} and O momenta and simple kinematic models allows us to demonstrate that in the present case, a rather unexpected two-step process with formation of a CO{sup 2+} ion as an intermediate state occurs. This result is at variance with the conclusions of other authors achieved in collisions of photons and electrons with the dioxide molecule. Kinetic energy release distributions in the two steps of the dissociation process are also deduced from experiment; the distributions found for the fragmentation of CO{sup 2+} into C{sup +} + O{sup +} are found to be very similar to those measured by other authors in collisions of various particles (photons, multi-charged ions) with CO molecules at high enough collision energy. (author). Letter-to-the-editor.

Tracking considerations for fixed target B experiments at SSC and LHC

International Nuclear Information System (INIS)

McManus, A.P.; Conetti, S.; Corti, G.; Cox, B.; Dukes, E.C.; Lawry, T.; Nelson, K.; Tzamouranis, I.

1993-01-01

Fixed target beauty (B) experiments proposed at the SSC or LHC come in two basic types. Extracted beam experiments use a bent crystal of silicon or some other method to extract a beam of protons parasitically from the circulating beam as the collider experiments are taking data. The two chief extracted beam experiments are the LHB collaboration at the LHC and the SFT collaboration at the SSC. The second type of fixed target experiment places the detector around the circulating beam using a gas jet or thin wire(s) as a target. The (GAJET) experiment proposed at CERN for LHC and the Hera-B experiment at DESY are of this type

Tumour targeting with monovalent fragments of anti-neuroblastoma antibody chCE7

International Nuclear Information System (INIS)

Carrel, F.; Novak-Hofer, I.; Ruch, C.; Zimmermann, K.; Amstutz, H.

1997-01-01

The in vitro and in vivo behaviour of the monovalent single chain (scFv) and Fab-fragments derived from anti-neuroblastoma antibody chCE7 is reported. When comparing tumour uptake and -retention of radioactivity of 67 Cu-labelled monovalent chCE7 with divalent chCE7 F(ab') 2 the advantage of the radiocopper label over the radioiodine label was more pronounced with the divalent (internalising) F(ab') 2 fragments. (author) 1 fig., 1 ref

Optimized swimmer tracking system based on a novel multi-related-targets approach